There are 40 clinical trials

Clinical Trials

1 A Phase 2 Study of Trastuzumab in Combination With BMS-247550 in Women With Metastatic Breast Cancer

This phase II trial is studying how well giving trastuzumab together with ixabepilone works in treating women with HER2-positive metastatic breast cancer. Monoclonal antibodies, such as trastuzumab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining trastuzumab with ixabepilone may kill more tumor cells.

NCT00079326 HER2-positive Breast Cancer Recurrent Breast Cancer Stage IV Breast Cancer Biological: trastuzumab Drug: ixabepilone Other: laboratory biomarker analysis

MeSH:Breast Neoplasms

HPO:Breast carcinoma Neoplasm of the breast

HER2/phospho-HER2, EGFR/phospho-EGFR, IGRF-I, phospho-MAPK, phospho-P13K, bcl-2, bcl-xL, MDR-1, MRP and β-tubulin) and blood biomarkers (HER2-extracellular domain [ECD], circulating tumor cells) to correlate them with response to treatment. --- P13K ---

2 Phase I/II Trial of ZD1839 (Iressa®), Trastuzumab (Herceptin®), and Docetaxel (Taxotere®) in Patients With erbB-2 (HER-2) Overexpressing, Stage IV Breast Carcinoma

RATIONALE: Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining gefitinib and trastuzumab with docetaxel may kill more tumor cells. PURPOSE: This phase I/II trial is studying the best dose of docetaxel when given together with gefitinib and trastuzumab in treating patients with metastatic breast cancer.

NCT00086957 Breast Cancer Biological: trastuzumab Drug: docetaxel Drug: gefitinib

MeSH:Breast Neoplasms

HPO:Breast carcinoma Neoplasm of the breast

- Correlate expression and/or degree of phosphorylation of epidermal growth factor receptor, HER2/neu, c-fos, Akt, ERK½, P13K, p53, p21, and p27 with outcome in patients treated with this regimen. --- P13K ---

3 Phase II Evaluation of Cetuximab (C225) Combined With Induction Paclitaxel and Carboplatin Followed by C225, Paclitaxel, Carboplatin, and Radiation for Stage III/IV Operable Squamous Cancer of the Head and Neck

RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving cetuximab with combination chemotherapy and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving cetuximab after surgery may kill any tumor cells that remain. PURPOSE: This phase II trial is studying how well giving cetuximab together with combination chemotherapy and radiation therapy works in treating patients who are undergoing surgery for stage III or stage IV head and neck cancer.

NCT00089297 Head and Neck Cancer Biological: Cetuximab Drug: Carboplatin Drug: Paclitaxel Radiation: Radiation therapy

MeSH:Head and Neck Neoplasms

HPO:Neoplasm of head and neck

- Determine the effect of this treatment regimen on selective biologic pathways, total and phosphorylated epidermal growth factor receptor, ERK/MAPK, and P13K/AKT in these patients. --- P13K ---

4 Phase I, Pharmacokinetic and Pharmacodynamic Study of BAY 43-9006 (Sorafenib) in Combination With CCI-779 (Temsirolimus) in Advanced Solid Malignancies

This phase I trial is studying the side effects and best dose of temsirolimus when given together with sorafenib in treating patients with unresectable or metastatic solid tumors. Sorafenib and temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving sorafenib together with temsirolimus may kill more tumor cells.

NCT00255658 Unspecified Adult Solid Tumor, Protocol Specific Drug: sorafenib tosylate Drug: temsirolimus Other: laboratory biomarker analysis

To analyze the biologic effects of BAY 43-9006 and CCI-779 on downstream targets of the P13K/Akt/mTOR and Raf signaling pathways. --- P13K ---

5 A Phase II Trial of Adjuvant Paclitaxel and Trastuzumab for Node-Negative HER2-Positive Breast Cancer

The purpose of this study is to find out what effect the postoperative combination of therapies: trastuzumab (herceptin) and paclitaxel (taxol) will have on breast cancer recurrence. A combination of trastuzuamb and chemotherapy has been used in women with node positive and high risk node negative disease. This tests utilizes a well tolerated regimen of weekly paclitaxel and trastuzumab in women with T1, node negative tumors that are HER2 positive. We would like to determine how effective this drug combination is when used in women with early stage breast cancer, as well as to better define the side effects of this treatment.

NCT00542451 Breast Cancer Carcinoma of the Breast Drug: Paclitaxel Drug: Trastuzumab

MeSH:Breast Neoplasms

HPO:Breast carcinoma Neoplasm of the breast

Evaluate P13K mutations and PTEN alterations in a subset of patients and correlate events with the presence or absence of these mutations/alterations. --- P13K ---

6 A Phase I and Randomized Phase II Trial of Gemcitabine + Erlotinib (NSC-718781) + IMC-A12 (NSC-742460) vs. Gemcitabine + Erlotinib as First-Line Treatment in Patients With Metastatic Pancreatic Cancer

This randomized phase I/II trial is studying the side effects and best dose of monoclonal antibody therapy when given together with gemcitabine hydrochloride and erlotinib hydrochloride and to see how well they work compared with giving gemcitabine hydrochloride and erlotinib hydrochloride alone as first-line therapy in treating patients with metastatic pancreatic cancer that cannot be removed by surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving erlotinib hydrochloride and gemcitabine hydrochloride together with monoclonal antibody therapy may kill more tumor cells.

NCT00617708 Stage IV Pancreatic Cancer Biological: cixutumumab Drug: erlotinib hydrochloride Drug: gemcitabine hydrochloride

MeSH:Pancreatic Neoplasms

HPO:Neoplasm of the pancreas

Samples are assessed for the potential relationship between gene expression levels, germline polymorphisms, Ras and P13K mutations and progression-free survival and overall survival. --- P13K ---

7 A Phase III Randomized Trial of Metformin Versus Placebo on Recurrence and Survival in Early Stage Breast Cancer

This study is looking at whether Metformin, an agent that is commonly used to treat diabetes, can decrease or affect the ability of breast cancer cells to grow and whether Metformin will work with other therapies to keep cancer from recurring. Health Canada has not approved the sale or use of Metformin to treat breast cancer, although they have approved its use in this clinical trial. Although Metformin is approved by the FDA for the treatment of diabetes, its use in breast cancer is considered investigational.

NCT01101438 Breast Cancer Drug: metformin hydrochloride Other: placebo

MeSH:Breast Neoplasms

HPO:Breast carcinoma Neoplasm of the breast

- Concurrent or planned participation in randomized trials of weight loss or exercise interventions or trials targeting insulin, IGF-1 or their receptors, or involving P13K inhibitors (at the time of randomization)*. --- P13K ---

8 A Phase II Study of MK-2206 in the Treatment of Recurrent High-Grade Serous Platinum-Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Akt inhibitor MK2206 is a drug that may stop cancer cells from growing by blocking a protein called protein kinase B (AKT) inside the cell. AKT interacts with other proteins in the cell that are part of the P13K/AKT pathway, a pathway that is know to play a role in the growth of cancer cells. Mutations in P13K or in AKT, or changes in another protein called phosphatase and tensin homolog (PTEN) in this pathway can lead it to become more active than is normal. This study investigates how effective MK-2206 is in treating ovarian, fallopian tube, or primary peritoneal cancer where there are mutations in P13K or AKT or low levels of PTEN.

NCT01283035 Ovarian Sarcoma Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma Drug: Akt Inhibitor MK2206 Other: Laboratory Biomarker Analysis

MeSH:Carcinoma

HPO:Carcinoma

AKT interacts with other proteins in the cell that are part of the P13K/AKT pathway, a pathway that is know to play a role in the growth of cancer cells. --- P13K ---

Mutations in P13K or in AKT, or changes in another protein called phosphatase and tensin homolog (PTEN) in this pathway can lead it to become more active than is normal. --- P13K ---

This study investigates how effective MK-2206 is in treating ovarian, fallopian tube, or primary peritoneal cancer where there are mutations in P13K or AKT or low levels of PTEN. --- P13K ---

9 A Phase I Study of Bevacizumab and Escalation Doses of BKM-120 in Patients With Metastatic Renal Cell Carcinoma Who Failed Prior Systemic Therapies

BKM-120 is a drug that may slow the growth of cancer cells. This drug has been used in laboratory experiments and information from those research studies suggests that this drug may help to slow the growth of renal cancer cells. In this research study, the investigators are testing the safety to BKM-120 at different dose levels. The investigators will also be studying how well tolerated BKM-120 is, and how effective BKM-120 can be in the treatment of kidney cancer.

NCT01283048 Renal Cell Carcinoma Drug: BKM-120 Bevacizumab

MeSH:Carcinoma Carcinoma, Renal Cell

HPO:Carcinoma Clear cell renal cell carcinoma Papillary renal cell carcinoma Renal cell carcinoma

Inclusion Criteria: - Metastatic RCC with clear cell component or papillary RCC - Life expectancy > 12 weeks - Must have failed at least 1 prior anti-VEGF systemic therapy for metastatic RCC Exclusion Criteria: - Prior treatment with a P13K inhibitor or bevacizumab - Untreated brain metastases - Acute or chronic liver or pancreatic disease - Major mood disorder - Concurrent severe and/or uncontrolled medical condition - Diabetes mellitus - GI disease - Currently taking therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulant - Pregnant or breastfeeding - HIV positive - History of another malignancy within 3 years except cured basal cell carcinoma of the skin or excised in situ carcinoma of the cervix - Uncontrolled hypertension Inclusion Criteria: - Metastatic RCC with clear cell component or papillary RCC - Life expectancy > 12 weeks - Must have failed at least 1 prior anti-VEGF systemic therapy for metastatic RCC Exclusion Criteria: - Prior treatment with a P13K inhibitor or bevacizumab - Untreated brain metastases - Acute or chronic liver or pancreatic disease - Major mood disorder - Concurrent severe and/or uncontrolled medical condition - Diabetes mellitus - GI disease - Currently taking therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulant - Pregnant or breastfeeding - HIV positive - History of another malignancy within 3 years except cured basal cell carcinoma of the skin or excised in situ carcinoma of the cervix - Uncontrolled hypertension Renal Cell Carcinoma Carcinoma Carcinoma, Renal Cell Subjects will receive an intravenous infusion of Avastin on Day 1 and Day 15 of each month (cycle). --- P13K ---

Inclusion Criteria: - Metastatic RCC with clear cell component or papillary RCC - Life expectancy > 12 weeks - Must have failed at least 1 prior anti-VEGF systemic therapy for metastatic RCC Exclusion Criteria: - Prior treatment with a P13K inhibitor or bevacizumab - Untreated brain metastases - Acute or chronic liver or pancreatic disease - Major mood disorder - Concurrent severe and/or uncontrolled medical condition - Diabetes mellitus - GI disease - Currently taking therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulant - Pregnant or breastfeeding - HIV positive - History of another malignancy within 3 years except cured basal cell carcinoma of the skin or excised in situ carcinoma of the cervix - Uncontrolled hypertension Inclusion Criteria: - Metastatic RCC with clear cell component or papillary RCC - Life expectancy > 12 weeks - Must have failed at least 1 prior anti-VEGF systemic therapy for metastatic RCC Exclusion Criteria: - Prior treatment with a P13K inhibitor or bevacizumab - Untreated brain metastases - Acute or chronic liver or pancreatic disease - Major mood disorder - Concurrent severe and/or uncontrolled medical condition - Diabetes mellitus - GI disease - Currently taking therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulant - Pregnant or breastfeeding - HIV positive - History of another malignancy within 3 years except cured basal cell carcinoma of the skin or excised in situ carcinoma of the cervix - Uncontrolled hypertension Renal Cell Carcinoma Carcinoma Carcinoma, Renal Cell Subjects will receive an intravenous infusion of Avastin on Day 1 and Day 15 of each month (cycle). --- P13K --- --- P13K ---

10 A Phase I Study of BKM120 + Carboplatin + Paclitaxel for Patients With Advanced Solid Tumors

The purpose of this study is to find out the good and bad effects that occur when BKM120 is added to standard chemotherapy with carboplatin and paclitaxel.

NCT01297452 Solid Tumors Drug: BKM120 days 1 - 21 plus paclitaxel + carboplatin Drug: BKM120 (days 1 - 28, ) plus paclitaxel + carboplatin Drug: BKM120 (days 1-21) + paclitaxel (day 1) + carboplatin (day 1) Drug: BKM120, Paclitaxel + Carboplatin

MeSH:Neoplasms

HPO:Neoplasm

Exclusion Criteria: - Patients who have received prior treatment with a P13K inhibitor. --- P13K ---

11 A Phase I Trial of Irinotecan and BKM120 in Previously Treated Advanced Colorectal Cancer

This phase I trial will use the combination of irinotecan and BKM120 in patients with advanced colorectal cancer who have failed on or have become intolerant of at least one line of therapy for advanced colorectal cancer and who are candidates for irinotecan therapy.

NCT01304602 Colorectal Cancer Drug: Irinotecan Drug: BKM120

MeSH:Colorectal Neoplasms

HPO:Neoplasm of the large intestine

If clinically indicated, pulmonary function tests including measures of predicted lung volumes, DLco, O2 saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates - Clinical manifestation of diabetes mellitus or steroid-induced diabetes mellitus - Impairment of GI function or disease that may significantly alter the absorption of BKM120; diarrhea ≥ grade 2 - Major surgery ≤ 4 weeks prior to starting study drug - Prior treatment with a P13K inhibitor; any hematopoietic colony-stimulating growth factors ≤ 2 weeks prior to starting study drug; corticosteroids ≤ 2 weeks prior to starting study drug; chemotherapy or targeted anticancer therapy ≤4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug; small molecule therapeutics (excluding monoclonal antibodies) ≤5 effective half-lives prior to starting study drug - Currently receiving medication that has the potential to prolong the QT interval or inducing Torsades de Pointes - chronic treatment with steroids or another immunosuppressive agent. --- P13K ---

12 A Phase II Study of BKM 120 for Patients With Recurrent Glioblastoma and Activated PI3K Pathway

BKM120 is a newly discovered drug that has been used in other research studies. Information from those other research studies suggests that BKM120 may help to slow or stop the growth of malignant gliomas. The purpose of this study is to see how well BKM120 works in patients with malignant gliomas. Patients on this study will be treated in two groups: patients who are going to receive surgery and those who will not receive surgery. This study is trying to determine how effective BKM120 is in stopping cancer cells from growing. For patients receiving surgery the research will also try to determine if an effective level of BKM120 can penetrate the brain before surgery.

NCT01339052 Glioblastoma Drug: BKM120 Procedure: Surgery

MeSH:Glioblastoma

HPO:Glioblastoma multiforme

Exclusion Criteria: - Participants who have received prior treatment with a P13K inhibitor, AKT inhibitor, mTOR inhibitor (e.g. --- P13K ---

13 A Phase 1 Trial of BKM 120, a Novel Oral Selective Phosphatidylinositol-3-kinase (PI3K) Inhibitor, in Combination With Fulvestrant in Postmenopausal Women With Estrogen Receptor Positive Metastatic Breast Cancer

This phase I trial will determine the Maximum Tolerated Dose (MTD) of BKM120 when given together with fulvestrant in treating postmenopausal patients with estrogen receptor-positive (ER+) stage IV breast cancer. The toxicity profile of this combination therapy will also be described. Inhibition of PI3K by BKM120 may enhance programmed cell death (apoptosis) in estrogen receptor positive (ER+) breast cancer cells. Giving fulvestrant together with BKM 120 may enhance this apoptotic effect, providing a novel therapeutic strategy for patients with metastatic ER+ breast cancer.

NCT01339442 Estrogen Receptor-positive Breast Cancer Recurrent Breast Cancer Stage IV Breast Cancer Drug: BKM120 Drug: Fulvestrant Procedure: biopsy

MeSH:Breast Neoplasms

HPO:Breast carcinoma Neoplasm of the breast

Inclusion Criteria: - Patient must be ≥ 18 years of age - Patient must be a postmenopausal woman, defined by one of the following criteria: - Women ≥ 60 years - Women aged 45-59 years with spontaneous cessation of menses ≥ 12 months prior to registration - Women aged 45-59 years with cessation of menses of duration < 12 months or secondary to hysterectomy AND an follicle-stimulating hormone (FSH) level in the postmenopausal range according to institutional standards (or > 34.4 IU/L if institutional range is not available) prior to registration - Women aged 45-59 years on hormonal replacement therapy who have discontinued hormonal therapy AND an FSH level in the postmenopausal range according to institutional standards (or > 34.4 IU/L if institutional range is not available) prior to registration - Status post bilateral surgical oophorectomy - Patient must have a negative serum pregnancy test within 48 hours before starting study treatment (if a woman of childbearing potential) - Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2 - Patient must have histologically or cytologically confirmed invasive breast cancer that is stage IV or metastatic (histologic/cytologic confirmation of recurrence preferred, but not required) - Patient must have a representative tumor tissue specimen available; archival tissue is allowed - Either the primary or the metastatic tumor must be positive for estrogen receptor (>= 1% tumor cell staining by immunohistochemistry or an Allred Score of >= 3 by immunohistochemistry) - Patient must have at least one site of measurable disease as per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria - Patient must have had no more than 3 lines of systemic therapy (including endocrine therapy) for metastatic disease to be eligible for phase IB and the last 10 patients of Cohort C; there is no limitation on the numbers of prior systemic therapies for phase IA and the first 2 patients of Cohort C - Patients who are currently taking fulvestrant without disease progression are eligible - Patient must have a life expectancy of >= 12 weeks - Patient must have adequate oran function as defined as: - Absolute neutrophil count (ANC) >= 1500/uL - Platelet count >= 100,000/uL - Hemoglobin >= 9 g/dL - Serum creatinine =< 1.5 x upper limit of normal (ULN) - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range (or =< 3.0 x ULN if liver metastases are present) - Serum bilirubin =< ULN (or =< 1.5 x ULN if liver metastases are present; or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert Syndrome) - Serum amylase =< ULN - Serum lipase =< ULN - Magnesium >= the lower limit of normal - Potassium within normal limits for the institution - Patient must have international normalized ratio (INR) =< 2 - Patient must have fasting plasma glucose =< 120 mg/dL (6.7 mmol/L) - Patient must have total calcium (corrected for serum albumin) within normal limits (bisphosphonate use for malignant hypercalcemia control is not allowed) - Patient must be able and willing to sign the consent form Exclusion Criteria: - Patient must not have received prior treatment with a P13K inhibitor - Patient must not have a known hypersensitivity to BKM120 or to its excipients - Patient must not have untreated brain metastases; however, patients with metastatic central nervous system (CNS) tumors may participate in this trial if the patient is: - 4 weeks from therapy completion (including radiation and/or surgery) - Clinically stable at the time of study entry - Not receiving corticosteroid therapy - Patient must not have acute or chronic liver disease, renal disease, or pancreatitis - Patient must not have any of the following mood disorders as judged by the Investigator or a Psychiatrist - Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others) - Greater than or equal to Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety - Patient must not meet the cut-off score of >= 10 in the Patient Health Questionnaire (PHQ-9) or a cut-off of >= 15 in the Generalized Anxiety Disorder (GAD)-7 mood scale, respectively, or select a positive response of 1, 2, or 3 to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9) - Patient must not have >= grade 2 diarrhea - Patient must not have active cardiac disease including any of the following: - Left ventricular ejection fraction (LVEF) < 50% as determined by Multiple Grated acquisition (MUGA) scan or echocardiogram (ECHO) - QTc > 480 msec on screening electrocardiogram (ECG) (using the QTcF formula) - Angina pectoris that requires the use of anti-anginal medication - Ventricular arrhythmias except for benign premature ventricular contractions - Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication - Conduction abnormality requiring a pacemaker - Valvular disease with document compromise in cardiac function - Symptomatic pericarditis - Patient must not have a history of cardiac dysfunction including any of the following: - Myocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function - History of documented congestive heart failure (New York Heart Association functional classification III-IV) - Documented cardiomyopathy - Patient must not have poorly controlled diabetes mellitus or steroid-induced diabetes mellitus (defined by fasting glucose >120 mg/dL or hemoglobin [Hb] A1c > 7%) - Patient must not have any other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol - Patient must not have significant symptomatic deterioration of lung function; if clinically indicated, pulmonary function tests including measures of predicted lung volumes; diffusion capacity of carbon monoxide (DLco), oxygen (O2) saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates - Patient must not have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection); patients with unresolved diarrhea will be excluded as previously indicated - Patient must not have been treated with any hematopoietic colony-stimulating growth factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF]) =< 2 weeks prior to starting study drug; erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment, may be continued - Patient must not have taken herbal medications and certain fruits within 7 days prior to starting study drug; herbal medications include, but are not limited to: St. Johns wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng; fruits include the CYP3A inhibitors Seville oranges, grapefruit, pummelos, or exotic citrus fruits - Patient must not be currently receiving treatment with medication with a known risk to prolong the QT interval or inducing Torsades de Pointes unless the treatment can either be discontinued or switched to a different medication prior to starting study drug; please refer to Table 5-2 for a list of prohibited QT prolonging drugs with risk of Torsades de Pointes - Patient must not be receiving chronic treatment with steroids or another immunosuppressive agent; Note: topical applications (e.g. --- P13K ---

dexamethasone 2 mg/day, prednisolone 10 mg/day) for at least 14 days before start of study treatment are eligible - Patient must not be currently treated with drugs known to be moderate or strong inhibitors or inducers of isoenzyme cytochrome P450, family 3, subfamily A (CYP3A) unless the treatment can be discontinued or switched to a different medication prior to starting study drug (please note that co-treatment with weak inhibitors of CYP3A is allowed) - Patient must not have received chemotherapy or targeted anticancer therapy =< 4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug - Patient with any residual toxicities may not be enrolled unless all toxicities recover to =< grade 1 before starting the trial - Patient must not have received any continuous or intermittent small molecule therapeutics (excluding monoclonal antibodies) =< 5 effective half lives prior to starting study drug; patient must have recovered from side effects of such therapy - Patient must not have received wide field radiotherapy =< 4 weeks or limited field radiation for palliation =< 2 weeks prior to starting study drug; patient must have recovered from side effects of such therapy - Patient must not have undergone major surgery =< 2 weeks prior to starting study drug; patient must have recovered from side effects of such therapy - Patient must not be currently taking therapeutic doses of warfarin sodium or any other Coumadin-derivative anticoagulant - Patient must not have a known diagnosis of human immunodeficiency virus (HIV) infection - Patient must not have a history of another malignancy within 3 years, except cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix Inclusion Criteria: - Patient must be ≥ 18 years of age - Patient must be a postmenopausal woman, defined by one of the following criteria: - Women ≥ 60 years - Women aged 45-59 years with spontaneous cessation of menses ≥ 12 months prior to registration - Women aged 45-59 years with cessation of menses of duration < 12 months or secondary to hysterectomy AND an follicle-stimulating hormone (FSH) level in the postmenopausal range according to institutional standards (or > 34.4 IU/L if institutional range is not available) prior to registration - Women aged 45-59 years on hormonal replacement therapy who have discontinued hormonal therapy AND an FSH level in the postmenopausal range according to institutional standards (or > 34.4 IU/L if institutional range is not available) prior to registration - Status post bilateral surgical oophorectomy - Patient must have a negative serum pregnancy test within 48 hours before starting study treatment (if a woman of childbearing potential) - Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2 - Patient must have histologically or cytologically confirmed invasive breast cancer that is stage IV or metastatic (histologic/cytologic confirmation of recurrence preferred, but not required) - Patient must have a representative tumor tissue specimen available; archival tissue is allowed - Either the primary or the metastatic tumor must be positive for estrogen receptor (>= 1% tumor cell staining by immunohistochemistry or an Allred Score of >= 3 by immunohistochemistry) - Patient must have at least one site of measurable disease as per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria - Patient must have had no more than 3 lines of systemic therapy (including endocrine therapy) for metastatic disease to be eligible for phase IB and the last 10 patients of Cohort C; there is no limitation on the numbers of prior systemic therapies for phase IA and the first 2 patients of Cohort C - Patients who are currently taking fulvestrant without disease progression are eligible - Patient must have a life expectancy of >= 12 weeks - Patient must have adequate oran function as defined as: - Absolute neutrophil count (ANC) >= 1500/uL - Platelet count >= 100,000/uL - Hemoglobin >= 9 g/dL - Serum creatinine =< 1.5 x upper limit of normal (ULN) - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range (or =< 3.0 x ULN if liver metastases are present) - Serum bilirubin =< ULN (or =< 1.5 x ULN if liver metastases are present; or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert Syndrome) - Serum amylase =< ULN - Serum lipase =< ULN - Magnesium >= the lower limit of normal - Potassium within normal limits for the institution - Patient must have international normalized ratio (INR) =< 2 - Patient must have fasting plasma glucose =< 120 mg/dL (6.7 mmol/L) - Patient must have total calcium (corrected for serum albumin) within normal limits (bisphosphonate use for malignant hypercalcemia control is not allowed) - Patient must be able and willing to sign the consent form Exclusion Criteria: - Patient must not have received prior treatment with a P13K inhibitor - Patient must not have a known hypersensitivity to BKM120 or to its excipients - Patient must not have untreated brain metastases; however, patients with metastatic central nervous system (CNS) tumors may participate in this trial if the patient is: - 4 weeks from therapy completion (including radiation and/or surgery) - Clinically stable at the time of study entry - Not receiving corticosteroid therapy - Patient must not have acute or chronic liver disease, renal disease, or pancreatitis - Patient must not have any of the following mood disorders as judged by the Investigator or a Psychiatrist - Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others) - Greater than or equal to Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety - Patient must not meet the cut-off score of >= 10 in the Patient Health Questionnaire (PHQ-9) or a cut-off of >= 15 in the Generalized Anxiety Disorder (GAD)-7 mood scale, respectively, or select a positive response of 1, 2, or 3 to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9) - Patient must not have >= grade 2 diarrhea - Patient must not have active cardiac disease including any of the following: - Left ventricular ejection fraction (LVEF) < 50% as determined by Multiple Grated acquisition (MUGA) scan or echocardiogram (ECHO) - QTc > 480 msec on screening electrocardiogram (ECG) (using the QTcF formula) - Angina pectoris that requires the use of anti-anginal medication - Ventricular arrhythmias except for benign premature ventricular contractions - Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication - Conduction abnormality requiring a pacemaker - Valvular disease with document compromise in cardiac function - Symptomatic pericarditis - Patient must not have a history of cardiac dysfunction including any of the following: - Myocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function - History of documented congestive heart failure (New York Heart Association functional classification III-IV) - Documented cardiomyopathy - Patient must not have poorly controlled diabetes mellitus or steroid-induced diabetes mellitus (defined by fasting glucose >120 mg/dL or hemoglobin [Hb] A1c > 7%) - Patient must not have any other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol - Patient must not have significant symptomatic deterioration of lung function; if clinically indicated, pulmonary function tests including measures of predicted lung volumes; diffusion capacity of carbon monoxide (DLco), oxygen (O2) saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates - Patient must not have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection); patients with unresolved diarrhea will be excluded as previously indicated - Patient must not have been treated with any hematopoietic colony-stimulating growth factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF]) =< 2 weeks prior to starting study drug; erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment, may be continued - Patient must not have taken herbal medications and certain fruits within 7 days prior to starting study drug; herbal medications include, but are not limited to: St. Johns wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng; fruits include the CYP3A inhibitors Seville oranges, grapefruit, pummelos, or exotic citrus fruits - Patient must not be currently receiving treatment with medication with a known risk to prolong the QT interval or inducing Torsades de Pointes unless the treatment can either be discontinued or switched to a different medication prior to starting study drug; please refer to Table 5-2 for a list of prohibited QT prolonging drugs with risk of Torsades de Pointes - Patient must not be receiving chronic treatment with steroids or another immunosuppressive agent; Note: topical applications (e.g. --- P13K ---

14 Phase I/II Study of the Combination of BKM120 and Bevacizumab in Patients With Refractory Solid Tumors (Phase I) and Relapsed/Refractory Glioblastoma Multiforme (Phase II)

In this phase I/II study,investigators are evaluating the feasibility and efficacy of the combination of BKM120, an oral inhibitor of PI3 kinase, and bevacizumab in the treatment of patients with relapsed/refractory GBM. In the Phase I part of the trial, the optimal BKM120 dose to be administered with a standard dose of bevacizumab will be determined in patients with refractory solid tumors. Although it is unlikely that the concurrent administration of bevacizumab will alter the pharmacokinetics of BKM120, limited pharmacokinetic sampling will be performed on all patients treated during the Phase II portion of the study. Assuming this combination is feasible, the Phase II portion of the study will proceed, using the doses determined in the Phase I portion. In the phase II portion, eligible patients will be limited to those with recurrent/progressive GBM following 1st line combined modality therapy.

NCT01349660 Glioblastoma Multiforme Drug: Bevacizumab Drug: BKM120

MeSH:Glioblastoma

HPO:Glioblastoma multiforme

- Patients who have received prior treatment with a P13K inhibitor. --- P13K ---

15 A Phase 1a/1b, Multicenter, Open Label, Dosefinding Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the Dual Dna-pk and Tor Kinase Inhibitor, Cc-115, Administered Orally to Subjects With Advanced Solid Tumors and Hematologic Malignancies

The main purpose of this first human study with CC-115 is to assess the safety and action of a new class of experimental drug (dual DNA-PK and TOR kinase inhibitors) in patients with advanced tumors unresponsive to standard therapies and to determine the appropriate dose and tumor types for later-stage clinical trials. The bioavailability of tablet and capsule formulations under fasting and fed conditions will also be evaluated in some patients.

NCT01353625 Glioblastoma Multiforme Squamous Cell Carcinoma of Head and Neck Prostate Cancer Ewing's Osteosarcoma Chronic Lymphocytic Leukemia Neoplasm Metastasis Drug: CC-115

MeSH:Prostatic Neoplasms Neoplasm Metastasis Glioblastoma Leukemia, Lymphocytic, Chronic, B-Cell Hematologic Neoplasms Osteosarcoma Squamous Cell Carcinoma of Head and Neck Neoplasms

HPO:Chronic lymphatic leukemia Glioblastoma multiforme Hematological neoplasm Leukemia Neoplasm Osteosarcoma Prostate cancer Prostate neoplasm

Prior treatment with some drugs targeting mTOR, P13K and related pathways is now permitted. --- P13K ---

16 A Phase II Study of Sunitinib or Temsirolimus in Patients With Advanced Rare Tumours

This research is being done because there is no treatment that will cure this type of cancer. Although some types of chemotherapy can cause this cancer to shrink for a time, better options are needed.

NCT01396408 Advanced Rare Tumours Drug: Sunitinib Drug: Temsirolimus

Adverse events will be monitored on an ongoing basis by the central office and their frequencies reported annually at investigators' meetings.. Eligibility Criteria - ALL Patients Patients must have histologically or cytologically confirmed diagnosis of a rare tumour as follows: 1. Vascular sarcomas: Angiosarcoma, hemangiosarcoma, hemangiopericytoma, hemangioblastomas; 2. Clear cell carcinomas of the ovary, endometrium; 3. Medullary thyroid carcinoma; 4. Neuroendocrine tumours: paragangliomas and pheochromocytomas only; 5. Adrenocorticocarcinoma; 6. Thymic carcinoma; 7. Fibrolamellar hepatocellular carcinoma; 8. Exploratory genetic cohort for sunitinib: Rare tumours with somatic or germline mutations in sunitinib targets such as VEGFR, PDGFR, KIT, RET; 9. Exploratory genetic cohort for temsirolimus: Rare tumours arising from known or suspected germline mutations in mTOR pathway such as PTEN, TS1/2, LKB1, NF1/2 or somatic mutations in the mTOR pathway such as mutation or amplification of P13K or AKT; 10. --- P13K ---

rifampin phenytoin rifabutin St. John's wort carbamazepine efavirenz phenobarbital tipranavir Eligibility Criteria - ALL Patients Patients must have histologically or cytologically confirmed diagnosis of a rare tumour as follows: 1. Vascular sarcomas: Angiosarcoma, hemangiosarcoma, hemangiopericytoma, hemangioblastomas; 2. Clear cell carcinomas of the ovary, endometrium; 3. Medullary thyroid carcinoma; 4. Neuroendocrine tumours: paragangliomas and pheochromocytomas only; 5. Adrenocorticocarcinoma; 6. Thymic carcinoma; 7. Fibrolamellar hepatocellular carcinoma; 8. Exploratory genetic cohort for sunitinib: Rare tumours with somatic or germline mutations in sunitinib targets such as VEGFR, PDGFR, KIT, RET; 9. Exploratory genetic cohort for temsirolimus: Rare tumours arising from known or suspected germline mutations in mTOR pathway such as PTEN, TS1/2, LKB1, NF1/2 or somatic mutations in the mTOR pathway such as mutation or amplification of P13K or AKT; 10. --- P13K ---

17 A Phase 1b/2 Study of BEZ235 in Patients With Advanced Renal Cell Carcinoma (RCC)

This study tests a new medication for treatment of kidney cancer, called BEZ235. This medication works by blocking several mechanisms that the cancer needs to grow and survive. By blocking these mechanisms, the medication can thus suppress further growth of the cancer, possibly kill cancer cells. Older kidney cancer medications (such as temsirolimus [Torisel®] or everolimus [Afinitor®]) typically only block one mechanism in cancer cells, so the investigators think that BEZ235 may work even better against kidney cancer. The purpose of the first part of this study is to test the safety of giving BEZ235 at different doses. The investigators are trying to find a safe dose of BEZ235 and want to find out what effects, good and/or bad, it has on the patient and the cancer.

NCT01453595 Renal Cancer Drug: BEZ235

MeSH:Carcinoma Carcinoma, Renal Cell Kidney Neoplasms

HPO:Carcinoma Clear cell renal cell carcinoma Papillary renal cell carcinoma Renal cell carcinoma Renal neoplasm

Exclusion Criteria: - Patients who have received prior treatment with a P13K inhibitor (Phase 2 portion only). --- P13K ---

18 A Phase I Study of BKM120 and Everolimus in Advanced Solid Malignancies

This study will assess the safety of combining two agents (everolimus and BKM120) for the treatment of advanced cancer arising from solid organ in patients who are no longer benefiting from or unable to withstand standard treatment of these conditions.

NCT01470209 Solid Tumors Lung Cancer Drug: BKM120 Drug: Everolimus

MeSH:Lung Neoplasms

HPO:Neoplasm of the lung

Ability and willingness to undergo repeat tumor biopsies (the biopsy is optional and only applicable to subjects considered for the expansion cohort stage of the study) Exclusion Criteria: 1. Patients who have received prior treatment with a phosphatidylinositol 3-kinase (P13K) inhibitor or RAD001 (if discontinued for toxicity) 2. Patients with a known hypersensitivity to BKM120, RAD001 (including other rapalogs) or their excipients 3. Patients with untreated symptomatic brain metastases are excluded. --- P13K ---

19 A Phase I Study of the HER1, HER2 Dual Kinase Inhibitor, Lapatinib Plus the Proteosomal Inhibitor Bortezomib in Patients With Advanced Malignancies

This study is for patients with an advanced type of cancer for which no curative treatment exists. The purpose of this study is to test the safety and efficacy of the combination of the study drugs, lapatinib and bortezomib. Lapatinib is a drug that targets two proteins important for the growth of cancer cells known as HER1 (EGFR) and HER2. By inhibiting these proteins, lapatinib can inhibit cancer cell growth and even lead to their death. Lapatinib is an oral pill given by mouth once every day. Lapatinib is approved by the FDA for patients with breast cancer. Bortezomib is a drug that targets a part of cancer cells known as the proteosome. By inhibiting the proteosome, bortezomib can inhibit cancer cell growth and even lead to their death. Bortezomib is given intravenously, once a week, 2 out of every 3 weeks. Bortezomib is approved by the FDA for patients with multiple myeloma and mantle cell lymphoma. This research is being done because it is not known if the combination of lapatinib and bortezomib will work better than lapatinib or bortezomib alone, although in the lab and in animal studies the combination of the two drugs was much more effective than either drug alone. As part of this study biopsies will be taken of patients' tumors before any treatment, after starting lapatinib alone, and after receiving both lapatinib and bortezomib. Investigators want to study what markers inside tumors may relate to how well these two medications work. These biopsies are required as part of the study.

NCT01497626 Advanced Solid Tumors Drug: Lapatinib and bortezomib

MeSH:Neoplasms

HPO:Neoplasm

To assess changes in the following in serial tumor samples: EGFR, HER2, HER3, AKT, Actin, ERK, GSK3a-beta, IGF-1R, MEK 1/2, mTOR, p70S6, P13K, PTEN, SHC Y317, NFKB, IKB, CFK4, CDK2, cyclin D1, cyclin A, Cyclin E, p15, p16, p21, p27, beta-catenin, and ras gene mutation. --- P13K ---

20 An Open Label, Phase II Trial of BKM120 in Cancers With PIK3CA Activating Mutations

In people whos cancers have a PIK3CA mutation, this trial will be evaluating the drug BKM120 as a possible treatment. BKM120 works by blocking the phosphatidylinositol-3-kinase (PI3K)pathway, thereby inhibiting tumor growth and survival. The purpose of this study is to learn if the study drug BKM120 can shrink or slow the growth of your tumor. The safety of BKM120 will also be studied. Your physical state, symptoms, change in the size of your tumor, and laboratory findings obtained while you are on study will help the research team decide if BKM120 is safe and effective in patients with advanced cancers.

NCT01501604 Lung Cancer Breast Cancer Colorectal Cancer Cholangiocarcinoma Solid Tumors Drug: BKM120

MeSH:Cholangiocarcinoma

HPO:Cholangiocarcinoma

The PIK3CA mutation must be documented in a CLIA approved laboratory Exclusion Criteria: - Prior treatment with a P13K inhibitor - Known hypersensitivity to BKM120 or its excipients - Untreated brain metastases - Acute or chronic liver, renal disease or pancreatitis - Currently treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A - Diarrhea >/= CTCAE grade 2 - Any concurrent severe and/or uncontrolled medical condition - Active cardiac disease - History of cardiac dysfunction - Poorly controlled diabetes mellitus or steroid-induced diabetes mellitus - Significant symptomatic deterioration of lung function - Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKDM120 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) - Currently taking therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulant - Pregnant or breast-feeding - Known diagnosis of HIV infection - History of another malignancy within 3 years, except cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix - Unable to swallow the medication in its prescribed form Inclusion Criteria: - At least 1 site of measurable disease - Life expectancy >/= 12 weeks - Adequate marrow and organ function - Diagnosis of lung cancer, breast cancer, colorectal cancer, cholangiocarcinoma, gastric cancer, pancreatic cancer, prostate cancer, uterine cancer, ovarian cancer, esophageal cancer, or head and neck cancer - Pathologically documented, definitively diagnosed, advanced solid tuor that is refractory to standard treatment, for which no standard therapy is available, or the subject refuses standard therapy - Cancer must have at least one of the following PIK3CA mutations: E542K, E545K, H1047R, H1047L. --- P13K ---

The PIK3CA mutation must be documented in a CLIA approved laboratory Exclusion Criteria: - Prior treatment with a P13K inhibitor - Known hypersensitivity to BKM120 or its excipients - Untreated brain metastases - Acute or chronic liver, renal disease or pancreatitis - Currently treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A - Diarrhea >/= CTCAE grade 2 - Any concurrent severe and/or uncontrolled medical condition - Active cardiac disease - History of cardiac dysfunction - Poorly controlled diabetes mellitus or steroid-induced diabetes mellitus - Significant symptomatic deterioration of lung function - Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKDM120 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) - Currently taking therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulant - Pregnant or breast-feeding - Known diagnosis of HIV infection - History of another malignancy within 3 years, except cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix - Unable to swallow the medication in its prescribed form Lung Cancer Breast Cancer Colorectal Cancer Cholangiocarcinoma Solid Tumors Cholangiocarcinoma Subjects enrolled in this study will receive BKM120 once daily, orally, in cycles of 28 days. --- P13K ---

21 Evaluation of PI3K/AKT/mTOR Signaling Pathway Using BKM120 in Early Breast Cancer

BKM120 is a potent and highly specific oral pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor, currently under investigation in a first-in-man study in patients with advanced solid tumors (wild type and PIK3CA-mutated). Consistent, dose-dependent pharmacodynamic activity has been demonstrated and clear signs of anti-tumor activity have been seen with BKM120.

NCT01513356 Breast Cancer Drug: BKM120

MeSH:Breast Neoplasms

HPO:Breast carcinoma Neoplasm of the breast

- Patients must meet the following laboratory criteria within 7 days prior to start the study treatment: - Hematology - Neutrophil count of > 1200/mm3 - Platelet count of > 100,000/ mm3 - Hemoglobin > 90g/L - Biochemistry - AST/SGOT and ALT/SGPT < 2.5 x upper limit of normal (ULN) or < 5.0 x ULN if the transaminase elevation is due to liver metastases - Total bilirubin < 1.5 x ULN [Patients with Gilbert Syndrome must have total bilirubin < 3 ULN] - Cholesterol < ULN - 7.75 mmol/L and Triglycerides < ULN - 2.5 x ULN (with lipid-lowering drugs permitted) - Serum creatinine < 1.5 x ULN or 24-hour creatinine clearance > 60 mL/min - Serum albumin > LLN or > 30 g/L - Fasting plasma glucose ≤ 140 mg/dL (7.8 mmol/L) Exclusion Criteria: - Patients who have received prior treatment with a P13K inhibitor - Patients with a known hypersensitivity to BKM120 or to its excipients - Patients with a history of photosensitivity reactions to other drugs - Patients with the following mood disorders as judged by the Investigator or a psychiatrist, or as result of patient's mood assessment questionnaire: - Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others) - ≥ CTCAE grade 3 anxiety The psychiatric judgment overrules the mood assessment questionnaire result/investigators judgment. --- P13K ---

22 A Phase I Study of the PI3-Kinase Inhibitor BKM120 in Combination With Docetaxel in Patients With Advanced Solid Tumors.

This phase I trial studies the side effects and best dose of PI3K inhibitor BKM120 when given together with docetaxel in treating patients with advanced solid tumor that is locally advanced, cannot be removed by surgery, or metastatic. PI3K inhibitor BKM120 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving PI3K inhibitor BKM120 together with docetaxel may kill more tumor cells.

NCT01540253 Uns Unspecified Adult Solid Tumor, Protocol Specific Drug: PI3K inhibitor BKM120 Drug: docetaxel Other: pharmacological study Other: questionnaire administration Other: laboratory biomarker analysis

MeSH:Neoplasms

HPO:Neoplasm

dexamethasone 2 mg/day, prednisolone 10 mg/day) for at least 14 days before start of study treatment are eligible - Patients who are currently treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug (please note that co-treatment with weak inhibitors of CYP3A is allowed) - Patients who have received chemotherapy or targeted anticancer therapy =< 4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug must recover to a grade 1 before starting the trial - Patients who have received any continuous or intermittent small molecule therapeutics (excluding monoclonal antibodies) =< 5 effective half-lives prior to starting study drug or who have not recovered from side effects of such therapy - No concurrent intake of valproic acid, rifampin, phenobarbital, phenytoin, or carbamazepine - Patients who are currently taking therapeutic doses of warfarin sodium or any other Coumadin derivative anticoagulant - Patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator Uns Unspecified Adult Solid Tumor, Protocol Specific Neoplasms PRIMARY OBJECTIVES: I. To determine the dose-limiting toxicities and identify the recommended phase II dose of the combination of docetaxel and BKM 120 (P13K inhibitor BKM120) in patients with advanced solid tumors. --- P13K ---

23 A Study of BKM120 as a Single Agent in First Line Therapy in Advanced, Metastatic, or Recurrent Endometrial Cancers

This is a phase II open label fixed dose study in subjects with advanced, metastatic, or refractory endometrial or ovarian, fallopian tube, or primary peritoneal cancer with PI3 kinase pathway activation as demonstrated by PIK3CA gene mutation, PTEN gene mutation, or PTEN null/low protein expression.

NCT01550380 Endometrial Cancer Drug: BKM120

MeSH:Endometrial Neoplasms

HPO:Endometrial carcinoma

Exclusion Criteria: - Patients who have received prior treatment with a P13K inhibitor. --- P13K ---

24 Phase II Study of Buparlisib in Metastatic Transitional Cell Carcinoma of the Urothelium

The purpose of this study is to learn what effects, good and/or bad, Buparlisib has on advanced urothelial cancer. Buparlisib is a pill that works by shutting down some of the signals in cancer cells that make tumors grow. It is being tested in patients in research studies such as this one. As of 2010, more than 80 patients with various types of cancer have received treatment with Buparlisib in research studies. This clinical research study is divided into two parts. The goal of the first part of this study is to learn if the study drug Buparlisib can shrink or slow the growth of cancer in patients with urothelial tumors. The goal of the second part of this study is to learn if the study drug Buparlisib can shrink or slow the growth of urothelial tumors in patients known to have certain genetic alterations that cause these types of tumors. The study doctor will inform the patient which part of the study is currently enrolling participants. Participants in both parts of the study will receive the same treatment and tests. The safety of this drug will also be studied in both parts. The physical state, changes in the size of the tumor, and laboratory findings taken while on-study will help us decide if Buparlisib is safe and effective.

NCT01551030 Metastatic Transitional Cell Carcinoma of the Urothelium Drug: Buparlisib

MeSH:Carcinoma Carcinoma, Transitional Cell

HPO:Carcinoma

- Life expectancy of ≥ 12 weeks - Adequate bone marrow function as shown by: ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, - Hemoglobin >9 g/dL - Total calcium (corrected for serum albumin) within normal limits (bisphosphonate use for malignant hypercalcemia control is not allowed) - Corrected Calcium = (0.8 * (Normal Albumin - Pt's Albumin)) + Serum Ca - Potassium and magnesium within normal limits - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range [or ≤ 3.0 x upper limit of normal (ULN) if liver metastases are present] - Serum bilirubin within normal range (or ≤ 1.5 x ULN if liver metastases are present; or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in patients with welldocumented Gilbert syndrome) - Serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50 mL/min - INR ≤ 2 - Serum amylase and lipase ≤ ULN - Fasting plasma glucose ≤ 120 mg/dL (6.7 mmol/L) - Ability to swallow oral medication Exclusion Criteria: - Patients who have received prior treatment with a P13K inhibitor. --- P13K ---

25 A Phase 1b Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of GS-9820 in Subjects With Lymphoid Malignancies

This study is to determine the appropriate dosing regimen of GS-9820 in subjects with lymphoid malignancies. This is a Phase 1b, open-label, dose-escalation and expansion study evaluating the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of GS-9820.

NCT01705847 Lymphoid Malignancies Drug: GS-9820

MeSH:Neoplasms

HPO:Neoplasm

Pharmacodynamics to measure changes in the phosphatidylinositol 3-kinase (P13K) delta pathway activation and changes in plasma concentration of disease-associated chemokines and cytokines. --- P13K ---

26 A Pilot Study of the PI3K Inhibitor BKM120 in Patients With Relapsed Lymphoma

This pilot clinical trial studies how well buparlisib works in treating patients with non-Hodgkin lymphoma that has returned after a period of improvement or has not responded to previous treatment. Buparlisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

NCT01719250 Recurrent Adult Diffuse Large Cell Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Refractory Mantle Cell Lymphoma Transformed Recurrent Non-Hodgkin Lymphoma Drug: Buparlisib Other: Laboratory Biomarker Analysis Other: Questionnaire Administration

MeSH:Lymphoma Lymphoma, Non-Hodgkin Lymphoma, Mantle-Cell Lymphoma, Large B-Cell, Diffuse

HPO:Lymphoma Non-Hodgkin lymphoma

Will be estimated using the method of Kaplan-Meier.. Inclusion Criteria: - Biopsy-proven relapsed, refractory or residual aggressive B-cell non-Hodgkin lymphoma; NOTE: re-biopsy is necessary unless the patient has had a previous biopsy < 168 days prior to registration on this protocol and there has been no intervening treatment; eligible tumor types are diffuse large B-cell non-Hodgkin lymphoma (NHL), mantle cell lymphoma, transformed NHL, and follicular grade III - Not a candidate or has declined standard salvage therapy for their disease - Measurable disease as defined by at least ONE of the following: - Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) or the CT portion of the positron emission tomography (PET)/CT: must have at least one lesion that has a single diameter of >= 2 cm or tumor cells in the blood >= 5 x 10^9/L - Skin lesions can be used if the area is >= 2 cm in at least one diameter and photographed with a ruler - Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2 - Absolute neutrophil count (ANC) >= 1000/uL - Hemoglobin (Hgb) >= 9 g/dl - Platelets (PLT) >= 100,000/uL - Serum bilirubin within normal range (or =< 1.5 x upper limit of normal [ULN] if liver metastases are present; or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert syndrome) - Aspartate aminotransferase (AST) within normal limits or =< 3 x ULN if due to lymphoma - Serum creatinine =< 1.5 x ULN or 24-hour clearance >= 50 mL/min - Magnesium >= lower limit of normal (LLN) - Potassium >= LLN - Serum amylase =< ULN - Serum lipase =< ULN - Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L) - Serum calcium =< 10.9 mg/dL - Negative pregnancy test done =< 72 hours prior to starting drug, for women of childbearing potential only - Provide informed written consent - Willing to return to Mayo Clinic Rochester for follow-up - Willing to provide blood samples for correlative research purposes - Willingness to take BKM120 orally Exclusion Criteria: - Any of the following: - Pregnant women - Nursing women - Women of childbearing potential who are unwilling to employ highly effective contraception during dosing with BKM120 and for 4 weeks after the final dose of treatment; NOTE: women of childbearing potential are defined as all women physiologically capable of becoming pregnant - Men of childbearing potential who are unwilling to employ highly effective contraception during dosing with BKM120 and for 16 weeks after the final dose of treatment and should not a father a child during this time; NOTE: men of childbearing potential are defined as all males physiologically capable of conceiving offspring - NOTE: the highly effective contraception is defined as either: - True abstinence: when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception - Sterilization: have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment - Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate); for female subjects on the study, the vasectomized male partner should be the sole partner for that patient - Use of a combination of any two of the following (a+b): 1. Placement of an intrauterine device (IUD) or intrauterine system (IUS) 2. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository - Oral contraception, injected or implanted hormonal methods are not allowed - Uncontrolled infection - Average baseline of >= 4 stools per day - Therapy with myelosuppressive chemotherapy or biologic therapy < 21 days prior to registration unless the patient has recovered from the nadir of the previous treatment to a level that meets the inclusion eligibility criteria of this protocol - Patients who have received any continuous or intermittent small molecule therapeutics (excluding monoclonal antibodies) =< 5 effective half-lives prior to registration or who have not recovered from side effects of such therapy - Received wide field radiotherapy =< 28 days or limited field radiation for palliation =< 14 days prior to registration or who have not recovered from side effects of such therapy - Receiving corticosteroids > 10 mg of prednisone per day (or equivalent); NOTE: patients may be receiving stable doses of corticosteroids with a maximum dose of 10 mg of prednisone per day if they are being given for disorders other than lymphoma such as rheumatoid arthritis, polymyalgia rheumatica or adrenal insufficiency, or asthma - Persistent toxicities >= grade 2 from prior chemotherapy or biological therapy regardless of interval since last treatment - Active cardiac disease including any of the following: - Left ventricular ejection fraction (LVEF) < 45% as determined by multi gated acquisition (MUGA) scan or echocardiogram (ECHO) - Fridericia's corrected QT interval (QTcF) > 450 msec on screening electrocardiogram (ECG) (using the QTcF formula) - Unstable angina pectoris; patients with unstable angina should have angina controlled before entering the study - Ventricular arrhythmias except for benign premature ventricular contractions - Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication - Conduction abnormality requiring a pacemaker - Symptomatic pericarditis - Myocardial infraction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function - History of documented congestive heart failure (New York Heart Association functional classification III-IV) - Documented cardiomyopathy - Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation) - Known positivity for human immunodeficiency virus (HIV); note: baseline testing for HIV is not required - Active hepatitis B or C with uncontrolled disease; note: a detailed assessment of hepatitis B/C medical history and risk factors must be done at screening for all patients; hepatitis B surface antigen (HBsAg) and hepatitis C virus (HCV) ribonucleic acid (RNA) polymerase chain reaction (PCR) testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior hepatitis B virus (HBV) infection - Other active malignancy requiring treatment that would interfere with the assessments of response of the lymphoma to protocol treatment - Inability to swallow or impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of the drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection) that would preclude use of oral medications - Any severe and/or uncontrolled medical conditions such as diabetes, poor lung function, or other conditions that, in the treating physician's opinion, could adversely impact their ability to participate in the study - Patients who have received prior treatment with a P13K inhibitor; patients with prior mammalian target of rapamycin (mTOR) inhibitor therapy are eligible - Using medications that have a strong risk of prolonging the QT interval or inducing torsades de pointes - Major surgery =< 14 days prior to registration or have not recovered from side effects of such therapy - Currently being treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5), (please note that co-treatment with weak inhibitors of cytochrome P450, family 3, subfamily A [CYP3A] is allowed) - Receiving certain fruits or herbal preparations/medications including, but are not limited to: St. John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, ginseng; fruits include the CYP3A inhibitors Seville oranges, grapefruit, pummelos, or exotic citrus fruits; NOTE: patients should stop using these fruits and herbal medications 7 days prior to first dose of study drug - Primary central nervous system (CNS) lymphoma or active metastases to the CNS; NOTE: active is defined as requiring therapy such as surgery, radiation, or chemotherapy =< 28 days of study registration or ongoing corticosteroid therapy for CNS disease - The following mood disorders as judged by the Investigator or a psychiatrist, or as a result of patient's mood assessment questionnaire: - Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others) - >= Common Terminology Criteria of Adverse Events (CTCAE) grade 3 anxiety - Meets the cut-off score of >= 12 in the Patient Health Questionnaire (PHQ)-9 or a cut-off of >= 15 in the Generalized Anxiety Disorder (GAD)-7 mood scale, respectively, or selects a positive response of "1, 2, or 3" to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9) - Treated with any hematopoietic colony-stimulating growth factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF]) =< 2 weeks prior to study registration; NOTE: erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to study registration, may be continued Inclusion Criteria: - Biopsy-proven relapsed, refractory or residual aggressive B-cell non-Hodgkin lymphoma; NOTE: re-biopsy is necessary unless the patient has had a previous biopsy < 168 days prior to registration on this protocol and there has been no intervening treatment; eligible tumor types are diffuse large B-cell non-Hodgkin lymphoma (NHL), mantle cell lymphoma, transformed NHL, and follicular grade III - Not a candidate or has declined standard salvage therapy for their disease - Measurable disease as defined by at least ONE of the following: - Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) or the CT portion of the positron emission tomography (PET)/CT: must have at least one lesion that has a single diameter of >= 2 cm or tumor cells in the blood >= 5 x 10^9/L - Skin lesions can be used if the area is >= 2 cm in at least one diameter and photographed with a ruler - Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2 - Absolute neutrophil count (ANC) >= 1000/uL - Hemoglobin (Hgb) >= 9 g/dl - Platelets (PLT) >= 100,000/uL - Serum bilirubin within normal range (or =< 1.5 x upper limit of normal [ULN] if liver metastases are present; or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert syndrome) - Aspartate aminotransferase (AST) within normal limits or =< 3 x ULN if due to lymphoma - Serum creatinine =< 1.5 x ULN or 24-hour clearance >= 50 mL/min - Magnesium >= lower limit of normal (LLN) - Potassium >= LLN - Serum amylase =< ULN - Serum lipase =< ULN - Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L) - Serum calcium =< 10.9 mg/dL - Negative pregnancy test done =< 72 hours prior to starting drug, for women of childbearing potential only - Provide informed written consent - Willing to return to Mayo Clinic Rochester for follow-up - Willing to provide blood samples for correlative research purposes - Willingness to take BKM120 orally Exclusion Criteria: - Any of the following: - Pregnant women - Nursing women - Women of childbearing potential who are unwilling to employ highly effective contraception during dosing with BKM120 and for 4 weeks after the final dose of treatment; NOTE: women of childbearing potential are defined as all women physiologically capable of becoming pregnant - Men of childbearing potential who are unwilling to employ highly effective contraception during dosing with BKM120 and for 16 weeks after the final dose of treatment and should not a father a child during this time; NOTE: men of childbearing potential are defined as all males physiologically capable of conceiving offspring - NOTE: the highly effective contraception is defined as either: - True abstinence: when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception - Sterilization: have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment - Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate); for female subjects on the study, the vasectomized male partner should be the sole partner for that patient - Use of a combination of any two of the following (a+b): 1. Placement of an intrauterine device (IUD) or intrauterine system (IUS) 2. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository - Oral contraception, injected or implanted hormonal methods are not allowed - Uncontrolled infection - Average baseline of >= 4 stools per day - Therapy with myelosuppressive chemotherapy or biologic therapy < 21 days prior to registration unless the patient has recovered from the nadir of the previous treatment to a level that meets the inclusion eligibility criteria of this protocol - Patients who have received any continuous or intermittent small molecule therapeutics (excluding monoclonal antibodies) =< 5 effective half-lives prior to registration or who have not recovered from side effects of such therapy - Received wide field radiotherapy =< 28 days or limited field radiation for palliation =< 14 days prior to registration or who have not recovered from side effects of such therapy - Receiving corticosteroids > 10 mg of prednisone per day (or equivalent); NOTE: patients may be receiving stable doses of corticosteroids with a maximum dose of 10 mg of prednisone per day if they are being given for disorders other than lymphoma such as rheumatoid arthritis, polymyalgia rheumatica or adrenal insufficiency, or asthma - Persistent toxicities >= grade 2 from prior chemotherapy or biological therapy regardless of interval since last treatment - Active cardiac disease including any of the following: - Left ventricular ejection fraction (LVEF) < 45% as determined by multi gated acquisition (MUGA) scan or echocardiogram (ECHO) - Fridericia's corrected QT interval (QTcF) > 450 msec on screening electrocardiogram (ECG) (using the QTcF formula) - Unstable angina pectoris; patients with unstable angina should have angina controlled before entering the study - Ventricular arrhythmias except for benign premature ventricular contractions - Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication - Conduction abnormality requiring a pacemaker - Symptomatic pericarditis - Myocardial infraction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function - History of documented congestive heart failure (New York Heart Association functional classification III-IV) - Documented cardiomyopathy - Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation) - Known positivity for human immunodeficiency virus (HIV); note: baseline testing for HIV is not required - Active hepatitis B or C with uncontrolled disease; note: a detailed assessment of hepatitis B/C medical history and risk factors must be done at screening for all patients; hepatitis B surface antigen (HBsAg) and hepatitis C virus (HCV) ribonucleic acid (RNA) polymerase chain reaction (PCR) testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior hepatitis B virus (HBV) infection - Other active malignancy requiring treatment that would interfere with the assessments of response of the lymphoma to protocol treatment - Inability to swallow or impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of the drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection) that would preclude use of oral medications - Any severe and/or uncontrolled medical conditions such as diabetes, poor lung function, or other conditions that, in the treating physician's opinion, could adversely impact their ability to participate in the study - Patients who have received prior treatment with a P13K inhibitor; patients with prior mammalian target of rapamycin (mTOR) inhibitor therapy are eligible - Using medications that have a strong risk of prolonging the QT interval or inducing torsades de pointes - Major surgery =< 14 days prior to registration or have not recovered from side effects of such therapy - Currently being treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5), (please note that co-treatment with weak inhibitors of cytochrome P450, family 3, subfamily A [CYP3A] is allowed) - Receiving certain fruits or herbal preparations/medications including, but are not limited to: St. John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, ginseng; fruits include the CYP3A inhibitors Seville oranges, grapefruit, pummelos, or exotic citrus fruits; NOTE: patients should stop using these fruits and herbal medications 7 days prior to first dose of study drug - Primary central nervous system (CNS) lymphoma or active metastases to the CNS; NOTE: active is defined as requiring therapy such as surgery, radiation, or chemotherapy =< 28 days of study registration or ongoing corticosteroid therapy for CNS disease - The following mood disorders as judged by the Investigator or a psychiatrist, or as a result of patient's mood assessment questionnaire: - Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others) - >= Common Terminology Criteria of Adverse Events (CTCAE) grade 3 anxiety - Meets the cut-off score of >= 12 in the Patient Health Questionnaire (PHQ)-9 or a cut-off of >= 15 in the Generalized Anxiety Disorder (GAD)-7 mood scale, respectively, or selects a positive response of "1, 2, or 3" to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9) - Treated with any hematopoietic colony-stimulating growth factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF]) =< 2 weeks prior to study registration; NOTE: erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to study registration, may be continued Recurrent Adult Diffuse Large Cell Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Refractory Mantle Cell Lymphoma Transformed Recurrent Non-Hodgkin Lymphoma Lymphoma Lymphoma, Non-Hodgkin Lymphoma, Mantle-Cell Lymphoma, Large B-Cell, Diffuse PRIMARY OBJECTIVES: I. To evaluate the clinical benefit rate (complete response [CR], partial response [PR] or standard disease [SD] >= 6 months) with BKM120 (buparlisib) in patients with relapsed or refractory lymphoma. --- P13K ---

Will be estimated using the method of Kaplan-Meier.. Inclusion Criteria: - Biopsy-proven relapsed, refractory or residual aggressive B-cell non-Hodgkin lymphoma; NOTE: re-biopsy is necessary unless the patient has had a previous biopsy < 168 days prior to registration on this protocol and there has been no intervening treatment; eligible tumor types are diffuse large B-cell non-Hodgkin lymphoma (NHL), mantle cell lymphoma, transformed NHL, and follicular grade III - Not a candidate or has declined standard salvage therapy for their disease - Measurable disease as defined by at least ONE of the following: - Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) or the CT portion of the positron emission tomography (PET)/CT: must have at least one lesion that has a single diameter of >= 2 cm or tumor cells in the blood >= 5 x 10^9/L - Skin lesions can be used if the area is >= 2 cm in at least one diameter and photographed with a ruler - Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2 - Absolute neutrophil count (ANC) >= 1000/uL - Hemoglobin (Hgb) >= 9 g/dl - Platelets (PLT) >= 100,000/uL - Serum bilirubin within normal range (or =< 1.5 x upper limit of normal [ULN] if liver metastases are present; or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert syndrome) - Aspartate aminotransferase (AST) within normal limits or =< 3 x ULN if due to lymphoma - Serum creatinine =< 1.5 x ULN or 24-hour clearance >= 50 mL/min - Magnesium >= lower limit of normal (LLN) - Potassium >= LLN - Serum amylase =< ULN - Serum lipase =< ULN - Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L) - Serum calcium =< 10.9 mg/dL - Negative pregnancy test done =< 72 hours prior to starting drug, for women of childbearing potential only - Provide informed written consent - Willing to return to Mayo Clinic Rochester for follow-up - Willing to provide blood samples for correlative research purposes - Willingness to take BKM120 orally Exclusion Criteria: - Any of the following: - Pregnant women - Nursing women - Women of childbearing potential who are unwilling to employ highly effective contraception during dosing with BKM120 and for 4 weeks after the final dose of treatment; NOTE: women of childbearing potential are defined as all women physiologically capable of becoming pregnant - Men of childbearing potential who are unwilling to employ highly effective contraception during dosing with BKM120 and for 16 weeks after the final dose of treatment and should not a father a child during this time; NOTE: men of childbearing potential are defined as all males physiologically capable of conceiving offspring - NOTE: the highly effective contraception is defined as either: - True abstinence: when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception - Sterilization: have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment - Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate); for female subjects on the study, the vasectomized male partner should be the sole partner for that patient - Use of a combination of any two of the following (a+b): 1. Placement of an intrauterine device (IUD) or intrauterine system (IUS) 2. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository - Oral contraception, injected or implanted hormonal methods are not allowed - Uncontrolled infection - Average baseline of >= 4 stools per day - Therapy with myelosuppressive chemotherapy or biologic therapy < 21 days prior to registration unless the patient has recovered from the nadir of the previous treatment to a level that meets the inclusion eligibility criteria of this protocol - Patients who have received any continuous or intermittent small molecule therapeutics (excluding monoclonal antibodies) =< 5 effective half-lives prior to registration or who have not recovered from side effects of such therapy - Received wide field radiotherapy =< 28 days or limited field radiation for palliation =< 14 days prior to registration or who have not recovered from side effects of such therapy - Receiving corticosteroids > 10 mg of prednisone per day (or equivalent); NOTE: patients may be receiving stable doses of corticosteroids with a maximum dose of 10 mg of prednisone per day if they are being given for disorders other than lymphoma such as rheumatoid arthritis, polymyalgia rheumatica or adrenal insufficiency, or asthma - Persistent toxicities >= grade 2 from prior chemotherapy or biological therapy regardless of interval since last treatment - Active cardiac disease including any of the following: - Left ventricular ejection fraction (LVEF) < 45% as determined by multi gated acquisition (MUGA) scan or echocardiogram (ECHO) - Fridericia's corrected QT interval (QTcF) > 450 msec on screening electrocardiogram (ECG) (using the QTcF formula) - Unstable angina pectoris; patients with unstable angina should have angina controlled before entering the study - Ventricular arrhythmias except for benign premature ventricular contractions - Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication - Conduction abnormality requiring a pacemaker - Symptomatic pericarditis - Myocardial infraction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function - History of documented congestive heart failure (New York Heart Association functional classification III-IV) - Documented cardiomyopathy - Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation) - Known positivity for human immunodeficiency virus (HIV); note: baseline testing for HIV is not required - Active hepatitis B or C with uncontrolled disease; note: a detailed assessment of hepatitis B/C medical history and risk factors must be done at screening for all patients; hepatitis B surface antigen (HBsAg) and hepatitis C virus (HCV) ribonucleic acid (RNA) polymerase chain reaction (PCR) testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior hepatitis B virus (HBV) infection - Other active malignancy requiring treatment that would interfere with the assessments of response of the lymphoma to protocol treatment - Inability to swallow or impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of the drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection) that would preclude use of oral medications - Any severe and/or uncontrolled medical conditions such as diabetes, poor lung function, or other conditions that, in the treating physician's opinion, could adversely impact their ability to participate in the study - Patients who have received prior treatment with a P13K inhibitor; patients with prior mammalian target of rapamycin (mTOR) inhibitor therapy are eligible - Using medications that have a strong risk of prolonging the QT interval or inducing torsades de pointes - Major surgery =< 14 days prior to registration or have not recovered from side effects of such therapy - Currently being treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5), (please note that co-treatment with weak inhibitors of cytochrome P450, family 3, subfamily A [CYP3A] is allowed) - Receiving certain fruits or herbal preparations/medications including, but are not limited to: St. John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, ginseng; fruits include the CYP3A inhibitors Seville oranges, grapefruit, pummelos, or exotic citrus fruits; NOTE: patients should stop using these fruits and herbal medications 7 days prior to first dose of study drug - Primary central nervous system (CNS) lymphoma or active metastases to the CNS; NOTE: active is defined as requiring therapy such as surgery, radiation, or chemotherapy =< 28 days of study registration or ongoing corticosteroid therapy for CNS disease - The following mood disorders as judged by the Investigator or a psychiatrist, or as a result of patient's mood assessment questionnaire: - Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others) - >= Common Terminology Criteria of Adverse Events (CTCAE) grade 3 anxiety - Meets the cut-off score of >= 12 in the Patient Health Questionnaire (PHQ)-9 or a cut-off of >= 15 in the Generalized Anxiety Disorder (GAD)-7 mood scale, respectively, or selects a positive response of "1, 2, or 3" to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9) - Treated with any hematopoietic colony-stimulating growth factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF]) =< 2 weeks prior to study registration; NOTE: erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to study registration, may be continued Inclusion Criteria: - Biopsy-proven relapsed, refractory or residual aggressive B-cell non-Hodgkin lymphoma; NOTE: re-biopsy is necessary unless the patient has had a previous biopsy < 168 days prior to registration on this protocol and there has been no intervening treatment; eligible tumor types are diffuse large B-cell non-Hodgkin lymphoma (NHL), mantle cell lymphoma, transformed NHL, and follicular grade III - Not a candidate or has declined standard salvage therapy for their disease - Measurable disease as defined by at least ONE of the following: - Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) or the CT portion of the positron emission tomography (PET)/CT: must have at least one lesion that has a single diameter of >= 2 cm or tumor cells in the blood >= 5 x 10^9/L - Skin lesions can be used if the area is >= 2 cm in at least one diameter and photographed with a ruler - Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2 - Absolute neutrophil count (ANC) >= 1000/uL - Hemoglobin (Hgb) >= 9 g/dl - Platelets (PLT) >= 100,000/uL - Serum bilirubin within normal range (or =< 1.5 x upper limit of normal [ULN] if liver metastases are present; or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert syndrome) - Aspartate aminotransferase (AST) within normal limits or =< 3 x ULN if due to lymphoma - Serum creatinine =< 1.5 x ULN or 24-hour clearance >= 50 mL/min - Magnesium >= lower limit of normal (LLN) - Potassium >= LLN - Serum amylase =< ULN - Serum lipase =< ULN - Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L) - Serum calcium =< 10.9 mg/dL - Negative pregnancy test done =< 72 hours prior to starting drug, for women of childbearing potential only - Provide informed written consent - Willing to return to Mayo Clinic Rochester for follow-up - Willing to provide blood samples for correlative research purposes - Willingness to take BKM120 orally Exclusion Criteria: - Any of the following: - Pregnant women - Nursing women - Women of childbearing potential who are unwilling to employ highly effective contraception during dosing with BKM120 and for 4 weeks after the final dose of treatment; NOTE: women of childbearing potential are defined as all women physiologically capable of becoming pregnant - Men of childbearing potential who are unwilling to employ highly effective contraception during dosing with BKM120 and for 16 weeks after the final dose of treatment and should not a father a child during this time; NOTE: men of childbearing potential are defined as all males physiologically capable of conceiving offspring - NOTE: the highly effective contraception is defined as either: - True abstinence: when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception - Sterilization: have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment - Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate); for female subjects on the study, the vasectomized male partner should be the sole partner for that patient - Use of a combination of any two of the following (a+b): 1. Placement of an intrauterine device (IUD) or intrauterine system (IUS) 2. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository - Oral contraception, injected or implanted hormonal methods are not allowed - Uncontrolled infection - Average baseline of >= 4 stools per day - Therapy with myelosuppressive chemotherapy or biologic therapy < 21 days prior to registration unless the patient has recovered from the nadir of the previous treatment to a level that meets the inclusion eligibility criteria of this protocol - Patients who have received any continuous or intermittent small molecule therapeutics (excluding monoclonal antibodies) =< 5 effective half-lives prior to registration or who have not recovered from side effects of such therapy - Received wide field radiotherapy =< 28 days or limited field radiation for palliation =< 14 days prior to registration or who have not recovered from side effects of such therapy - Receiving corticosteroids > 10 mg of prednisone per day (or equivalent); NOTE: patients may be receiving stable doses of corticosteroids with a maximum dose of 10 mg of prednisone per day if they are being given for disorders other than lymphoma such as rheumatoid arthritis, polymyalgia rheumatica or adrenal insufficiency, or asthma - Persistent toxicities >= grade 2 from prior chemotherapy or biological therapy regardless of interval since last treatment - Active cardiac disease including any of the following: - Left ventricular ejection fraction (LVEF) < 45% as determined by multi gated acquisition (MUGA) scan or echocardiogram (ECHO) - Fridericia's corrected QT interval (QTcF) > 450 msec on screening electrocardiogram (ECG) (using the QTcF formula) - Unstable angina pectoris; patients with unstable angina should have angina controlled before entering the study - Ventricular arrhythmias except for benign premature ventricular contractions - Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication - Conduction abnormality requiring a pacemaker - Symptomatic pericarditis - Myocardial infraction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function - History of documented congestive heart failure (New York Heart Association functional classification III-IV) - Documented cardiomyopathy - Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation) - Known positivity for human immunodeficiency virus (HIV); note: baseline testing for HIV is not required - Active hepatitis B or C with uncontrolled disease; note: a detailed assessment of hepatitis B/C medical history and risk factors must be done at screening for all patients; hepatitis B surface antigen (HBsAg) and hepatitis C virus (HCV) ribonucleic acid (RNA) polymerase chain reaction (PCR) testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior hepatitis B virus (HBV) infection - Other active malignancy requiring treatment that would interfere with the assessments of response of the lymphoma to protocol treatment - Inability to swallow or impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of the drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection) that would preclude use of oral medications - Any severe and/or uncontrolled medical conditions such as diabetes, poor lung function, or other conditions that, in the treating physician's opinion, could adversely impact their ability to participate in the study - Patients who have received prior treatment with a P13K inhibitor; patients with prior mammalian target of rapamycin (mTOR) inhibitor therapy are eligible - Using medications that have a strong risk of prolonging the QT interval or inducing torsades de pointes - Major surgery =< 14 days prior to registration or have not recovered from side effects of such therapy - Currently being treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5), (please note that co-treatment with weak inhibitors of cytochrome P450, family 3, subfamily A [CYP3A] is allowed) - Receiving certain fruits or herbal preparations/medications including, but are not limited to: St. John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, ginseng; fruits include the CYP3A inhibitors Seville oranges, grapefruit, pummelos, or exotic citrus fruits; NOTE: patients should stop using these fruits and herbal medications 7 days prior to first dose of study drug - Primary central nervous system (CNS) lymphoma or active metastases to the CNS; NOTE: active is defined as requiring therapy such as surgery, radiation, or chemotherapy =< 28 days of study registration or ongoing corticosteroid therapy for CNS disease - The following mood disorders as judged by the Investigator or a psychiatrist, or as a result of patient's mood assessment questionnaire: - Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others) - >= Common Terminology Criteria of Adverse Events (CTCAE) grade 3 anxiety - Meets the cut-off score of >= 12 in the Patient Health Questionnaire (PHQ)-9 or a cut-off of >= 15 in the Generalized Anxiety Disorder (GAD)-7 mood scale, respectively, or selects a positive response of "1, 2, or 3" to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9) - Treated with any hematopoietic colony-stimulating growth factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF]) =< 2 weeks prior to study registration; NOTE: erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to study registration, may be continued Recurrent Adult Diffuse Large Cell Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Refractory Mantle Cell Lymphoma Transformed Recurrent Non-Hodgkin Lymphoma Lymphoma Lymphoma, Non-Hodgkin Lymphoma, Mantle-Cell Lymphoma, Large B-Cell, Diffuse PRIMARY OBJECTIVES: I. To evaluate the clinical benefit rate (complete response [CR], partial response [PR] or standard disease [SD] >= 6 months) with BKM120 (buparlisib) in patients with relapsed or refractory lymphoma. --- P13K --- --- P13K ---

27 Phase I Trial of BKM120 in Combination With Carboplatin and Pemetrexed in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

This phase I trial studies the side effects and best dose of PI3K inhibitor BKM120 when given together with carboplatin and pemetrexed disodium in treating patients with stage IV non-small cell lung cancer. PI3K inhibitor BKM120 and pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving PI3K inhibitor BKM120, carboplatin, and pemetrexed disodium together may kill more tumor cells

NCT01723800 Recurrent Non-small Cell Lung Cancer Stage IV Non-small Cell Lung Cancer Drug: PI3K inhibitor BKM120 Drug: pemetrexed disodium Drug: carboplatin Other: laboratory biomarker analysis Other: pharmacological study Procedure: quality-of-life assessment

MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung

HPO:Neoplasm of the lung Non-small cell lung carcinoma

Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated.. Inclusion Criteria: - Patients who have signed a written informed consent - Patients must have a histologic or cytologic diagnosis of advanced, nonsquamous NSCLC (stage IV by American Joint Committee on Cancer [AJCC] 7th edition [ed.]) - Patients should not have received prior systemic chemotherapy for metastatic disease (prior epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK], kinase inhibitor therapy is allowed); prior adjuvant or neoadjuvant therapy for early stage disease is allowed if received >= 12 months prior to study entry - Prior radiation therapy is allowed to < 25% of the bone marrow; prior radiation must be completed at least 2 weeks prior to day 1 of cycle 1, and patients must have recovered from the acute toxic effects - Eastern Cooperative Oncology Group (ECOG) performance status =< 2 - Patients must have at least one site of measurable disease (per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) - Absolute neutrophil count (ANC) >= 1.5 x 10^9/L - Platelets >= 100 x 10^9/L - Hemoglobin (Hb) > 9 g/dL - Total calcium (corrected for serum albumin) within normal limits (bisphosphonate use for malignant hypercalcemia control is not allowed) - Magnesium >= the lower limit of normal (LLN) - Potassium within normal limits for the institution - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range (or =< 3 x upper limit of normal [ULN] if liver metastases are present) - Serum bilirubin within normal range (or =< 1.5 x ULN if liver metastases are present) - Serum creatinine =< 1.5 x ULN or calculated or 24-hour clearance >= 45 mL/min (calculated creatinine clearance based on Cockcroft-Gault formula) - Serum phosphorus >= LLN - Serum amylase =< ULN - Serum lipase =< ULN - Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L) - Negative serum pregnancy test within 72 hours before starting study treatment in women with childbearing potential - International normalized ratio (INR) =< 2 Exclusion Criteria: - Patients who have received prior treatment with a P13K inhibitor or mammalian target of rapamycin (mTOR)-directed inhibitor - Patients with a known hypersensitivity of BKM120 or to its excipients - Patients with anaplastic lymphoma kinase (ALK) rearrangement or an activating epidermal growth factor receptor (EGFR) mutation who have not received and progressed on appropriate tyrosine kinase inhibitor therapy - Patients with untreated brain metastases are excluded; however, patients with metastatic central nervous system (CNS) tumors may participate in this trial, if the patient is > 2 weeks from therapy completion (incl. --- P13K ---

age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels > 40 mIU/mL (for United States [US] only: and estradiol < 20 pg/mL) or have had surgical bilateral oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential - Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during treatment for 5 T1/2 (8 days) after stopping treatment and for additional 12 weeks (3 months in total after study drug discontinuation); the highly effective contraception is defined as either: - True abstinence: when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception - Sterilization: have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment - Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate); for female subjects on the study, the vasectomized male should be the sole partner for that patient - Use of a combination of any two of the following (a + b): - a) Placement of an intrauterine device (IUD) or intrauterine system (IUS) - b) Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository - Oral contraception, injected or implanted hormonal methods are not allowed - Fertile males, defined as all males physiologically capable of conceiving offspring, must use a condom during treatment, for 5 T1/2 (8 days) after stopping treatment and for an additional 12 weeks (3 months in total after study drug discontinuation) and should not father a child in this period - Known diagnosis of human immunodeficiency virus (HIV) infection - History of another malignancy within 3 years, except cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix - Patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator - Patient has acute viral hepatitis or a history of chronic or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, (typically defined by elevated AST/ALT [persistent or intermittent], high HBV deoxyribonucleic acid [DNA] level hepatitis B virus surface protein antigen [HBsAg] positive, or high HCV ribonucleic acid [RNA] level) (testing not mandatory) Inclusion Criteria: - Patients who have signed a written informed consent - Patients must have a histologic or cytologic diagnosis of advanced, nonsquamous NSCLC (stage IV by American Joint Committee on Cancer [AJCC] 7th edition [ed.]) - Patients should not have received prior systemic chemotherapy for metastatic disease (prior epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK], kinase inhibitor therapy is allowed); prior adjuvant or neoadjuvant therapy for early stage disease is allowed if received >= 12 months prior to study entry - Prior radiation therapy is allowed to < 25% of the bone marrow; prior radiation must be completed at least 2 weeks prior to day 1 of cycle 1, and patients must have recovered from the acute toxic effects - Eastern Cooperative Oncology Group (ECOG) performance status =< 2 - Patients must have at least one site of measurable disease (per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) - Absolute neutrophil count (ANC) >= 1.5 x 10^9/L - Platelets >= 100 x 10^9/L - Hemoglobin (Hb) > 9 g/dL - Total calcium (corrected for serum albumin) within normal limits (bisphosphonate use for malignant hypercalcemia control is not allowed) - Magnesium >= the lower limit of normal (LLN) - Potassium within normal limits for the institution - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range (or =< 3 x upper limit of normal [ULN] if liver metastases are present) - Serum bilirubin within normal range (or =< 1.5 x ULN if liver metastases are present) - Serum creatinine =< 1.5 x ULN or calculated or 24-hour clearance >= 45 mL/min (calculated creatinine clearance based on Cockcroft-Gault formula) - Serum phosphorus >= LLN - Serum amylase =< ULN - Serum lipase =< ULN - Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L) - Negative serum pregnancy test within 72 hours before starting study treatment in women with childbearing potential - International normalized ratio (INR) =< 2 Exclusion Criteria: - Patients who have received prior treatment with a P13K inhibitor or mammalian target of rapamycin (mTOR)-directed inhibitor - Patients with a known hypersensitivity of BKM120 or to its excipients - Patients with anaplastic lymphoma kinase (ALK) rearrangement or an activating epidermal growth factor receptor (EGFR) mutation who have not received and progressed on appropriate tyrosine kinase inhibitor therapy - Patients with untreated brain metastases are excluded; however, patients with metastatic central nervous system (CNS) tumors may participate in this trial, if the patient is > 2 weeks from therapy completion (incl. --- P13K ---

28 The Impact of Activated p-AKT Expression on Clinical Outcomes in Malignant Lymphoma : A Clinicopathological Study

PI3K(phosphatidylinositol 3-kinase)/AKT pathway is an important oncogenic signaling pathway. However, clinical information about the significance of p-AKT expression in malignant lymphoma is not fully understood yet. In this study, we investigated the overexpression of p-AKT and its prognostic implication in malignant lymphoma.

NCT01789060 Malignant Lymphoma P13K-AKT Pathway Deregulation Other: p-AKT immunohistochemical staining

MeSH:Lymphoma

HPO:Lymphoma

Primary central nervous system lymphoma was excluded in this study Malignant Lymphoma P13K-AKT Pathway Deregulation Lymphoma Recently, among diverse oncogenic signaling pathways, a number of studies have focused on the significance of oncogenic PI3K/AKT (phophatidylinositol 3-kinase/serine-threonine kinase, also known as protein kinase B [PKB]) pathway. --- P13K ---

29 A Phase 2 Study of Panitumumab in Patients With Cetuximab-refractory Metastatic Colorectal Cancer

The purpose of this study is to assess if panitumumab is active enough to warrant comparative studies in patients with metastatic colorectal cancer that has progressed after treatment with cetuximab.

NCT01801904 Metastatic Colorectal Cancer Drug: Panitumumab

MeSH:Colorectal Neoplasms

HPO:Neoplasm of the large intestine

exploratory analysis of tumor-tissue for biological or genomic determinants of outcome of BRAF and P13K mutation status, EGFR and PTEN expression status. --- P13K ---

30 A Biomarker Driven Pilot Study of the Pan-class I PI3K Inhibitor NVP-BKM120 in Combination With Cetuximab in Patients With Recurrent/Metastatic Head and Neck Cancer

This pilot randomized phase I/II trial studies the side effects and best dose of PI3K inhibitor BKM120 when given together with cetuximab and to see how well it works in treating patients with recurrent or metastatic head and neck cancer. PI3K inhibitor BKM120 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumors to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving PI3K inhibitor BKM120 together with cetuximab may kill more tumor cells

NCT01816984 Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma Recurrent Metastatic Squamous Neck Cancer With Occult Primary Recurrent Salivary Gland Cancer Recurrent Squamous Cell Carcinoma of the Hypopharynx Recurrent Squamous Cell Carcinoma of the Larynx Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity Recurrent Squamous Cell Carcinoma of the Nasopharynx Recurrent Squamous Cell Carcinoma of the Oropharynx Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity Recurrent Verrucous Carcinoma of the Larynx Recurrent Verrucous Carcinoma of the Oral Cavity Salivary Gland Squamous Cell Carcinoma Stage IV Squamous Cell Carcinoma of the Hypopharynx Stage IV Squamous Cell Carcinoma of the Nasopharynx Stage IVA Salivary Gland Cancer Stage IVA Squamous Cell Carcinoma of the Larynx Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity Stage IVA Squamous Cell Carcinoma of the Oropharynx Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity Stage IVA Verrucous Stage IVA Verrucous Carcinoma of the Larynx Stage IVA Verrucous Carcinoma of the Oral Cavity Stage IVB Salivary Gland Cancer Stage IVB Squamous Cell Carcinoma of the Larynx Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity Stage IVB Squamous Cell Carcinoma of the Oropharynx Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity Stage IVB Verrucous Carcinoma of the Larynx Stage IVB Verrucous Carcinoma of the Oral Cavity Stage IVC Salivary Gland Cancer Stage IVC Squamous Cell Carcinoma of the Larynx Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity Stage IVC Squamous Cell Carcinoma of the Oropharynx Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity Stage IVC Verrucous Carcinoma of the Larynx Stage IVC Verrucous Carcinoma of the Oral Cavity Tongue Cancer Drug: PI3K inhibitor BKM120 Biological: cetuximab Other: laboratory biomarker analysis Other: questionnaire administration

MeSH:Carcinoma Carcinoma, Squa Carcinoma, Squamous Cell Head and Neck Neoplasms Laryngeal Neoplasms Oropharyngeal Neoplasms Carcinoma, Verrucous Salivary Gland Neoplasms Nasopharyngeal Carcinoma Paranasal Sinus Neoplasms Neoplasms, Unknown Primary Tongue Neoplasms Laryngeal Diseases

HPO:Carcinoma Neoplasm of head and neck Neoplasm of the larynx Neoplasm of the tongue Paranasal sinus neoplasm Salivary gland neoplasm Squamous cell carcinoma

cisplatin or carboplatin) in a prior line of therapy, or documented intolerance to such an agent - Eastern Cooperative Oncology Group (ECOG) performance status =< 2 - No more than two lines of prior cytotoxic chemotherapy in the recurrent/metastatic (palliative intent) treatment setting - Prior use of cetuximab or another epidermal growth factor receptor (EGFR) inhibitor is allowable and if used as a single agent should not be considered as a cytotoxic chemotherapy - Patients must have at least one site of measurable disease (if applicable) (per RECIST for solid tumors or the appropriate disease classification/criteria for the target population) - Absolute neutrophil count (ANC) >= 1.5 x 10^9/L - Platelets >= 100 x 10^9/L - Hemoglobin (Hb) > 9 g/dL - Total calcium (corrected for serum albumin) within normal limits - Magnesium >= the lower limit of normal for the institution - Potassium within normal limits for the institution - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within 1.5 x normal range (or =< 3.0 x upper limit of normal [ULN] if liver metastases are present) - Serum bilirubin within normal range (or =< 1.5 x ULN if liver metastases are present; or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert syndrome) - Serum creatinine =< 1.5 x ULN or 24-hour clearance >= 50 mL/min - Serum amylase =< ULN - Serum lipase =< ULN - Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L) - Negative serum pregnancy test within 72 hours before starting study treatment in women with childbearing potential - Signed informed consent - International normalized ratio (INR) =< 2.5 Exclusion Criteria: - Patients who have received prior treatment with a P13K inhibitor - No available tumor material for correlative studies - Patients with a known hypersensitivity to BKM120 or to its excipients, or hypersensitivity to cetuximab - More than two prior lines of cytotoxic chemotherapy in the recurrent/metastatic disease setting (palliative treatment intent)(excluding single agent use of an EGFR inhibitor) - Patients with untreated brain metastases are excluded; however, patients with treated brain metastases are eligible if they are > 4 weeks from therapy completion (including radiation and/or surgery), are clinically stable at the time of study entry and are not receiving corticosteroid therapy at the time of study entry - Patients with acute or chronic liver, renal disease or pancreatitis - Patients with the following mood disorders as judged by the Investigator or a psychiatrist, or as a result of patient's mood assessment questionnaire (treating physician to decide on whether to administer questionnaire): - Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others) - >= Common Terminology Criteria for Adverse Events (CTCAE) version 4 (v4) grade 3 anxiety - Meets the cut-off score of >= 10 in the Patient Health Questionnaire 9 (PHQ-9) or a cut-off of >= 15 in the Generalized Anxiety Disorder 7 (GAD-7) mood scale, respectively, or selects a positive response of "1, 2, or 3" to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9) - Patients with diarrhea >= CTCAE v4 grade 2 - Patient has active cardiac disease including any of the following: - History of clinically significant heart failure (previously assessed) with a left ventricular ejection fraction (LVEF) of < 50% as determined by multiple grated acquisition (MUGA) scan or echocardiogram (ECHO) - Corrected QT (QTc) > 480 msec on screening electrocardiogram (ECG) (using the Fridericia QT correction [QTcF] formula) - Angina pectoris that requires the use of anti-anginal medication - Ventricular arrhythmias except for benign premature ventricular contractions - Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication - Conduction abnormality requiring a pacemaker - Valvular disease with document compromise in cardiac function - Symptomatic pericarditis - Patient has a history of cardiac dysfunction including any of the following: - Myocardial infraction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function - History of documented congestive heart failure (New York Heart Association functional classification III-IV) - Documented cardiomyopathy - Patient has poorly controlled diabetes mellitus or steroid-induced diabetes mellitus (hemoglobin A1C [HbA1C] > 7.5%) - Patients with any history of hyperglycemia (elevated blood glucose level on blood chemistries) should be considered for initiation of Metformin treatment (500mg, PO, twice daily) prior to starting BKM120 - Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol - Significant symptomatic deterioration of lung function; if clinically indicated, pulmonary function tests including measures of predicted lung volumes, diffusing capacity of the lung for carbon monoxide (DLCO), oxygen (O2) saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates - Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection); patients with unresolved diarrhea will be excluded as previously indicated - Patients who have been treated with any hematopoietic colony-stimulating growth factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF]) =< 2 weeks prior to starting study drug; erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment, may be continued - Patients who are currently receiving treatment with medication with a known risk to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug - Patients receiving chronic treatment with steroids or another immunosuppressive agent other than specified in exclusion criterion #4 - Note: Topical applications (e.g. --- P13K ---

31 Phase II Multicenter Single-arm Study of BKM120 Plus Capecitabine for Breast Cancer Patients With Brain Metastases

This is a study to determine the safety and effectiveness of BKM120 plus capecitabine in breast cancer patients with brain metastases. Both capecitabine and BMK120 have previously shown activity in patients with breast cancer. Like capecitabine, BMK120 is also effective in crossing the blood brain barrier making it a preferred candidate for its evaluation in patients with metastatic breast cancer (MBC).

NCT02000882 Brain Metastases Breast Cancer Metastatic Breast Cancer Drug: BKM120 Drug: capecitabine Drug: Trastuzumab

MeSH:Breast Neoplasm Breast Neoplasms Neoplasm Metastasis Brain Neoplasms

HPO:Brain neoplasm Breast carcinoma Neoplasm of the breast

Patient is able to swallow and retain oral medication 22. Signed most recent patient informed consent form 23. Signed Patient Authorization Form Exclusion Criteria: 1. Patient received prior treatment with a P13K inhibitor. --- P13K ---

32 A Phase Ib Study of BKM120 With Weekly Cisplatin and Radiotherapy in High Risk Locally Advanced Squamous Cell Cancer of the Head and Neck

This research study is evaluating a drug called buparlisib (BKM120) as a possible treatment for locally advanced head and neck squamous cell cancer.

NCT02113878 Carcinoma, Squamous Cell of Head and Neck HPV Positive Oropharyngeal Squamous Cell Carcinoma Hypopharyngeal Cancer Early Invasive Cervical Squamous Cell Carcinoma Carcinoma of Larynx Cancer of Nasopharynx Drug: BKM120 Drug: Cisplatin Radiation: Intensity-modulated radiotherapy (IMRT)

MeSH:Carcinoma Carcinoma, Squamous Cell Neoplasms, Squamous Cell Hypopharyngeal Neoplasms Squamous Cell Carcinoma of Head and Neck Nasopharyngeal Neoplasms Nasopharyngeal Carcinoma

HPO:Carcinoma Neoplasia of the nasopharynx Squamous cell carcinoma

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range - Serum bilirubin within normal range (or ≤ 1.5 x ULN if liver metastases are present; or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert Syndrome) - Serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50 mL/min - Serum amylase ≤ ULN - Serum lipase ≤ ULN - Fasting plasma glucose ≤ 120 mg/dL (6.7 mmol/L) - Signed informed consent - INR ≤ 2 Exclusion Criteria: - Distant metastatic disease - Less than or equal to 10 pack years of tobacco history - Received prior chemotherapy - Received prior radiation to the head and neck or adjacent anatomical site - Received prior treatment with a P13K inhibitor. --- P13K ---

33 A Phase I Trial of BKM120 in Combination With Weekly Nabpaclitaxel (Abraxane®) in Patients With Advanced Solid Tumors Followed by a Dose Expansion Phase in Patients With Recurrent Endometrial or Recurrent Ovarian Cancer

The purpose of the first part of this study or the dose escalation portion of the study is to determine what dose of BKM120 and Abraxane is safe to give when the two drugs are used at the same time in patients who are diagnosed with a solid cancer. A solid cancer is a cancer that does not involve the blood, bone marrow or lymph nodes. Dose escalation determines the least toxic and most effect dose of this drug combination for treatment. Once this dose is established, it will be used for the dose expansion phase of the study where we will determine the effect of BKM120 and Abraxane in women diagnosed with a recurrent endometrial or ovarian cancer. We will see whether the combination of both drugs improves the response and survival of patients treated on the two drug regimen. Also we will try to find out whether there are changes in tumors that can help us determine what patients are more likely to respond to BKM120 and Abraxane.

NCT02117817 Ovarian Cancer Endometrial Cancer Recurrent Ovarian Cancer Recurrent Endometrial Cancer Drug: BKM120 Drug: Nabpaclitaxel

MeSH:Ovarian Neoplasms Carcinoma, Ovarian Epithelial Endometrial Neoplasms

HPO:Endometrial carcinoma Ovarian neoplasm

- Ability to sign informed consent - INR ≤ 1.5 Exclusion Criteria: - Patients who have received prior treatment with a P13K inhibitor. --- P13K ---

34 Phase I Trial of Cisplatin and Etoposide Plus BKM120 in Advanced Solid Tumors, With an Emphasis on Small Cell Lung Cancer

This phase I trial studies the side effects and the best dose of PI3K inhibitor BKM120 when given together with cisplatin and etoposide in treating patients with advanced solid tumors or small cell lung cancer. Drugs used in chemotherapy, such as cisplatin and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing , or by stopping them from spreading. PI3K inhibitor BKM120 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving PI3K inhibitor BKM120 with cisplatin and etoposide may kill more tumor cells.

NCT02194049 Extensive Stage Small Cell Lung Cancer Unspecified Adult Solid Tumor, Protocol Specific Drug: BKM120 Drug: cisplatin Drug: etoposide

MeSH:Lung Neoplasms Small Cell Lung Carcinoma

HPO:Neoplasm of the lung Small cell lung carcinoma

Pharmacokinetic analysis will use non-linear curve fitting methods to estimate the mean peak concentration.. Inclusion Criteria: - Histological or cytological proven advanced solid tumors - =< 3 chemotherapy regimens for metastatic disease; any number of prior targeted or biologic therapies is allowed; (in the expansion cohort, patients must be chemo naïve) - ECOG performance status =< 2 - Absolute neutrophil count (ANC) >= 1.5 x 10^9/L - Platelets >= 100 x 10^9/L - Hemoglobin (Hb) > 9 g/dL - Total calcium (corrected for serum albumin) within normal limits (bisphosphonate use for malignant hypercalcemia control is not allowed) - Magnesium >= the lower limit of normal - Potassium within normal limits for the institution - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range (or =< 3.0 x upper limit of normal (ULN) if liver metastases are present) - Serum bilirubin within normal range (or =< 1.5 x ULN if liver metastases are present; or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert Syndrome) - Serum creatinine =< 1.5 x ULN or calculated clearance >= 60 mL/min - Serum albumin >= 3 g/dl - Serum amylase =< ULN - Serum lipase =< ULN - Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L) - International normalized ratio (INR) =< 2 - Ability to swallow pills - Negative serum pregnancy test Exclusion Criteria: - Received prior treatment with a P13K inhibitor - Received > 300 mg/m^2 of cisplatin and/or for whom cisplatin would not be beneficial - Prior treatment with any investigational drug within the preceding 3 weeks - Known hypersensitivity to BKM120 or to its excipients - Untreated brain metastases are excluded - Acute or chronic liver, renal disease or pancreatitis - Following mood disorders as judged by the Investigator or a psychiatrist, or as a result of patient's mood assessment questionnaire - Diarrhea >= CTCAE grade 2 - Active cardiac disease - History of cardiac dysfunction - Poorly controlled diabetes mellitus or steroid-induced diabetes mellitus - Other concurrent severe and/or uncontrolled concomitant medical conditions - Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection); patients with unresolved diarrhea will be excluded as previously indicated - Treated with any hematopoietic colony-stimulating growth factors - Currently receiving treatment with medication with a known risk to prolong the QT interval or inducing torsades de pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug - Chronic treatment with steroids or another immunosuppressive agent - Herbal medications and certain fruits within 7 days prior to starting study drug - Treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug - Intravenous chemotherapy or targeted anticancer therapy =< 4 weeks - Any continuous or intermittent oral small molecule therapeutics - Received wide field radiotherapy =< 4 weeks or limited field radiation for palliation =< 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy - Undergone major surgery =< 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy - Currently taking therapeutic doses of warfarin sodium or any other Coumadin-derivative anticoagulant - Women who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control - Known diagnosis of HIV infection - History of another active malignancy - Unable or unwilling to abide by the study protocol or cooperate fully with the investigator treatments Inclusion Criteria: - Histological or cytological proven advanced solid tumors - =< 3 chemotherapy regimens for metastatic disease; any number of prior targeted or biologic therapies is allowed; (in the expansion cohort, patients must be chemo naïve) - ECOG performance status =< 2 - Absolute neutrophil count (ANC) >= 1.5 x 10^9/L - Platelets >= 100 x 10^9/L - Hemoglobin (Hb) > 9 g/dL - Total calcium (corrected for serum albumin) within normal limits (bisphosphonate use for malignant hypercalcemia control is not allowed) - Magnesium >= the lower limit of normal - Potassium within normal limits for the institution - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range (or =< 3.0 x upper limit of normal (ULN) if liver metastases are present) - Serum bilirubin within normal range (or =< 1.5 x ULN if liver metastases are present; or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert Syndrome) - Serum creatinine =< 1.5 x ULN or calculated clearance >= 60 mL/min - Serum albumin >= 3 g/dl - Serum amylase =< ULN - Serum lipase =< ULN - Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L) - International normalized ratio (INR) =< 2 - Ability to swallow pills - Negative serum pregnancy test Exclusion Criteria: - Received prior treatment with a P13K inhibitor - Received > 300 mg/m^2 of cisplatin and/or for whom cisplatin would not be beneficial - Prior treatment with any investigational drug within the preceding 3 weeks - Known hypersensitivity to BKM120 or to its excipients - Untreated brain metastases are excluded - Acute or chronic liver, renal disease or pancreatitis - Following mood disorders as judged by the Investigator or a psychiatrist, or as a result of patient's mood assessment questionnaire - Diarrhea >= CTCAE grade 2 - Active cardiac disease - History of cardiac dysfunction - Poorly controlled diabetes mellitus or steroid-induced diabetes mellitus - Other concurrent severe and/or uncontrolled concomitant medical conditions - Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection); patients with unresolved diarrhea will be excluded as previously indicated - Treated with any hematopoietic colony-stimulating growth factors - Currently receiving treatment with medication with a known risk to prolong the QT interval or inducing torsades de pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug - Chronic treatment with steroids or another immunosuppressive agent - Herbal medications and certain fruits within 7 days prior to starting study drug - Treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug - Intravenous chemotherapy or targeted anticancer therapy =< 4 weeks - Any continuous or intermittent oral small molecule therapeutics - Received wide field radiotherapy =< 4 weeks or limited field radiation for palliation =< 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy - Undergone major surgery =< 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy - Currently taking therapeutic doses of warfarin sodium or any other Coumadin-derivative anticoagulant - Women who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control - Known diagnosis of HIV infection - History of another active malignancy - Unable or unwilling to abide by the study protocol or cooperate fully with the investigator treatments Extensive Stage Small Cell Lung Cancer Unspecified Adult Solid Tumor, Protocol Specific Lung Neoplasms Small Cell Lung Carcinoma PRIMARY OBJECTIVES: I. To determine the safety and feasibility of combining BKM120 (PI3K inhibitor BKM120) with cisplatin and etoposide in advanced solid tumors, with emphasis on small cell lung cancer (SCLC). --- P13K ---

Pharmacokinetic analysis will use non-linear curve fitting methods to estimate the mean peak concentration.. Inclusion Criteria: - Histological or cytological proven advanced solid tumors - =< 3 chemotherapy regimens for metastatic disease; any number of prior targeted or biologic therapies is allowed; (in the expansion cohort, patients must be chemo naïve) - ECOG performance status =< 2 - Absolute neutrophil count (ANC) >= 1.5 x 10^9/L - Platelets >= 100 x 10^9/L - Hemoglobin (Hb) > 9 g/dL - Total calcium (corrected for serum albumin) within normal limits (bisphosphonate use for malignant hypercalcemia control is not allowed) - Magnesium >= the lower limit of normal - Potassium within normal limits for the institution - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range (or =< 3.0 x upper limit of normal (ULN) if liver metastases are present) - Serum bilirubin within normal range (or =< 1.5 x ULN if liver metastases are present; or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert Syndrome) - Serum creatinine =< 1.5 x ULN or calculated clearance >= 60 mL/min - Serum albumin >= 3 g/dl - Serum amylase =< ULN - Serum lipase =< ULN - Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L) - International normalized ratio (INR) =< 2 - Ability to swallow pills - Negative serum pregnancy test Exclusion Criteria: - Received prior treatment with a P13K inhibitor - Received > 300 mg/m^2 of cisplatin and/or for whom cisplatin would not be beneficial - Prior treatment with any investigational drug within the preceding 3 weeks - Known hypersensitivity to BKM120 or to its excipients - Untreated brain metastases are excluded - Acute or chronic liver, renal disease or pancreatitis - Following mood disorders as judged by the Investigator or a psychiatrist, or as a result of patient's mood assessment questionnaire - Diarrhea >= CTCAE grade 2 - Active cardiac disease - History of cardiac dysfunction - Poorly controlled diabetes mellitus or steroid-induced diabetes mellitus - Other concurrent severe and/or uncontrolled concomitant medical conditions - Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection); patients with unresolved diarrhea will be excluded as previously indicated - Treated with any hematopoietic colony-stimulating growth factors - Currently receiving treatment with medication with a known risk to prolong the QT interval or inducing torsades de pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug - Chronic treatment with steroids or another immunosuppressive agent - Herbal medications and certain fruits within 7 days prior to starting study drug - Treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug - Intravenous chemotherapy or targeted anticancer therapy =< 4 weeks - Any continuous or intermittent oral small molecule therapeutics - Received wide field radiotherapy =< 4 weeks or limited field radiation for palliation =< 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy - Undergone major surgery =< 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy - Currently taking therapeutic doses of warfarin sodium or any other Coumadin-derivative anticoagulant - Women who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control - Known diagnosis of HIV infection - History of another active malignancy - Unable or unwilling to abide by the study protocol or cooperate fully with the investigator treatments Inclusion Criteria: - Histological or cytological proven advanced solid tumors - =< 3 chemotherapy regimens for metastatic disease; any number of prior targeted or biologic therapies is allowed; (in the expansion cohort, patients must be chemo naïve) - ECOG performance status =< 2 - Absolute neutrophil count (ANC) >= 1.5 x 10^9/L - Platelets >= 100 x 10^9/L - Hemoglobin (Hb) > 9 g/dL - Total calcium (corrected for serum albumin) within normal limits (bisphosphonate use for malignant hypercalcemia control is not allowed) - Magnesium >= the lower limit of normal - Potassium within normal limits for the institution - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range (or =< 3.0 x upper limit of normal (ULN) if liver metastases are present) - Serum bilirubin within normal range (or =< 1.5 x ULN if liver metastases are present; or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert Syndrome) - Serum creatinine =< 1.5 x ULN or calculated clearance >= 60 mL/min - Serum albumin >= 3 g/dl - Serum amylase =< ULN - Serum lipase =< ULN - Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L) - International normalized ratio (INR) =< 2 - Ability to swallow pills - Negative serum pregnancy test Exclusion Criteria: - Received prior treatment with a P13K inhibitor - Received > 300 mg/m^2 of cisplatin and/or for whom cisplatin would not be beneficial - Prior treatment with any investigational drug within the preceding 3 weeks - Known hypersensitivity to BKM120 or to its excipients - Untreated brain metastases are excluded - Acute or chronic liver, renal disease or pancreatitis - Following mood disorders as judged by the Investigator or a psychiatrist, or as a result of patient's mood assessment questionnaire - Diarrhea >= CTCAE grade 2 - Active cardiac disease - History of cardiac dysfunction - Poorly controlled diabetes mellitus or steroid-induced diabetes mellitus - Other concurrent severe and/or uncontrolled concomitant medical conditions - Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection); patients with unresolved diarrhea will be excluded as previously indicated - Treated with any hematopoietic colony-stimulating growth factors - Currently receiving treatment with medication with a known risk to prolong the QT interval or inducing torsades de pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug - Chronic treatment with steroids or another immunosuppressive agent - Herbal medications and certain fruits within 7 days prior to starting study drug - Treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug - Intravenous chemotherapy or targeted anticancer therapy =< 4 weeks - Any continuous or intermittent oral small molecule therapeutics - Received wide field radiotherapy =< 4 weeks or limited field radiation for palliation =< 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy - Undergone major surgery =< 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy - Currently taking therapeutic doses of warfarin sodium or any other Coumadin-derivative anticoagulant - Women who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control - Known diagnosis of HIV infection - History of another active malignancy - Unable or unwilling to abide by the study protocol or cooperate fully with the investigator treatments Extensive Stage Small Cell Lung Cancer Unspecified Adult Solid Tumor, Protocol Specific Lung Neoplasms Small Cell Lung Carcinoma PRIMARY OBJECTIVES: I. To determine the safety and feasibility of combining BKM120 (PI3K inhibitor BKM120) with cisplatin and etoposide in advanced solid tumors, with emphasis on small cell lung cancer (SCLC). --- P13K --- --- P13K ---

35 A Phase II Study of BKM120 (Buparlisib) in Relapsed or Refractory Thymomas

Thymic tumors are rare tumors, but represent the most common tumors of the anterior mediastinum. Thymoma has an indolent course in advanced disease and has the propensity to spread to the pleura. In first line therapy, combination chemotherapy produces responses in approximately 80% of patients. A number of single agents have activity in recurrent disease, but none are curable. Patients with recurrent thymoma have limited treatment options, and thus novel target modalities are needed. At the Indiana University Simon Cancer Center (IUSCC), more patients with advance thymoma are seen than any other institution in the country. Our main hypothesis is the PI3K pathway is an important driver for growth and metastasis of thymoma and that inhibition of the PI3K pathway is expected to produce clinically meaningful response in patients with recurrent thymoma.

NCT02220855 Thymoma Drug: BKM120

MeSH:Thymoma Thymus Neoplasms

HPO:Neoplasm of the thymus Thymoma

Signed informed consent 22. INR ≤ 2 Exclusion Criteria: 1. Patients who have received prior treatment with a P13K inhibitor. --- P13K ---

36 An Open-Label Pilot Study to Evaluate the Efficacy and Safety of a Combination Treatment of Sonidegib (LDE225) and Buparlisib (BKM120) For the Treatment of Advanced Basal Cell Carcinomas

This pilot trial studies how well sonidegib and buparlisib work in treating patients with basal cell carcinoma that has spread to other places in the body. Sonidegib and buparlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

NCT02303041 Carcinoma, Basal Cell Recurrent Skin Cancer Skin Neoplasms Basal Cell Nevus Syndrome Drug: Buparlisib Drug: Sonidegib

MeSH:Carcinoma Carcinoma, Basal Cell Skin Neoplasms Basal Cell Nevus Syndrome

HPO:Basal cell carcinoma Carcinoma Neoplasm of the skin

The gene expression profiles for Gli-1; Gli-2; "Patched" (Ptch) ; "Suppressor of Fused" (SuFu); "Smoothened" (Smo)"; and phosphatidylinositol-3-kinase (PI3K) were to be correlated to the clinical response to therapeutic therapy.. INCLUSION CRITERIA: - Able to understand and sign informed consent - Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 - Metastatic BCC, histologic confirmation of distant BCC metastasis - Metastatic disease, target lesion must be measurable using computed tomography (CT) or magnetic resonance imaging (MRI) - Locally advanced BCC are required to have disease that is considered inoperable due to significant functional compromise or to have a medical contraindication to surgery - Nevoid BCC syndrome (Gorlin syndrome) may enroll in this study but must meet the criteria for locally advanced or metastatic disease listed above - COHORT 2 ONLY: A Smoothened inhibitor must have been previously administered as monotherapy - Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L - Platelets ≥ 80 x10^9/L - Hemoglobin (Hb) > 9 g/dL or values ≥ lower limit of normal (LLN) for site-specific lab - Total calcium (corrected for serum albumin) within normal limits (biphosphonate use for malignant hypercalcemia control is not allowed) - Magnesium ≥ the lower limit of normal - Potassium within normal limits for the institution - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range [or ≤ 3.0 x upper limit of normal (ULN) if liver metastases are present] - Serum bilirubin within normal range (or ≤ 1.5 x ULN if liver metastases are present; or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in patients with well-documented Gilbert Syndrome) - Serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50 mL/min - Serum amylase ≤ ULN - Serum lipase ≤ ULN - Fasting plasma glucose ≤ 120 mg/dL (6.7 mmol/L) - Negative serum pregnancy test within 72 hours before starting study treatment in women with childbearing potential - International normalized ratio (INR) ≤ 2 EXCLUSION CRITERIA: - Prior treatment with a P13K inhibitor - Known hypersensitivity to buparlisib or to its excipients - Untreated brain metastases are excluded; however, patients with metastatic central nervous system (CNS) tumors may participate in this trial, if the patient is > 4 weeks from therapy completion (including radiation and/or surgery), is clinically stable at the time of study entry and is not receiving corticosteroid therapy - Acute or chronic liver, renal disease or pancreatitis - Baseline creatinine kinase (CK) > ULN - The following mood disorders as judged by the Investigator or a psychiatrist, or as a result of patient's mood assessment questionnaire: - Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others) - ≥ Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety - Meets the cut-off score of ≥ 12 in the Patient Health Questionnaire (PHQ)-9 or a cut-off of ≥ 15 in the Generalized Anxiety Disorder 7-item (GAD-7) mood scale, respectively, or selects a positive response of "1, 2, or 3" to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9) - Diarrhea ≥ CTCAE grade 2 - Active cardiac disease including any of the following: - Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) - QTc > 450 msec on screening electrocardiogram (ECG) (using the QTcF formula) - Angina pectoris that requires the use of anti-anginal medication - Ventricular arrhythmias except for benign premature ventricular contractions - Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication - Conduction abnormality requiring a pacemaker - Valvular disease with document compromise in cardiac function - Symptomatic pericarditis - Patient has a history of cardiac dysfunction including any of the following: - Myocardial infraction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function - History of documented congestive heart failure (New York Heart Association functional classification 3-4) - Documented cardiomyopathy - Patient has poorly controlled diabetes mellitus [defined as hemoglobin A1C (HgA1c) > ULN], steroid-induced diabetes mellitus, or insulin dependent diabetes mellitus - Other concurrent severe and/or uncontrolled concomitant medical conditions (eg, active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol - Significant symptomatic deterioration of lung function; if clinically indicated, pulmonary function tests including measures of predicted lung volumes, diffusing capacity of the lung for carbon monoxide (DLco), oxygen (O2) saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates - Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of buparlisib (eg, ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection); patients with unresolved diarrhea will be excluded as previously indicated - Patients who have been treated with any hematopoietic colony-stimulating growth factors (eg, filgrastim (granulocyte-colony stimulating factor, G-CSF), sargramostim (granulocyte-macrophage colony-stimulating factor, GM-CSF) ≤ 2 weeks prior to starting study drug; erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment, may be continued - Patients who are currently receiving treatment with medication with a known risk to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug - Patients receiving chronic treatment with steroids or another immunosuppressive agent - Note: topical applications (eg, rash), inhaled sprays (eg, obstructive airways diseases), eye drops or local injections (eg, intr-articular) are allowed; patients with previously treated brain metastases, who are on stable low dose corticosteroids treatment (eg, dexamethasone 2 mg/day, prednisolone 10 mg/day) for at least 14 days before start of study treatment are eligible - Patients who have taken herbal medications and certain fruits within 7 days prior to starting study drug; herbal medications include, but are not limited to St. John's Wort, Kava, ephedra (ma huang), dehydroepiandrosterone (DHEA), gingko biloba, yohimbe, saw palmetto, and ginseng; fruits include the cytochrome P450, family 3, subfamily A (CYP3A) inhibitors Seville oranges, grapefruit, pummelos, or exotic citrus fruits - Patients who are currently treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug; please note that co-treatment with weak inhibitors of CYP3A is allowed - Patients who have received chemotherapy or targeted anticancer therapy ≤ 4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug must recover to a grade 1 before starting the trial - Patients who have received any continuous or intermittent small molecule therapeutics (excluding monoclonal antibodies) ≤ 5 effective half lives prior to starting study drug or who have not recovered from side effects of such therapy - Use of statin drugs or other medications known to associate with rhabdomyolysis; these drugs must be discontinued at enrollment - Patients who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy - Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy - Patients who are currently taking therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulant; low molecular weight heparin is allowed - Women who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control; double barrier contraceptives must be used through the trial by both sexes; oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study; women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (ie, who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test ≤ 72 hours prior to initiating treatment - Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (eg, age appropriate, history of vasomotor symptoms) or 6 months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels > 40 mIU/mL (for US only: and estradiol < 20 pg/mL) or have had surgical bilateral oophorectomy (with or without hysterectomy) at least 6 weeks prior; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential - Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during the study and through 20 months after the final dose of study treatment; for males with partners with childbearing potential, highly effective contraception is required for 6 months; the highly effective contraception is defined as either: - True abstinence: when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception - Sterilization: have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment - Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate); for female subjects on the study, the vasectomized male partner should be the sole partner for that patient - Use of a combination of any two of the following (a+b): - a. Placement of an intrauterine device (IUD) or intrauterine system (IUS) - b. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository - Oral contraception, injected or implanted hormonal methods are not allowed - Fertile males, must use highly effective (double barrier) methods of contraception (eg, spermicidal gel plus condom) for the entire duration of the study, and continuing using contraception and refrain from fathering a child for 6 months following the study drug; a condom is required to be used also by vasectomized men as well as during intercourse with a male partner in order to prevent delivery of the study treatment via seminal fluid; female partner of male study subject should use highly effective contraception during dosing of any study agent and for 16 weeks after final dose of study therapy - Note: hormonal contraception methods (eg, oral, injected, implanted) are not allowed - Note: woman are considered post-menopausal and not child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (eg, age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol < 20 pg/mL or have had surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential - Known diagnosis of human immunodeficiency virus (HIV) infection, hepatitis B or hepatitis C - History of another malignancy within 3 years, except cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix - Patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator INCLUSION CRITERIA: - Able to understand and sign informed consent - Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 - Metastatic BCC, histologic confirmation of distant BCC metastasis - Metastatic disease, target lesion must be measurable using computed tomography (CT) or magnetic resonance imaging (MRI) - Locally advanced BCC are required to have disease that is considered inoperable due to significant functional compromise or to have a medical contraindication to surgery - Nevoid BCC syndrome (Gorlin syndrome) may enroll in this study but must meet the criteria for locally advanced or metastatic disease listed above - COHORT 2 ONLY: A Smoothened inhibitor must have been previously administered as monotherapy - Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L - Platelets ≥ 80 x10^9/L - Hemoglobin (Hb) > 9 g/dL or values ≥ lower limit of normal (LLN) for site-specific lab - Total calcium (corrected for serum albumin) within normal limits (biphosphonate use for malignant hypercalcemia control is not allowed) - Magnesium ≥ the lower limit of normal - Potassium within normal limits for the institution - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range [or ≤ 3.0 x upper limit of normal (ULN) if liver metastases are present] - Serum bilirubin within normal range (or ≤ 1.5 x ULN if liver metastases are present; or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in patients with well-documented Gilbert Syndrome) - Serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50 mL/min - Serum amylase ≤ ULN - Serum lipase ≤ ULN - Fasting plasma glucose ≤ 120 mg/dL (6.7 mmol/L) - Negative serum pregnancy test within 72 hours before starting study treatment in women with childbearing potential - International normalized ratio (INR) ≤ 2 EXCLUSION CRITERIA: - Prior treatment with a P13K inhibitor - Known hypersensitivity to buparlisib or to its excipients - Untreated brain metastases are excluded; however, patients with metastatic central nervous system (CNS) tumors may participate in this trial, if the patient is > 4 weeks from therapy completion (including radiation and/or surgery), is clinically stable at the time of study entry and is not receiving corticosteroid therapy - Acute or chronic liver, renal disease or pancreatitis - Baseline creatinine kinase (CK) > ULN - The following mood disorders as judged by the Investigator or a psychiatrist, or as a result of patient's mood assessment questionnaire: - Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others) - ≥ Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety - Meets the cut-off score of ≥ 12 in the Patient Health Questionnaire (PHQ)-9 or a cut-off of ≥ 15 in the Generalized Anxiety Disorder 7-item (GAD-7) mood scale, respectively, or selects a positive response of "1, 2, or 3" to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9) - Diarrhea ≥ CTCAE grade 2 - Active cardiac disease including any of the following: - Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) - QTc > 450 msec on screening electrocardiogram (ECG) (using the QTcF formula) - Angina pectoris that requires the use of anti-anginal medication - Ventricular arrhythmias except for benign premature ventricular contractions - Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication - Conduction abnormality requiring a pacemaker - Valvular disease with document compromise in cardiac function - Symptomatic pericarditis - Patient has a history of cardiac dysfunction including any of the following: - Myocardial infraction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function - History of documented congestive heart failure (New York Heart Association functional classification 3-4) - Documented cardiomyopathy - Patient has poorly controlled diabetes mellitus [defined as hemoglobin A1C (HgA1c) > ULN], steroid-induced diabetes mellitus, or insulin dependent diabetes mellitus - Other concurrent severe and/or uncontrolled concomitant medical conditions (eg, active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol - Significant symptomatic deterioration of lung function; if clinically indicated, pulmonary function tests including measures of predicted lung volumes, diffusing capacity of the lung for carbon monoxide (DLco), oxygen (O2) saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates - Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of buparlisib (eg, ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection); patients with unresolved diarrhea will be excluded as previously indicated - Patients who have been treated with any hematopoietic colony-stimulating growth factors (eg, filgrastim (granulocyte-colony stimulating factor, G-CSF), sargramostim (granulocyte-macrophage colony-stimulating factor, GM-CSF) ≤ 2 weeks prior to starting study drug; erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment, may be continued - Patients who are currently receiving treatment with medication with a known risk to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug - Patients receiving chronic treatment with steroids or another immunosuppressive agent - Note: topical applications (eg, rash), inhaled sprays (eg, obstructive airways diseases), eye drops or local injections (eg, intr-articular) are allowed; patients with previously treated brain metastases, who are on stable low dose corticosteroids treatment (eg, dexamethasone 2 mg/day, prednisolone 10 mg/day) for at least 14 days before start of study treatment are eligible - Patients who have taken herbal medications and certain fruits within 7 days prior to starting study drug; herbal medications include, but are not limited to St. John's Wort, Kava, ephedra (ma huang), dehydroepiandrosterone (DHEA), gingko biloba, yohimbe, saw palmetto, and ginseng; fruits include the cytochrome P450, family 3, subfamily A (CYP3A) inhibitors Seville oranges, grapefruit, pummelos, or exotic citrus fruits - Patients who are currently treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug; please note that co-treatment with weak inhibitors of CYP3A is allowed - Patients who have received chemotherapy or targeted anticancer therapy ≤ 4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug must recover to a grade 1 before starting the trial - Patients who have received any continuous or intermittent small molecule therapeutics (excluding monoclonal antibodies) ≤ 5 effective half lives prior to starting study drug or who have not recovered from side effects of such therapy - Use of statin drugs or other medications known to associate with rhabdomyolysis; these drugs must be discontinued at enrollment - Patients who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy - Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy - Patients who are currently taking therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulant; low molecular weight heparin is allowed - Women who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control; double barrier contraceptives must be used through the trial by both sexes; oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study; women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (ie, who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test ≤ 72 hours prior to initiating treatment - Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (eg, age appropriate, history of vasomotor symptoms) or 6 months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels > 40 mIU/mL (for US only: and estradiol < 20 pg/mL) or have had surgical bilateral oophorectomy (with or without hysterectomy) at least 6 weeks prior; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential - Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during the study and through 20 months after the final dose of study treatment; for males with partners with childbearing potential, highly effective contraception is required for 6 months; the highly effective contraception is defined as either: - True abstinence: when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception - Sterilization: have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment - Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate); for female subjects on the study, the vasectomized male partner should be the sole partner for that patient - Use of a combination of any two of the following (a+b): - a. Placement of an intrauterine device (IUD) or intrauterine system (IUS) - b. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository - Oral contraception, injected or implanted hormonal methods are not allowed - Fertile males, must use highly effective (double barrier) methods of contraception (eg, spermicidal gel plus condom) for the entire duration of the study, and continuing using contraception and refrain from fathering a child for 6 months following the study drug; a condom is required to be used also by vasectomized men as well as during intercourse with a male partner in order to prevent delivery of the study treatment via seminal fluid; female partner of male study subject should use highly effective contraception during dosing of any study agent and for 16 weeks after final dose of study therapy - Note: hormonal contraception methods (eg, oral, injected, implanted) are not allowed - Note: woman are considered post-menopausal and not child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (eg, age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol < 20 pg/mL or have had surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential - Known diagnosis of human immunodeficiency virus (HIV) infection, hepatitis B or hepatitis C - History of another malignancy within 3 years, except cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix - Patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator Carcinoma, Basal Cell Recurrent Skin Cancer Skin Neoplasms Basal Cell Nevus Syndrome Carcinoma Carcinoma, Basal Cell Skin Neoplasms Basal Cell Nevus Syndrome PRIMARY OBJECTIVES: Estimate the overall response rate (ORR) of sonidegib (erismodegib) in combination with buparlisib (hereby referred to as "LB therapy") for patients with locally advanced or metastatic basal cell carcinoma (BCC) in Smoothened inhibitor-naive patients (Cohort 1) and those whose disease is refractory or relapsed on Smoothened inhibitor monotherapy (Cohort 2). --- P13K ---

The gene expression profiles for Gli-1; Gli-2; "Patched" (Ptch) ; "Suppressor of Fused" (SuFu); "Smoothened" (Smo)"; and phosphatidylinositol-3-kinase (PI3K) were to be correlated to the clinical response to therapeutic therapy.. INCLUSION CRITERIA: - Able to understand and sign informed consent - Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 - Metastatic BCC, histologic confirmation of distant BCC metastasis - Metastatic disease, target lesion must be measurable using computed tomography (CT) or magnetic resonance imaging (MRI) - Locally advanced BCC are required to have disease that is considered inoperable due to significant functional compromise or to have a medical contraindication to surgery - Nevoid BCC syndrome (Gorlin syndrome) may enroll in this study but must meet the criteria for locally advanced or metastatic disease listed above - COHORT 2 ONLY: A Smoothened inhibitor must have been previously administered as monotherapy - Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L - Platelets ≥ 80 x10^9/L - Hemoglobin (Hb) > 9 g/dL or values ≥ lower limit of normal (LLN) for site-specific lab - Total calcium (corrected for serum albumin) within normal limits (biphosphonate use for malignant hypercalcemia control is not allowed) - Magnesium ≥ the lower limit of normal - Potassium within normal limits for the institution - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range [or ≤ 3.0 x upper limit of normal (ULN) if liver metastases are present] - Serum bilirubin within normal range (or ≤ 1.5 x ULN if liver metastases are present; or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in patients with well-documented Gilbert Syndrome) - Serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50 mL/min - Serum amylase ≤ ULN - Serum lipase ≤ ULN - Fasting plasma glucose ≤ 120 mg/dL (6.7 mmol/L) - Negative serum pregnancy test within 72 hours before starting study treatment in women with childbearing potential - International normalized ratio (INR) ≤ 2 EXCLUSION CRITERIA: - Prior treatment with a P13K inhibitor - Known hypersensitivity to buparlisib or to its excipients - Untreated brain metastases are excluded; however, patients with metastatic central nervous system (CNS) tumors may participate in this trial, if the patient is > 4 weeks from therapy completion (including radiation and/or surgery), is clinically stable at the time of study entry and is not receiving corticosteroid therapy - Acute or chronic liver, renal disease or pancreatitis - Baseline creatinine kinase (CK) > ULN - The following mood disorders as judged by the Investigator or a psychiatrist, or as a result of patient's mood assessment questionnaire: - Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others) - ≥ Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety - Meets the cut-off score of ≥ 12 in the Patient Health Questionnaire (PHQ)-9 or a cut-off of ≥ 15 in the Generalized Anxiety Disorder 7-item (GAD-7) mood scale, respectively, or selects a positive response of "1, 2, or 3" to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9) - Diarrhea ≥ CTCAE grade 2 - Active cardiac disease including any of the following: - Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) - QTc > 450 msec on screening electrocardiogram (ECG) (using the QTcF formula) - Angina pectoris that requires the use of anti-anginal medication - Ventricular arrhythmias except for benign premature ventricular contractions - Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication - Conduction abnormality requiring a pacemaker - Valvular disease with document compromise in cardiac function - Symptomatic pericarditis - Patient has a history of cardiac dysfunction including any of the following: - Myocardial infraction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function - History of documented congestive heart failure (New York Heart Association functional classification 3-4) - Documented cardiomyopathy - Patient has poorly controlled diabetes mellitus [defined as hemoglobin A1C (HgA1c) > ULN], steroid-induced diabetes mellitus, or insulin dependent diabetes mellitus - Other concurrent severe and/or uncontrolled concomitant medical conditions (eg, active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol - Significant symptomatic deterioration of lung function; if clinically indicated, pulmonary function tests including measures of predicted lung volumes, diffusing capacity of the lung for carbon monoxide (DLco), oxygen (O2) saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates - Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of buparlisib (eg, ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection); patients with unresolved diarrhea will be excluded as previously indicated - Patients who have been treated with any hematopoietic colony-stimulating growth factors (eg, filgrastim (granulocyte-colony stimulating factor, G-CSF), sargramostim (granulocyte-macrophage colony-stimulating factor, GM-CSF) ≤ 2 weeks prior to starting study drug; erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment, may be continued - Patients who are currently receiving treatment with medication with a known risk to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug - Patients receiving chronic treatment with steroids or another immunosuppressive agent - Note: topical applications (eg, rash), inhaled sprays (eg, obstructive airways diseases), eye drops or local injections (eg, intr-articular) are allowed; patients with previously treated brain metastases, who are on stable low dose corticosteroids treatment (eg, dexamethasone 2 mg/day, prednisolone 10 mg/day) for at least 14 days before start of study treatment are eligible - Patients who have taken herbal medications and certain fruits within 7 days prior to starting study drug; herbal medications include, but are not limited to St. John's Wort, Kava, ephedra (ma huang), dehydroepiandrosterone (DHEA), gingko biloba, yohimbe, saw palmetto, and ginseng; fruits include the cytochrome P450, family 3, subfamily A (CYP3A) inhibitors Seville oranges, grapefruit, pummelos, or exotic citrus fruits - Patients who are currently treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug; please note that co-treatment with weak inhibitors of CYP3A is allowed - Patients who have received chemotherapy or targeted anticancer therapy ≤ 4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug must recover to a grade 1 before starting the trial - Patients who have received any continuous or intermittent small molecule therapeutics (excluding monoclonal antibodies) ≤ 5 effective half lives prior to starting study drug or who have not recovered from side effects of such therapy - Use of statin drugs or other medications known to associate with rhabdomyolysis; these drugs must be discontinued at enrollment - Patients who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy - Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy - Patients who are currently taking therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulant; low molecular weight heparin is allowed - Women who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control; double barrier contraceptives must be used through the trial by both sexes; oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study; women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (ie, who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test ≤ 72 hours prior to initiating treatment - Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (eg, age appropriate, history of vasomotor symptoms) or 6 months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels > 40 mIU/mL (for US only: and estradiol < 20 pg/mL) or have had surgical bilateral oophorectomy (with or without hysterectomy) at least 6 weeks prior; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential - Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during the study and through 20 months after the final dose of study treatment; for males with partners with childbearing potential, highly effective contraception is required for 6 months; the highly effective contraception is defined as either: - True abstinence: when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception - Sterilization: have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment - Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate); for female subjects on the study, the vasectomized male partner should be the sole partner for that patient - Use of a combination of any two of the following (a+b): - a. Placement of an intrauterine device (IUD) or intrauterine system (IUS) - b. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository - Oral contraception, injected or implanted hormonal methods are not allowed - Fertile males, must use highly effective (double barrier) methods of contraception (eg, spermicidal gel plus condom) for the entire duration of the study, and continuing using contraception and refrain from fathering a child for 6 months following the study drug; a condom is required to be used also by vasectomized men as well as during intercourse with a male partner in order to prevent delivery of the study treatment via seminal fluid; female partner of male study subject should use highly effective contraception during dosing of any study agent and for 16 weeks after final dose of study therapy - Note: hormonal contraception methods (eg, oral, injected, implanted) are not allowed - Note: woman are considered post-menopausal and not child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (eg, age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol < 20 pg/mL or have had surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential - Known diagnosis of human immunodeficiency virus (HIV) infection, hepatitis B or hepatitis C - History of another malignancy within 3 years, except cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix - Patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator INCLUSION CRITERIA: - Able to understand and sign informed consent - Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 - Metastatic BCC, histologic confirmation of distant BCC metastasis - Metastatic disease, target lesion must be measurable using computed tomography (CT) or magnetic resonance imaging (MRI) - Locally advanced BCC are required to have disease that is considered inoperable due to significant functional compromise or to have a medical contraindication to surgery - Nevoid BCC syndrome (Gorlin syndrome) may enroll in this study but must meet the criteria for locally advanced or metastatic disease listed above - COHORT 2 ONLY: A Smoothened inhibitor must have been previously administered as monotherapy - Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L - Platelets ≥ 80 x10^9/L - Hemoglobin (Hb) > 9 g/dL or values ≥ lower limit of normal (LLN) for site-specific lab - Total calcium (corrected for serum albumin) within normal limits (biphosphonate use for malignant hypercalcemia control is not allowed) - Magnesium ≥ the lower limit of normal - Potassium within normal limits for the institution - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range [or ≤ 3.0 x upper limit of normal (ULN) if liver metastases are present] - Serum bilirubin within normal range (or ≤ 1.5 x ULN if liver metastases are present; or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in patients with well-documented Gilbert Syndrome) - Serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50 mL/min - Serum amylase ≤ ULN - Serum lipase ≤ ULN - Fasting plasma glucose ≤ 120 mg/dL (6.7 mmol/L) - Negative serum pregnancy test within 72 hours before starting study treatment in women with childbearing potential - International normalized ratio (INR) ≤ 2 EXCLUSION CRITERIA: - Prior treatment with a P13K inhibitor - Known hypersensitivity to buparlisib or to its excipients - Untreated brain metastases are excluded; however, patients with metastatic central nervous system (CNS) tumors may participate in this trial, if the patient is > 4 weeks from therapy completion (including radiation and/or surgery), is clinically stable at the time of study entry and is not receiving corticosteroid therapy - Acute or chronic liver, renal disease or pancreatitis - Baseline creatinine kinase (CK) > ULN - The following mood disorders as judged by the Investigator or a psychiatrist, or as a result of patient's mood assessment questionnaire: - Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others) - ≥ Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety - Meets the cut-off score of ≥ 12 in the Patient Health Questionnaire (PHQ)-9 or a cut-off of ≥ 15 in the Generalized Anxiety Disorder 7-item (GAD-7) mood scale, respectively, or selects a positive response of "1, 2, or 3" to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9) - Diarrhea ≥ CTCAE grade 2 - Active cardiac disease including any of the following: - Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) - QTc > 450 msec on screening electrocardiogram (ECG) (using the QTcF formula) - Angina pectoris that requires the use of anti-anginal medication - Ventricular arrhythmias except for benign premature ventricular contractions - Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication - Conduction abnormality requiring a pacemaker - Valvular disease with document compromise in cardiac function - Symptomatic pericarditis - Patient has a history of cardiac dysfunction including any of the following: - Myocardial infraction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function - History of documented congestive heart failure (New York Heart Association functional classification 3-4) - Documented cardiomyopathy - Patient has poorly controlled diabetes mellitus [defined as hemoglobin A1C (HgA1c) > ULN], steroid-induced diabetes mellitus, or insulin dependent diabetes mellitus - Other concurrent severe and/or uncontrolled concomitant medical conditions (eg, active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol - Significant symptomatic deterioration of lung function; if clinically indicated, pulmonary function tests including measures of predicted lung volumes, diffusing capacity of the lung for carbon monoxide (DLco), oxygen (O2) saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates - Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of buparlisib (eg, ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection); patients with unresolved diarrhea will be excluded as previously indicated - Patients who have been treated with any hematopoietic colony-stimulating growth factors (eg, filgrastim (granulocyte-colony stimulating factor, G-CSF), sargramostim (granulocyte-macrophage colony-stimulating factor, GM-CSF) ≤ 2 weeks prior to starting study drug; erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment, may be continued - Patients who are currently receiving treatment with medication with a known risk to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug - Patients receiving chronic treatment with steroids or another immunosuppressive agent - Note: topical applications (eg, rash), inhaled sprays (eg, obstructive airways diseases), eye drops or local injections (eg, intr-articular) are allowed; patients with previously treated brain metastases, who are on stable low dose corticosteroids treatment (eg, dexamethasone 2 mg/day, prednisolone 10 mg/day) for at least 14 days before start of study treatment are eligible - Patients who have taken herbal medications and certain fruits within 7 days prior to starting study drug; herbal medications include, but are not limited to St. John's Wort, Kava, ephedra (ma huang), dehydroepiandrosterone (DHEA), gingko biloba, yohimbe, saw palmetto, and ginseng; fruits include the cytochrome P450, family 3, subfamily A (CYP3A) inhibitors Seville oranges, grapefruit, pummelos, or exotic citrus fruits - Patients who are currently treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug; please note that co-treatment with weak inhibitors of CYP3A is allowed - Patients who have received chemotherapy or targeted anticancer therapy ≤ 4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug must recover to a grade 1 before starting the trial - Patients who have received any continuous or intermittent small molecule therapeutics (excluding monoclonal antibodies) ≤ 5 effective half lives prior to starting study drug or who have not recovered from side effects of such therapy - Use of statin drugs or other medications known to associate with rhabdomyolysis; these drugs must be discontinued at enrollment - Patients who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy - Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy - Patients who are currently taking therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulant; low molecular weight heparin is allowed - Women who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control; double barrier contraceptives must be used through the trial by both sexes; oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study; women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (ie, who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test ≤ 72 hours prior to initiating treatment - Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (eg, age appropriate, history of vasomotor symptoms) or 6 months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) levels > 40 mIU/mL (for US only: and estradiol < 20 pg/mL) or have had surgical bilateral oophorectomy (with or without hysterectomy) at least 6 weeks prior; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential - Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during the study and through 20 months after the final dose of study treatment; for males with partners with childbearing potential, highly effective contraception is required for 6 months; the highly effective contraception is defined as either: - True abstinence: when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception - Sterilization: have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment - Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate); for female subjects on the study, the vasectomized male partner should be the sole partner for that patient - Use of a combination of any two of the following (a+b): - a. Placement of an intrauterine device (IUD) or intrauterine system (IUS) - b. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository - Oral contraception, injected or implanted hormonal methods are not allowed - Fertile males, must use highly effective (double barrier) methods of contraception (eg, spermicidal gel plus condom) for the entire duration of the study, and continuing using contraception and refrain from fathering a child for 6 months following the study drug; a condom is required to be used also by vasectomized men as well as during intercourse with a male partner in order to prevent delivery of the study treatment via seminal fluid; female partner of male study subject should use highly effective contraception during dosing of any study agent and for 16 weeks after final dose of study therapy - Note: hormonal contraception methods (eg, oral, injected, implanted) are not allowed - Note: woman are considered post-menopausal and not child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (eg, age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol < 20 pg/mL or have had surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential - Known diagnosis of human immunodeficiency virus (HIV) infection, hepatitis B or hepatitis C - History of another malignancy within 3 years, except cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix - Patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator Carcinoma, Basal Cell Recurrent Skin Cancer Skin Neoplasms Basal Cell Nevus Syndrome Carcinoma Carcinoma, Basal Cell Skin Neoplasms Basal Cell Nevus Syndrome PRIMARY OBJECTIVES: Estimate the overall response rate (ORR) of sonidegib (erismodegib) in combination with buparlisib (hereby referred to as "LB therapy") for patients with locally advanced or metastatic basal cell carcinoma (BCC) in Smoothened inhibitor-naive patients (Cohort 1) and those whose disease is refractory or relapsed on Smoothened inhibitor monotherapy (Cohort 2). --- P13K --- --- P13K ---

37 A Phase I/II Study of PI3Kinase Inhibition (Copanlisib) and Anti-PD-1 Antibody Nivolumab in Relapsed/Refractory Solid Tumors With Expansions in Mismatch-repair Proficient (MSS) Colorectal Cancer

A phase I/II study of PI3Kinase inhibition (copanlisib) and anti-PD-1 antibody nivolumab in relapsed/refractory solid tumors with expansions in mismatch-repair proficient (MSS) colorectal cancer.

NCT03711058 Unresectable or Metastatic Microsatellite Stable (MSS) Solid Tumor Along With Microsatellite Stable (MSS) Colon Cancer Colon Cancer Drug: Copanlisib Drug: Nivolumab

MeSH:Colonic Neoplasms

HPO:Colon cancer Neoplasm of the colon

- Prior therapy with a P13K inhibitor - Chemotherapy, radiotherapy, investigational therapy, or surgery within 4 weeks prior to first dose of treatment. --- P13K ---

38 Phase I/II Clinical Trial of Copanlisib and Ibrutinib in Mantle Cell Lymphoma

The purpose of this study is to test the safety and any good and bad side effects of combining 2 study drugs, copanlisib and ibrutinib. This combination of drugs could shrink your Mantle Cell Lymphoma (MCL), but it could also cause side effects. Both these drugs have been given to people before, but this is the first time that they are being given together.

NCT03877055 Mantle Cell Lymphoma (MCL) Drug: Copanlisib Drug: Ibrutinib

MeSH:Lymphoma Lymphoma, Mantle-Cell

HPO:Lymphoma

Inclusion Criteria: - Patient is ≥ 18 years of age at the time of signing Informed Consent - Patient is able and willing to adhere to the study visit schedule and other protocol requirements - Patient has histologically confirmed diagnosis of R/R mantle cell lymphoma who has received at least 1 line of therapy °Autologous stem cell transplant recipients must have adequate bone marrow recovery and transfusion independent - Patients may have been previously treated with BTK or PI3K inhibitors: °If BTK/P13K inhibitors were part of their last treatment, patients must have had a best response of stable disease or better - Patient has at least one measurable lesion (≥ 2 cm) according to RECIL criteria[37] - Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 - Patient has adequate bone marrow and organ function by: - Absolute neutrophil count (ANC) ≥ 1 x 10^9/L , independent of growth factor support for 14 days unless there is bone marrow involvement. --- P13K ---

- Lipase ≤ 1.5x ULN - LVEF ≥ 50% - Hemoglobin A1c ≤ 8.5% Exclusion Criteria: - Patient has a history of non-compliance to medical regimen or inability to grant consent - Patient is concurrently using other approved or investigational antineoplastic agent with the exception of BTK or Pi3K inhibitors in patients who had these agents as the last line of treatment °Patient on BTK or P13K inhibitors will be continued on therapy as they transition to protocol therapy - Patient has not recovered to Grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy - Patient has had major surgery or a wound that has not fully healed within 4 weeks of starting study drugs. --- P13K ---

39 A Pilot and Feasibility Neoadjuvant Study of a 2-Week Ketogenic Diet in Combination With Letrozole to Modulate PI3K Signaling in ER+ Breast Cancer

This is a neoadjuvant study to determine the feasibility and tolerability of 2 weeks of a very low carbohydrate ketogenic diet in combination with letrozole for patients with early stage operable ER+disease.

NCT03962647 Estrogen Receptor-positive Breast Cancer Dietary Supplement: 2-Week Ketogenic Diet Drug: Letrozole

MeSH:Breast Neoplasms

HPO:Breast carcinoma Neoplasm of the breast

Reduction in measures of insulin/P13K pathway activation. --- P13K ---

40 Window of Opportunity Study of Parsaclisib in Subjects With Newly Diagnosed Stage I-IIIC Triple-Negative or HER2-Positive Breast Cancer

The purpose of this research study is to find the lowest dose of the cancer drug parsaclisib that has an effect on the type of breast cancer a participant has. Researchers are looking at how Parsaclisib affects the immune system. They want to learn whether and how it helps the immune system to find cancer cells to fight them. Parsaclisib is an oral drug that limits the effects of a protein called phosphatidylinositol 3-kinase δ (PI3K). By limiting P13K, parsaclisib can block certain cells that prevent the immune cells from working. As a result, it may help the body's immune system to fight tumors. Parsaclisib is being studied in several clinical trials to treat different types of cancers. Parsaclisib has not yet been approved by FDA for the treatment of cancer. Studies have shown that a good way to find out how cancer acts when exposed to anti-cancer drugs is through a pre-operative window study. In this type of study, tissue and blood are collected before treatment. Then subjects receive a study drug for a few weeks before surgery. Blood is drawn during the course of treatment, and leftover tissue is collected during surgery. Comparing the tissue and blood before and after treatment shows the effects the study drug may have had on the tumor. Research shows that cancers differ when you look at the DNA and RNA (genetic codes) that are inside a cancer cell. DNA and RNA carry genetic information that can determine traits in humans (such as eye color, height, reaction to treatment, etc.), as well as the traits of cancer cells. Depending on the genetic profile (particularly DNA and RNA) of the cancer, it may respond differently to parsaclisib. In this study, the investigators will look at the genetic profile of a participant's tumor by studying tissue and blood samples collected before and after receiving treatment.

NCT04142554 Breast Cancer Breast Neoplasms Triple Negative Breast Cancer HER2-positive Breast Cancer Drug: Parsaclisib

MeSH:Breast Neoplasms Triple Negative Breast Neoplasms

HPO:Breast carcinoma Neoplasm of the breast

By limiting P13K, parsaclisib can block certain cells that prevent the immune cells from working. --- P13K ---

HPO Nodes