SNPMiner Trials by Shray Alag


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Report for Mutation H1047R

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 6 clinical trials

Clinical Trials


1 A Phase II Trial of Endocrine Therapy in Combination With OSI-906 (an IGF-1R Inhibitor) With or Without Erlotinib (Tarceva, an EGFR Inhibitor) in Patients With Hormone-sensitive Metastatic Breast Cancer.

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole +/- goserelin (the latter for pre-menopausal women only) may fight breast cancer by lowering the amount of estrogen the body makes. OSI-906 and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether hormone therapy and OSI-906 are more effective when given with or without erlotinib hydrochloride in treating hormone-sensitive metastatic breast cancer. PURPOSE: This phase II trial is studying how well giving hormone therapy together with OSI-906 with or without erlotinib hydrochloride works in treating hormone-sensitive patients with metastatic breast cancer.

NCT01013506 Breast Cancer Drug: IGF-1R inhibitor OSI-906 Drug: erlotinib hydrochloride Drug: goserelin Drug: letrozole
MeSH:Breast Neoplasms
HPO:Breast carcinoma Neoplasm of the breast

Mutation analysis of PI3K (E542K, E545K, H1047R). --- E542K --- --- E545K --- --- H1047R ---

- To correlate the mutational status of PI3K (E542K, E545K, H1047R) in DNA extracted from FFPB or fresh biopsy with clinical outcome and luminal A vs. luminal B subtypes of breast cancer OUTLINE: This is a multicenter study. --- E542K --- --- E545K --- --- H1047R ---

Primary Outcomes

Description: Duration from study enrollment to date of progressive disease (PD) as measured by Response Evaluation in Solid Tumors (RECIST) criteria v. 1.1: measurable lesions: PD is > 20% increase in the sum of the longest diameter of target lesions or appearance of new lesions

Measure: Time to progression

Time: from study entry to date of progressive disease

Secondary Outcomes

Description: The number of patients with worst-grade toxicity at each of five grades following NCI Common Toxicity Criteria: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, disabling, 5 = death

Measure: Safety profile of OSI-906 and letrozole +/ goserelin, with and without erlotinib

Time: at 4 weeks

Description: Per RECIST criteria v. 1.1: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) > 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) > 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions

Measure: Response

Time: every 12 weeks to progression

Description: Levels of the protein C-peptide and the hormone IGF-1 in the blood

Measure: Circulating C-peptide, IGF-1

Time: At baseline and on day 1 of each 28-day cycle

Description: The levels of these biomarkers will be measured in breast tumor tissue and compared and contrasted with patient's time to progression and molecular classification (luminal A vs. luminal B)

Measure: Correlation of IGF-IR, EGFR, HER2, Y1316 and Y1131 pIGF-1R, PTEN, S473 pAkt, pMAPK, S118 (MAPK site), and S167 (Akt and S6 site) pER expression with time to progression and molecular classification

Time: On receipt of breast tissue: tissue block from prevous surgery or fresh tissue from current surgery

Description: Breast tumor tissue will be examined for mutations in these genes.

Measure: Mutation analysis of PI3K (E542K, E545K, H1047R)

Time: On receipt of breast tissue: tissue block from prevous surgery or fresh tissue from current surgery

2 A Phase Ib/II Study of Cisplatin, Paclitaxel, and RAD001 in Patients With Metastatic Breast Cancer

RATIONALE: Drugs used in chemotherapy, such as cisplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving cisplatin and paclitaxel together with everolimus may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects of giving cisplatin and paclitaxel together with everolimus and to see how well it works in treating patients with metastatic breast cancer.

NCT01031446 Breast Cancer Drug: cisplatin Drug: everolimus Drug: paclitaxel Other: laboratory biomarker analysis
MeSH:Breast Neoplasms
HPO:Breast carcinoma Neoplasm of the breast

- To screen for exon 9 (E542K and E545K), exon 20 (H1047R), and phosphatidylinositol 3-kinase (PI3K) (p110α) mutations in DNA extracted from paraffin blocks. --- E542K --- --- E545K --- --- H1047R ---

Primary Outcomes

Description: The recommended dose for the Phase II trial will be the most prevalent dose delivered per week in Phase I that allows for safe and feasible administration of the medications.The maximum tolerated dose (MTD) is defined as the dose preceding that at which 2 or more of 3 patients experience dose-limiting toxicity (DLT) during the initial cycle of therapy. DLTs include Common Toxicity Criteria (CTC) Grade 4 neutropenia (absolute neutrophil count [ANC] < 0.5 x 10 9/L for > 5 days), febrile neutropenia (ANC < 1.0 x 10 0/L with fever > 38.5 degrees Centigrade) or documented infection associated with Grade 3-4 neutropenia, CTC Grade 4 thrombocytopenia < 25 x 10 9/L or CTC Grade 3 < 50-25 x 10 9/L thrombocytopenia with bleeding, and Grade 3-4 non-hematologic toxicity despite symptomatic therapy.

Measure: Maximum Feasible Dose in Milligrams Per Meter Squared of Body Surface Area (mg/m2) of Cisplatin and Paclitaxel for Women With Metastatic Breast Cancer

Time: at 8 weeks

Description: The recommended dose for the Phase II trial will be the most prevalent dose delivered per day in Phase I that allows for safe and feasible administration the medication. The MTD is defined as the dose preceding that at which 2 or more of 3 patients experience dose-limiting toxicity (DLT) during the initial cycle of therapy. DLTs include Common Toxicity Criteria (CTC) Grade 4 neutropenia (absolute neutrophil count [ANC] < 0.5 x 10 9/L for > 5 days), febrile neutropenia (ANC < 1.0 x 10 0/L with fever > 38.5 degrees Centigrade) or documented infection associated with Grade 3-4 neutropenia, CTC Grade 4 thrombocytopenia < 25 x 10 9/L or CTC Grade 3 < 50-25 x 10 9/L thrombocytopenia with bleeding, and Grade 3-4 non-hematologic toxicity despite symptomatic therapy

Measure: Maximum Feasible Dose in mg of RAD001 (Everolimus)for Women With Metastatic Breast Cancer

Time: at 8 weeks

Description: Patients who had not experienced disease progression and who were alive at 6 months after study entry

Measure: Patients With Progression-free Survival

Time: at 6 months

Secondary Outcomes

Description: Per Response Evaluation Criteria in Solid Tumor (RECIST) criteria v. 1.0: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) > 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) > 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions

Measure: Patients With Overall Response

Time: every 12 weeks

Description: Duration in months from date on-study to date patient exhibited progressive disease

Measure: Time to Progression

Time: Up to 64 weeks

Description: Median duration in months from on-study to disease progression in patients with metastatic basal-like breast cancer. All patients with basal-like breast cancer are negative for estrogen, progesterone, and human epidermal growth factor (HER2) receptors.

Measure: Time to Progression in Patients With Metastatic Basal-like Breast Cancer.

Time: Up to 64 weeks

3 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

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. --- E542K --- --- E545K --- --- H1047R ---

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 --- --- E542K --- --- E545K --- --- H1047R ---

Primary Outcomes

Description: Objective Response Rate (CR or PR) by RECIST 1.1 criteria

Measure: Response Rate

Time: 2 years

Secondary Outcomes

Description: Clinical Benefit Rate (CR, PR, or SD) by RECIST 1.1 criteria

Measure: Clinical Benefit Rate

Time: 2 years

Description: Progression Free Survival (PFS)

Measure: Survival

Time: 2 years

Description: Determine if the presence of specific co-existing mutations may influence clinical benefit from BKM120

Measure: Clinical Benefit

Time: 2 years

4 Study to Evaluate the Safety and Efficacy of Sirolimus, in Subject With Refractory Solid Tumors

This study is a single arm, pilot study of sirolimus in patient with Phosphatidylinositide-3-kinase (PIK3CA) mutation, PIK3CA amplification , PIK3CA-AKT pathway aberration Refractory solid tumor and/or specific sensitivity to mTOR inhibitors by Avatar scan that has progressed following standard therapy or that has not responded to standard therapy or for which there is no standard therapy. sirolimus 1mg will be administered orally daily. To investigate the efficacy and safety of sirolimus in patient with Refractory solid tumor.

NCT02688881 Refractory Solid Tumors Drug: sirolimus
MeSH:Neoplasms
HPO:Neoplasm

- Patients must be >= 19 years of age - Phosphatidylinositide-3-kinase (PIK3CA) mutation, PIK3CA amplification , PIK3CA-AKT pathway aberration( H1047R, E542K, E545K, PTEN LOSS) Refractory solid tumor and/or specific sensitivity to mTOR inhibitors by Avatar scan that has progressed following standard therapy or that has not responded to standard therapy or for which there is no standard therapy. --- H1047R ---

Primary Outcomes

Measure: Progression Free survival

Time: 6 Weeks

Secondary Outcomes

Measure: Overall Response Rate

Time: 24 months

Measure: Time to progression

Time: 24 months

Measure: Overall survival

Time: 24 months

Measure: Number of subjects with Adverse Events as a measure of safety

Time: 24 months

5 A Phase II Evaluation of Copanlisib (BAY 80-6946), a Selective Inhibitor of PI3KCA, in Patients With Persistent or Recurrent Endometrial Carcinoma Harboring PIK3CA Hotspot Mutations

This phase II trial studies how well copanlisib works in treating patients with endometrial cancer that has not decreased or disappeared, and the cancer may still be in the body despite treatment (persistent) or has come back (recurrent). Copanlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

NCT02728258 Endometrial Endometrioid Adenocarcinoma Endometrial Mixed Cell Adenocarcinoma Endometrial Serous Adenocarcinoma Endometrial Undifferentiated Carcinoma Metastatic Endometrioid Adenocarcinoma Recurrent Uterine Corpus Carcinoma Drug: Copanlisib Other: Laboratory Biomarker Analysis
MeSH:Carcinoma Adenocarcinoma Cystadenocarcinoma, Serous Carcinoma, Endometrioid
HPO:Carcinoma

Associations between mutation subtypes and clinical outcomes will be explored using standard statistical methods for categorical and time to event data.. Inclusion Criteria: - Patients must have the psychological ability and general health that permits completion of the study requirements and required follow-up - Women of child-bearing potential (WOCBP) must agree to use adequate contraception when sexually active; patients should continue contraception for 6 months after finishing study drug - Submission of tumor tissue is required for all patients; investigators should check with their site pathology department regarding release of biospecimens before approaching patients about participation in the trial - Patients must have recurrent or persistent endometrial cancer (endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, mixed epithelial carcinoma or adenocarcinoma not otherwise specified [NOS]); histologic confirmation of the primary tumor is required - All patients must have a somatic PIK3CA gene mutation (i.e., R88Q in exon 1, N345K in exon 4, C420R in exon 7, E542K, E545X [E545A, E545D, E545G, and E545K], Q546X [Q546E, Q546K, Q546L, and Q546R] in exon 9, and M1043I, H1047X [H1047L, H1047R, and H1047Y], or G1049R in exon 20) in a representative primary or metastatic tumor sample confirmed by the Roche COBAS PIK3CA Mutation Test at Q^2 Solutions - All patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI - Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as 'non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy - Patients must have recovered from effects of recent surgery, radiotherapy, or chemotherapy; at least 4 weeks must have elapsed since the patient underwent any major surgery (e.g., major: laparotomy, laparoscopy); there is no delay required for minor procedures (e.g., tumor fine-needle aspiration [FNA] or core biopsy, venous access device placement) - Patients may have received prior radiation therapy for treatment of endometrial cancer; prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, intravaginal brachytherapy and/or palliative radiation therapy; all radiation therapy must be completed at least 4 weeks prior to registration - Patients may have received prior hormonal therapy for treatment of endometrial carcinoma; all hormonal therapy must be discontinued at least 4 weeks prior to registration - Patients may have received prior therapy (including chemotherapy, biologic/targeted therapy and immunotherapy) for treatment of endometrial cancer; all therapy must be discontinued at least 4 weeks prior to registration; any investigational agent must be discontinued at least 30 days prior to registration - Patients must have had at least one prior chemotherapeutic regimen for management of endometrial carcinoma; initial treatment may include chemotherapy, chemotherapy and radiation therapy, or consolidation/maintenance therapy; chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen - Patients are allowed to receive, but not required to receive, up to a total of 3 lines of chemotherapy - Appropriate stage for study entry based on the following diagnostic workup: - History/physical examination within 28 days prior to registration - Imaging of target lesion(s) within 28 days prior to registration - Completion of pre-study protocol specific assessments as required - Performance status (Eastern Cooperative Oncology Group [ECOG]/Karnofsky) of 0, 1 or 2 within 28 days prior to registration - Absolute neutrophil count (ANC) >= 1,500/mcl - Platelets >= 75,000/mcl - Hemoglobin (Hgb) >= 8 g/dL - Creatinine =< 1.5 x upper limit of normal (ULN) - Bilirubin =< 1.5 x ULN (=< 3 x ULN for patients with Gilbert syndrome) - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN - Left ventricular ejection fraction (LVEF) >= 50% - Fasting cholesterol less than or equal to 300 mg/dl; fasting triglycerides less than or equal to 300 mg/dl - Prothrombin time (PT) such that international normalized ratio (INR) is less than or equal to 1.5 x ULN (or an in range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a partial thromboplastin time (PTT) less than or equal to 1.5 times the upper limit of normal - The patient must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information - Diabetic patients (type I or II diabetes mellitus) must have baseline hemoglobin (Hb)A1c levels NOT higher than 8.5% at study entry - Patients with hypertension on medical management must have systolic blood pressure < 150 mmHG or diastolic pressure < 90 mmHG at study entry - Note: ULN is institutional or laboratory upper limit of normal - Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test within 28 days of registration; the patient and her sexual partner(s) must agree to use adequate contraception when sexually active for the duration of the study and for 6 months after finishing study drug; a woman is considered of childbearing potential following menarche and until becoming post-menopausal unless permanently sterile; permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy; a postmenopausal state is defined as no menses for 12 months without an alternative medical cause; a high follicle stimulating hormone (FSH) level in the postmenopausal range maybe used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy Exclusion Criteria: - Patients who have had prior therapy with any phosphatidylinositol 3 kinase (PI3K)/v-akt murine thymoma viral oncogene homolog 1 (AKT)/mammalian target of rapamycin (mTor) pathway inhibitor - Patients who have the following histologies: mucinous, squamous, sarcomas, carcinosarcomas, clear cell - Congestive heart failure > New York Heart Association (NYHA) class II - Myocardial infarction or unstable angina less than 6 months before registration - Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before registration - Non-healing wound, ulcer or bone fracture - Active, clinically serious infections > Common Terminology Criteria for Adverse Events (CTCAE) grade 2 - History of, or current autoimmune disease - Human immunodeficiency virus (HIV) infection - Hepatitis B (HBV) or hepatitis C (HCV); all patients must be screened for HBV and HCV up to 28 days prior to study drug start using the routine hepatitis virus laboratorial panel; patients with active HBV or hepatitis C infection are not eligible for enrollment; patients with serologic markers of HBV immunization due to known vaccination (hepatitis B surface antigen [HBsAg] negative, anti-hepatitis B core [HBc] negative and anti-hepatitis B surface [HBs] positive) will be eligible - Previous or concurrent history of malignancies within 5 years prior to study treatment except for curatively treated: - Cervical carcinoma in situ - Non-melanoma skin cancer - Superficial bladder cancer (Ta [non-invasive tumor], Tis [carcinoma in situ] and T1 [tumor invades lamina propria]) - Patients with seizure disorder requiring medication - Patients with evidence or history of bleeding diathesis; any hemorrhage or bleeding event >= CTCAE grade 3 within 4 weeks prior to registration - Proteinuria of CTCAE grade 3 or higher (estimated by urine protein: creatinine ratio >= 3.5 on a random urine sample); patients who recently (i.e., at least 30 days prior to registration) discontinued an anti-angiogenic therapy which caused proteinuria (ie, grade 2 (> 2 to > 3 g of protein or 1-3.5 g/24 hours [h]) or grade 3 proteinuria (> 4 of protein or > 3.5 g/24 h) are not eligible for enrollment until proteinuria improves to < 2 g of protein per 24 h - History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function (as judged by the investigator) - Concurrent diagnosis of pheochromocytoma - Unresolved toxicity higher than CTCAE grade 1 attributed to any prior therapy/procedure, excluding alopecia - Known hypersensitivity to any of the test drugs, test drug classes, or excipients in the formulation - Strong CYP3A4 inhibitors and inducers; concomitant use of strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir and saquinavir), and inducers of CYP3A4 (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, St. John's Wort) are not permitted within two weeks prior to start of study treatment and for the duration of treatment with copanlisib - Grapefruit and grapefruit juice (CYP3A4 inhibitor), Seville oranges and star fruit consumption is not permitted during the study - Anti-arrhythmic therapy other than beta blockers or digoxin - Systemic continuous corticosteroid therapy at a daily dose higher than 15 mg prednisone or equivalent is not allowed; patients may be using topical or inhaled corticosteroids - Concomitant therapy with any anticancer agents, immunosuppressive agents, other investigational anticancer therapies - Concomitant radiotherapy - Women who are breast feeding Inclusion Criteria: - Patients must have the psychological ability and general health that permits completion of the study requirements and required follow-up - Women of child-bearing potential (WOCBP) must agree to use adequate contraception when sexually active; patients should continue contraception for 6 months after finishing study drug - Submission of tumor tissue is required for all patients; investigators should check with their site pathology department regarding release of biospecimens before approaching patients about participation in the trial - Patients must have recurrent or persistent endometrial cancer (endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, mixed epithelial carcinoma or adenocarcinoma not otherwise specified [NOS]); histologic confirmation of the primary tumor is required - All patients must have a somatic PIK3CA gene mutation (i.e., R88Q in exon 1, N345K in exon 4, C420R in exon 7, E542K, E545X [E545A, E545D, E545G, and E545K], Q546X [Q546E, Q546K, Q546L, and Q546R] in exon 9, and M1043I, H1047X [H1047L, H1047R, and H1047Y], or G1049R in exon 20) in a representative primary or metastatic tumor sample confirmed by the Roche COBAS PIK3CA Mutation Test at Q^2 Solutions - All patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI - Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as 'non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy - Patients must have recovered from effects of recent surgery, radiotherapy, or chemotherapy; at least 4 weeks must have elapsed since the patient underwent any major surgery (e.g., major: laparotomy, laparoscopy); there is no delay required for minor procedures (e.g., tumor fine-needle aspiration [FNA] or core biopsy, venous access device placement) - Patients may have received prior radiation therapy for treatment of endometrial cancer; prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, intravaginal brachytherapy and/or palliative radiation therapy; all radiation therapy must be completed at least 4 weeks prior to registration - Patients may have received prior hormonal therapy for treatment of endometrial carcinoma; all hormonal therapy must be discontinued at least 4 weeks prior to registration - Patients may have received prior therapy (including chemotherapy, biologic/targeted therapy and immunotherapy) for treatment of endometrial cancer; all therapy must be discontinued at least 4 weeks prior to registration; any investigational agent must be discontinued at least 30 days prior to registration - Patients must have had at least one prior chemotherapeutic regimen for management of endometrial carcinoma; initial treatment may include chemotherapy, chemotherapy and radiation therapy, or consolidation/maintenance therapy; chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen - Patients are allowed to receive, but not required to receive, up to a total of 3 lines of chemotherapy - Appropriate stage for study entry based on the following diagnostic workup: - History/physical examination within 28 days prior to registration - Imaging of target lesion(s) within 28 days prior to registration - Completion of pre-study protocol specific assessments as required - Performance status (Eastern Cooperative Oncology Group [ECOG]/Karnofsky) of 0, 1 or 2 within 28 days prior to registration - Absolute neutrophil count (ANC) >= 1,500/mcl - Platelets >= 75,000/mcl - Hemoglobin (Hgb) >= 8 g/dL - Creatinine =< 1.5 x upper limit of normal (ULN) - Bilirubin =< 1.5 x ULN (=< 3 x ULN for patients with Gilbert syndrome) - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN - Left ventricular ejection fraction (LVEF) >= 50% - Fasting cholesterol less than or equal to 300 mg/dl; fasting triglycerides less than or equal to 300 mg/dl - Prothrombin time (PT) such that international normalized ratio (INR) is less than or equal to 1.5 x ULN (or an in range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a partial thromboplastin time (PTT) less than or equal to 1.5 times the upper limit of normal - The patient must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information - Diabetic patients (type I or II diabetes mellitus) must have baseline hemoglobin (Hb)A1c levels NOT higher than 8.5% at study entry - Patients with hypertension on medical management must have systolic blood pressure < 150 mmHG or diastolic pressure < 90 mmHG at study entry - Note: ULN is institutional or laboratory upper limit of normal - Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test within 28 days of registration; the patient and her sexual partner(s) must agree to use adequate contraception when sexually active for the duration of the study and for 6 months after finishing study drug; a woman is considered of childbearing potential following menarche and until becoming post-menopausal unless permanently sterile; permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy; a postmenopausal state is defined as no menses for 12 months without an alternative medical cause; a high follicle stimulating hormone (FSH) level in the postmenopausal range maybe used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy Exclusion Criteria: - Patients who have had prior therapy with any phosphatidylinositol 3 kinase (PI3K)/v-akt murine thymoma viral oncogene homolog 1 (AKT)/mammalian target of rapamycin (mTor) pathway inhibitor - Patients who have the following histologies: mucinous, squamous, sarcomas, carcinosarcomas, clear cell - Congestive heart failure > New York Heart Association (NYHA) class II - Myocardial infarction or unstable angina less than 6 months before registration - Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before registration - Non-healing wound, ulcer or bone fracture - Active, clinically serious infections > Common Terminology Criteria for Adverse Events (CTCAE) grade 2 - History of, or current autoimmune disease - Human immunodeficiency virus (HIV) infection - Hepatitis B (HBV) or hepatitis C (HCV); all patients must be screened for HBV and HCV up to 28 days prior to study drug start using the routine hepatitis virus laboratorial panel; patients with active HBV or hepatitis C infection are not eligible for enrollment; patients with serologic markers of HBV immunization due to known vaccination (hepatitis B surface antigen [HBsAg] negative, anti-hepatitis B core [HBc] negative and anti-hepatitis B surface [HBs] positive) will be eligible - Previous or concurrent history of malignancies within 5 years prior to study treatment except for curatively treated: - Cervical carcinoma in situ - Non-melanoma skin cancer - Superficial bladder cancer (Ta [non-invasive tumor], Tis [carcinoma in situ] and T1 [tumor invades lamina propria]) - Patients with seizure disorder requiring medication - Patients with evidence or history of bleeding diathesis; any hemorrhage or bleeding event >= CTCAE grade 3 within 4 weeks prior to registration - Proteinuria of CTCAE grade 3 or higher (estimated by urine protein: creatinine ratio >= 3.5 on a random urine sample); patients who recently (i.e., at least 30 days prior to registration) discontinued an anti-angiogenic therapy which caused proteinuria (ie, grade 2 (> 2 to > 3 g of protein or 1-3.5 g/24 hours [h]) or grade 3 proteinuria (> 4 of protein or > 3.5 g/24 h) are not eligible for enrollment until proteinuria improves to < 2 g of protein per 24 h - History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function (as judged by the investigator) - Concurrent diagnosis of pheochromocytoma - Unresolved toxicity higher than CTCAE grade 1 attributed to any prior therapy/procedure, excluding alopecia - Known hypersensitivity to any of the test drugs, test drug classes, or excipients in the formulation - Strong CYP3A4 inhibitors and inducers; concomitant use of strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir and saquinavir), and inducers of CYP3A4 (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, St. John's Wort) are not permitted within two weeks prior to start of study treatment and for the duration of treatment with copanlisib - Grapefruit and grapefruit juice (CYP3A4 inhibitor), Seville oranges and star fruit consumption is not permitted during the study - Anti-arrhythmic therapy other than beta blockers or digoxin - Systemic continuous corticosteroid therapy at a daily dose higher than 15 mg prednisone or equivalent is not allowed; patients may be using topical or inhaled corticosteroids - Concomitant therapy with any anticancer agents, immunosuppressive agents, other investigational anticancer therapies - Concomitant radiotherapy - Women who are breast feeding Endometrial Endometrioid Adenocarcinoma Endometrial Mixed Cell Adenocarcinoma Endometrial Serous Adenocarcinoma Endometrial Undifferentiated Carcinoma Metastatic Endometrioid Adenocarcinoma Recurrent Uterine Corpus Carcinoma Carcinoma Adenocarcinoma Cystadenocarcinoma, Serous Carcinoma, Endometrioid PRIMARY OBJECTIVES: I. To assess the activity of copanlisib (BAY 80-6946) in patients with persistent or recurrent endometrial carcinoma harboring phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PI3KCA) hotspot mutations with the frequency of objective response. --- R88Q --- --- N345K --- --- C420R --- --- E542K --- --- E545A --- --- E545D --- --- E545G --- --- E545K --- --- Q546E --- --- Q546K --- --- Q546L --- --- Q546R --- --- M1043I --- --- H1047L --- --- H1047R ---

Associations between mutation subtypes and clinical outcomes will be explored using standard statistical methods for categorical and time to event data.. Inclusion Criteria: - Patients must have the psychological ability and general health that permits completion of the study requirements and required follow-up - Women of child-bearing potential (WOCBP) must agree to use adequate contraception when sexually active; patients should continue contraception for 6 months after finishing study drug - Submission of tumor tissue is required for all patients; investigators should check with their site pathology department regarding release of biospecimens before approaching patients about participation in the trial - Patients must have recurrent or persistent endometrial cancer (endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, mixed epithelial carcinoma or adenocarcinoma not otherwise specified [NOS]); histologic confirmation of the primary tumor is required - All patients must have a somatic PIK3CA gene mutation (i.e., R88Q in exon 1, N345K in exon 4, C420R in exon 7, E542K, E545X [E545A, E545D, E545G, and E545K], Q546X [Q546E, Q546K, Q546L, and Q546R] in exon 9, and M1043I, H1047X [H1047L, H1047R, and H1047Y], or G1049R in exon 20) in a representative primary or metastatic tumor sample confirmed by the Roche COBAS PIK3CA Mutation Test at Q^2 Solutions - All patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI - Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as 'non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy - Patients must have recovered from effects of recent surgery, radiotherapy, or chemotherapy; at least 4 weeks must have elapsed since the patient underwent any major surgery (e.g., major: laparotomy, laparoscopy); there is no delay required for minor procedures (e.g., tumor fine-needle aspiration [FNA] or core biopsy, venous access device placement) - Patients may have received prior radiation therapy for treatment of endometrial cancer; prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, intravaginal brachytherapy and/or palliative radiation therapy; all radiation therapy must be completed at least 4 weeks prior to registration - Patients may have received prior hormonal therapy for treatment of endometrial carcinoma; all hormonal therapy must be discontinued at least 4 weeks prior to registration - Patients may have received prior therapy (including chemotherapy, biologic/targeted therapy and immunotherapy) for treatment of endometrial cancer; all therapy must be discontinued at least 4 weeks prior to registration; any investigational agent must be discontinued at least 30 days prior to registration - Patients must have had at least one prior chemotherapeutic regimen for management of endometrial carcinoma; initial treatment may include chemotherapy, chemotherapy and radiation therapy, or consolidation/maintenance therapy; chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen - Patients are allowed to receive, but not required to receive, up to a total of 3 lines of chemotherapy - Appropriate stage for study entry based on the following diagnostic workup: - History/physical examination within 28 days prior to registration - Imaging of target lesion(s) within 28 days prior to registration - Completion of pre-study protocol specific assessments as required - Performance status (Eastern Cooperative Oncology Group [ECOG]/Karnofsky) of 0, 1 or 2 within 28 days prior to registration - Absolute neutrophil count (ANC) >= 1,500/mcl - Platelets >= 75,000/mcl - Hemoglobin (Hgb) >= 8 g/dL - Creatinine =< 1.5 x upper limit of normal (ULN) - Bilirubin =< 1.5 x ULN (=< 3 x ULN for patients with Gilbert syndrome) - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN - Left ventricular ejection fraction (LVEF) >= 50% - Fasting cholesterol less than or equal to 300 mg/dl; fasting triglycerides less than or equal to 300 mg/dl - Prothrombin time (PT) such that international normalized ratio (INR) is less than or equal to 1.5 x ULN (or an in range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a partial thromboplastin time (PTT) less than or equal to 1.5 times the upper limit of normal - The patient must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information - Diabetic patients (type I or II diabetes mellitus) must have baseline hemoglobin (Hb)A1c levels NOT higher than 8.5% at study entry - Patients with hypertension on medical management must have systolic blood pressure < 150 mmHG or diastolic pressure < 90 mmHG at study entry - Note: ULN is institutional or laboratory upper limit of normal - Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test within 28 days of registration; the patient and her sexual partner(s) must agree to use adequate contraception when sexually active for the duration of the study and for 6 months after finishing study drug; a woman is considered of childbearing potential following menarche and until becoming post-menopausal unless permanently sterile; permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy; a postmenopausal state is defined as no menses for 12 months without an alternative medical cause; a high follicle stimulating hormone (FSH) level in the postmenopausal range maybe used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy Exclusion Criteria: - Patients who have had prior therapy with any phosphatidylinositol 3 kinase (PI3K)/v-akt murine thymoma viral oncogene homolog 1 (AKT)/mammalian target of rapamycin (mTor) pathway inhibitor - Patients who have the following histologies: mucinous, squamous, sarcomas, carcinosarcomas, clear cell - Congestive heart failure > New York Heart Association (NYHA) class II - Myocardial infarction or unstable angina less than 6 months before registration - Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before registration - Non-healing wound, ulcer or bone fracture - Active, clinically serious infections > Common Terminology Criteria for Adverse Events (CTCAE) grade 2 - History of, or current autoimmune disease - Human immunodeficiency virus (HIV) infection - Hepatitis B (HBV) or hepatitis C (HCV); all patients must be screened for HBV and HCV up to 28 days prior to study drug start using the routine hepatitis virus laboratorial panel; patients with active HBV or hepatitis C infection are not eligible for enrollment; patients with serologic markers of HBV immunization due to known vaccination (hepatitis B surface antigen [HBsAg] negative, anti-hepatitis B core [HBc] negative and anti-hepatitis B surface [HBs] positive) will be eligible - Previous or concurrent history of malignancies within 5 years prior to study treatment except for curatively treated: - Cervical carcinoma in situ - Non-melanoma skin cancer - Superficial bladder cancer (Ta [non-invasive tumor], Tis [carcinoma in situ] and T1 [tumor invades lamina propria]) - Patients with seizure disorder requiring medication - Patients with evidence or history of bleeding diathesis; any hemorrhage or bleeding event >= CTCAE grade 3 within 4 weeks prior to registration - Proteinuria of CTCAE grade 3 or higher (estimated by urine protein: creatinine ratio >= 3.5 on a random urine sample); patients who recently (i.e., at least 30 days prior to registration) discontinued an anti-angiogenic therapy which caused proteinuria (ie, grade 2 (> 2 to > 3 g of protein or 1-3.5 g/24 hours [h]) or grade 3 proteinuria (> 4 of protein or > 3.5 g/24 h) are not eligible for enrollment until proteinuria improves to < 2 g of protein per 24 h - History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function (as judged by the investigator) - Concurrent diagnosis of pheochromocytoma - Unresolved toxicity higher than CTCAE grade 1 attributed to any prior therapy/procedure, excluding alopecia - Known hypersensitivity to any of the test drugs, test drug classes, or excipients in the formulation - Strong CYP3A4 inhibitors and inducers; concomitant use of strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir and saquinavir), and inducers of CYP3A4 (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, St. John's Wort) are not permitted within two weeks prior to start of study treatment and for the duration of treatment with copanlisib - Grapefruit and grapefruit juice (CYP3A4 inhibitor), Seville oranges and star fruit consumption is not permitted during the study - Anti-arrhythmic therapy other than beta blockers or digoxin - Systemic continuous corticosteroid therapy at a daily dose higher than 15 mg prednisone or equivalent is not allowed; patients may be using topical or inhaled corticosteroids - Concomitant therapy with any anticancer agents, immunosuppressive agents, other investigational anticancer therapies - Concomitant radiotherapy - Women who are breast feeding Inclusion Criteria: - Patients must have the psychological ability and general health that permits completion of the study requirements and required follow-up - Women of child-bearing potential (WOCBP) must agree to use adequate contraception when sexually active; patients should continue contraception for 6 months after finishing study drug - Submission of tumor tissue is required for all patients; investigators should check with their site pathology department regarding release of biospecimens before approaching patients about participation in the trial - Patients must have recurrent or persistent endometrial cancer (endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, mixed epithelial carcinoma or adenocarcinoma not otherwise specified [NOS]); histologic confirmation of the primary tumor is required - All patients must have a somatic PIK3CA gene mutation (i.e., R88Q in exon 1, N345K in exon 4, C420R in exon 7, E542K, E545X [E545A, E545D, E545G, and E545K], Q546X [Q546E, Q546K, Q546L, and Q546R] in exon 9, and M1043I, H1047X [H1047L, H1047R, and H1047Y], or G1049R in exon 20) in a representative primary or metastatic tumor sample confirmed by the Roche COBAS PIK3CA Mutation Test at Q^2 Solutions - All patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI - Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as 'non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy - Patients must have recovered from effects of recent surgery, radiotherapy, or chemotherapy; at least 4 weeks must have elapsed since the patient underwent any major surgery (e.g., major: laparotomy, laparoscopy); there is no delay required for minor procedures (e.g., tumor fine-needle aspiration [FNA] or core biopsy, venous access device placement) - Patients may have received prior radiation therapy for treatment of endometrial cancer; prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, intravaginal brachytherapy and/or palliative radiation therapy; all radiation therapy must be completed at least 4 weeks prior to registration - Patients may have received prior hormonal therapy for treatment of endometrial carcinoma; all hormonal therapy must be discontinued at least 4 weeks prior to registration - Patients may have received prior therapy (including chemotherapy, biologic/targeted therapy and immunotherapy) for treatment of endometrial cancer; all therapy must be discontinued at least 4 weeks prior to registration; any investigational agent must be discontinued at least 30 days prior to registration - Patients must have had at least one prior chemotherapeutic regimen for management of endometrial carcinoma; initial treatment may include chemotherapy, chemotherapy and radiation therapy, or consolidation/maintenance therapy; chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen - Patients are allowed to receive, but not required to receive, up to a total of 3 lines of chemotherapy - Appropriate stage for study entry based on the following diagnostic workup: - History/physical examination within 28 days prior to registration - Imaging of target lesion(s) within 28 days prior to registration - Completion of pre-study protocol specific assessments as required - Performance status (Eastern Cooperative Oncology Group [ECOG]/Karnofsky) of 0, 1 or 2 within 28 days prior to registration - Absolute neutrophil count (ANC) >= 1,500/mcl - Platelets >= 75,000/mcl - Hemoglobin (Hgb) >= 8 g/dL - Creatinine =< 1.5 x upper limit of normal (ULN) - Bilirubin =< 1.5 x ULN (=< 3 x ULN for patients with Gilbert syndrome) - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN - Left ventricular ejection fraction (LVEF) >= 50% - Fasting cholesterol less than or equal to 300 mg/dl; fasting triglycerides less than or equal to 300 mg/dl - Prothrombin time (PT) such that international normalized ratio (INR) is less than or equal to 1.5 x ULN (or an in range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a partial thromboplastin time (PTT) less than or equal to 1.5 times the upper limit of normal - The patient must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information - Diabetic patients (type I or II diabetes mellitus) must have baseline hemoglobin (Hb)A1c levels NOT higher than 8.5% at study entry - Patients with hypertension on medical management must have systolic blood pressure < 150 mmHG or diastolic pressure < 90 mmHG at study entry - Note: ULN is institutional or laboratory upper limit of normal - Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test within 28 days of registration; the patient and her sexual partner(s) must agree to use adequate contraception when sexually active for the duration of the study and for 6 months after finishing study drug; a woman is considered of childbearing potential following menarche and until becoming post-menopausal unless permanently sterile; permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy; a postmenopausal state is defined as no menses for 12 months without an alternative medical cause; a high follicle stimulating hormone (FSH) level in the postmenopausal range maybe used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy Exclusion Criteria: - Patients who have had prior therapy with any phosphatidylinositol 3 kinase (PI3K)/v-akt murine thymoma viral oncogene homolog 1 (AKT)/mammalian target of rapamycin (mTor) pathway inhibitor - Patients who have the following histologies: mucinous, squamous, sarcomas, carcinosarcomas, clear cell - Congestive heart failure > New York Heart Association (NYHA) class II - Myocardial infarction or unstable angina less than 6 months before registration - Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before registration - Non-healing wound, ulcer or bone fracture - Active, clinically serious infections > Common Terminology Criteria for Adverse Events (CTCAE) grade 2 - History of, or current autoimmune disease - Human immunodeficiency virus (HIV) infection - Hepatitis B (HBV) or hepatitis C (HCV); all patients must be screened for HBV and HCV up to 28 days prior to study drug start using the routine hepatitis virus laboratorial panel; patients with active HBV or hepatitis C infection are not eligible for enrollment; patients with serologic markers of HBV immunization due to known vaccination (hepatitis B surface antigen [HBsAg] negative, anti-hepatitis B core [HBc] negative and anti-hepatitis B surface [HBs] positive) will be eligible - Previous or concurrent history of malignancies within 5 years prior to study treatment except for curatively treated: - Cervical carcinoma in situ - Non-melanoma skin cancer - Superficial bladder cancer (Ta [non-invasive tumor], Tis [carcinoma in situ] and T1 [tumor invades lamina propria]) - Patients with seizure disorder requiring medication - Patients with evidence or history of bleeding diathesis; any hemorrhage or bleeding event >= CTCAE grade 3 within 4 weeks prior to registration - Proteinuria of CTCAE grade 3 or higher (estimated by urine protein: creatinine ratio >= 3.5 on a random urine sample); patients who recently (i.e., at least 30 days prior to registration) discontinued an anti-angiogenic therapy which caused proteinuria (ie, grade 2 (> 2 to > 3 g of protein or 1-3.5 g/24 hours [h]) or grade 3 proteinuria (> 4 of protein or > 3.5 g/24 h) are not eligible for enrollment until proteinuria improves to < 2 g of protein per 24 h - History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function (as judged by the investigator) - Concurrent diagnosis of pheochromocytoma - Unresolved toxicity higher than CTCAE grade 1 attributed to any prior therapy/procedure, excluding alopecia - Known hypersensitivity to any of the test drugs, test drug classes, or excipients in the formulation - Strong CYP3A4 inhibitors and inducers; concomitant use of strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir and saquinavir), and inducers of CYP3A4 (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, St. John's Wort) are not permitted within two weeks prior to start of study treatment and for the duration of treatment with copanlisib - Grapefruit and grapefruit juice (CYP3A4 inhibitor), Seville oranges and star fruit consumption is not permitted during the study - Anti-arrhythmic therapy other than beta blockers or digoxin - Systemic continuous corticosteroid therapy at a daily dose higher than 15 mg prednisone or equivalent is not allowed; patients may be using topical or inhaled corticosteroids - Concomitant therapy with any anticancer agents, immunosuppressive agents, other investigational anticancer therapies - Concomitant radiotherapy - Women who are breast feeding Endometrial Endometrioid Adenocarcinoma Endometrial Mixed Cell Adenocarcinoma Endometrial Serous Adenocarcinoma Endometrial Undifferentiated Carcinoma Metastatic Endometrioid Adenocarcinoma Recurrent Uterine Corpus Carcinoma Carcinoma Adenocarcinoma Cystadenocarcinoma, Serous Carcinoma, Endometrioid PRIMARY OBJECTIVES: I. To assess the activity of copanlisib (BAY 80-6946) in patients with persistent or recurrent endometrial carcinoma harboring phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PI3KCA) hotspot mutations with the frequency of objective response. --- R88Q --- --- N345K --- --- C420R --- --- E542K --- --- E545A --- --- E545D --- --- E545G --- --- E545K --- --- Q546E --- --- Q546K --- --- Q546L --- --- Q546R --- --- M1043I --- --- H1047L --- --- H1047R --- --- H1047Y --- --- G1049R --- --- R88Q --- --- N345K --- --- C420R --- --- E542K --- --- E545A --- --- E545D --- --- E545G --- --- E545K --- --- Q546E --- --- Q546K --- --- Q546L --- --- Q546R --- --- M1043I --- --- H1047L --- --- H1047R ---

Primary Outcomes

Description: Confirmed complete and partial tumor response by RECIST 1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Measure: Frequency of Objective Response Defined by RECIST 1.1 Criteria

Time: approximate study duration 1 year 9 months

Secondary Outcomes

Description: Percentage of participants who are progression free at 6 months. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Measure: Percentage of Participants Alive and Progression-free at 6 Months

Time: Up to 6 months from enrollment

Description: The median progression-free survival time

Measure: Median Progression-Free Survival Using RECIST 1.1 Criteria

Time: September 16,2016 to April 4,2019, approximate duration of 2 years, 7 months

Description: Median time of overall survival

Measure: Median Overall Survival

Time: September 16,2016 to April 4,2019, approximate duration of 2 years, 7 months

Description: Maximum grade of physician assessed adverse events reported during treatment

Measure: The Frequency and Severity of CTCAE v4 Graded Adverse Events

Time: Study Start: September 16, 2016, Primary Completion: June 30, 2018, approximate study duration 1 year 9 months

Other Outcomes

Description: Associations between mutation subtypes and clinical outcomes will be explored using standard statistical methods for categorical and time to event data.

Measure: Mutation Subtypes and Clinical Outcomes

Time: Up to 5 years

6 INST UNM 1601: Compassionate Use of BYL 719 Alpelisib

This is a compassionate use protocol of BYL719 (alpelisib) treatment for a single patient with locally advanced lymphangioma positive PI3K alpha H1047R mutation.

NCT03941782 Lymphangioma Drug: Alpelisib
MeSH:Lymphangioma
HPO:Lymphangioma

Compassionate Use of BYL 719 Alpelisib This is a compassionate use protocol of BYL719 (alpelisib) treatment for a single patient with locally advanced lymphangioma positive PI3K alpha H1047R mutation. --- H1047R ---



HPO Nodes


HP:0002664: Neoplasm
Genes 1515
EPCAM BAP1 CYLD WT1 CTBP1 GLI3 CTNNB1 ELMO2 ATRX TERT EDN3 MTAP TSC2 RAD51 BLNK KCNAB2 WDPCP SPINK1 ARID1B PTEN STK11 XPA PTH1R TCF4 EPCAM NF1 GPC3 ERCC3 MC1R CASP10 PDGFRA RPL5 CDH1 BRIP1 RUNX1 KRAS SFTPC GPR35 MYLK STS DYNC2LI1 RAG2 CBL FOXE1 STAT3 TTC37 ABL1 NSD1 ATM KCNH1 GPR101 IGH KRT17 SUFU TERT KRAS GPC3 CYP11B2 MLH3 PTCH1 FAH MSH2 EXT1 CCND1 MSH3 ATP7A SEC23A PHOX2B HAX1 MYD88 LMO1 PIK3CA PRLR AXIN1 TCF4 RUNX1 AKT1 ERBB2 REST DCLRE1C SERPINA1 ERCC3 TMC6 RASA1 MSH3 TRNL1 CALR HRAS INS RNF113A SETBP1 CDH1 SLC37A4 TFAP2A CDH1 PTCH1 KIT PTEN IL1RN MLH3 MUTYH PTEN KIT GBA BCL2 KCNH1 GINS1 ESCO2 TET2 SLX4 DICER1 PALB2 NEK1 ESCO2 COL7A1 PTCH2 WT1 WRN GCM2 BRD4 BRAF TREX1 THPO SUFU NRAS CDC73 POU6F2 GNAS DAXX BUB3 RSPO1 MNX1 ERCC2 RPS28 ANTXR2 CTNNB1 POT1 FANCA KDM6B RET MST1 NOTCH3 FGFR1 KRAS LYST CHIC2 TMC6 MET KRT10 UROD SLC25A11 ARSA EVC2 TEK XRCC2 CASP8 ASCL1 IL1B TERF2IP DICER1 MPL OFD1 RHBDF2 DICER1 MDM2 WT1 MMP1 CDKN2A FGF8 NR4A3 FGFR2 OCRL TP53 ERCC2 SUFU ERCC4 ALX4 TINF2 DCLRE1C SRY SRP72 NF2 GNAS LETM1 TP53 FANCB TAL1 TDGF1 BRCA1 LEMD3 NF2 BRAF NUP214 RAD21 COL18A1 SDHD ICOS CEP57 BAP1 FANCM PTPRJ FANCE SLC22A18 PIK3R1 JAK2 FLT4 SMO WIPF1 DLST NF2 RAD50 MEN1 CHEK2 GPC4 WDPCP CYP2A6 HBB GANAB XRCC4 TET2 ATP7B EP300 DIS3L2 HFE CARD14 OFD1 ALX3 VANGL1 BAP1 SDHB EXTL3 PIK3CA GATA2 ALX3 BCL10 KIT WAS FGFR2 RMRP TWIST1 BMPR1B DIS3L2 ERCC3 FOXP1 SMAD4 CALR APC PCGF2 USP8 DMPK NRAS DKC1 BRCA1 ADAR BCR RSPO1 SLC45A2 GJC2 TNFRSF4 AKT1 IFIH1 MSH6 DICER1 PAX6 TGFBR2 SRY KLHDC8B CPLX1 MSH6 AIP PMS1 CREBBP ERCC2 CTSA APC MMP1 SH2B3 PKD1 TRNF SEC23B DNAJC21 STK11 BCR HBB MITF IGLL1 ALX4 MDH2 AKT1 SCN4A SDHAF2 PRKN PLA2G2A RNF43 DNMT3A TERT NSD2 RMRP FANCG BRCA2 CAT TP53 BMPR1A MAD2L2 SIX6 DDB2 GREM1 KRT17 PAX4 RPS17 TRPV3 ERCC4 C11ORF95 APC IL12RB1 BRIP1 PPM1D SDHB NODAL HNF1A FLT4 MSH6 ERCC6 BTK SLC26A4 SEMA3C AR NEK1 TERC RPL35A RPS20 CDKN1C SF3B1 TERC PTEN RFWD3 BRCA2 KCNQ1OT1 RPL10 ACTG2 MAGT1 ALK BLM H19 LEMD3 RPL31 MLLT10 PYGL RPL15 IRF1 CR2 MITF PTEN MYC PTPN11 TUBB TCF4 KCNQ1 NFKB2 ALX1 HLA-DRB1 APC EWSR1 NBN CDKN2A ERCC4 GCK DLL1 SLC25A11 PDGFB L2HGDH PRKCD CTC1 PIK3CA SUFU RPL27 KIF1B SRC CIB1 RECQL4 CDKN2B MSH3 BRCA2 PALB2 PDE6D SDHC SDHD CCL2 CHEK2 PMVK XPC STK11 PIK3CA MVD DHCR7 KIT GPC6 KARS1 MNX1 VHL TUBB NAB2 KEAP1 TSC1 NQO2 APC SDHB VHL TCTN3 RECQL4 PMS2 RAD51C STAG3 SNAI2 MAP3K8 SETBP1 SDHB NPM1 RAD51C RARA ERBB2 ERCC5 ATRX CHEK2 KRAS BRCA1 TFAP2A SLCO2A1 PHOX2B PTEN COL2A1 PIGL PDGFRA APC CPLANE1 AURKA SDHD LAMA3 VHL RPS26 GFI1B CDKN1B PRDM16 AXIN2 FZD2 AP2S1 LZTR1 TP53 TP53 GNA14 CTNNB1 MSTO1 PIK3CA RPS29 CALR DHX37 MYF6 SDHC MALT1 ELANE SDHD SLC26A4 MAP3K1 GDNF MSH2 SDHC TGFBR1 RUNX1 CREB1 CDKN2A TSC2 KRAS TNFRSF10B LMNA WWOX PHOX2B EDN3 RPS10 RSPRY1 TRIM37 RET MEN1 BCL10 MSH2 TNFRSF13C FOXE1 FANCC H19-ICR BLM ERCC6 LIG4 BDNF LMOD1 NF2 TMEM107 CYLD GJB2 EXT1 CTSC PHOX2B RAD51D RASGRP1 RB1 TGFBR2 SRY MYH8 KRAS TINF2 RECQL4 H19 PRF1 GDNF MXI1 SMPD1 WT1 HRAS COL1A1 PDGFRB FAS FANCD2 NF1 DISP1 PDGFRL IKBKG BIN1 BRCA2 ADA POLE AXIN2 SEMA4A KRAS NRAS PALB2 CHEK2 ASCL1 POLE TLR2 PIK3CA MINPP1 SOS1 CYLD CTLA4 POT1 ASXL1 CDC73 APC SAMD9L WT1 TRAF7 GATA4 PIK3CA DYNC2LI1 ATP7A CBFB MST1R GCGR MPL COL4A5 SMAD4 CDKN1A SDHD TRIM28 POLH GPR101 PIK3CA FLCN GPR143 RB1 SBDS SLC12A3 KLF6 ICOS GNB1 PIGA TYROBP GFI1 RAD51 SLC26A2 MC1R TREM2 SFTPA2 JAG1 BAP1 EGFR IGH KIT PLCB4 NLRP1 HNF1B ZFHX3 EPHB2 KLLN OCA2 WT1 FAH FH TERT SRD5A3 LIG4 NFKB1 RNF43 KIT STAT1 IFNG BMPR1A ERCC3 TBX18 TET2 MAP2K1 EXT2 HRAS RTEL1 FGFR3 PTEN CTNNB1 MAP2K2 MEN1 APC CLCNKB AKT1 ESCO2 CDC73 MS4A1 BRAF CRKL NUTM1 CDK4 NTHL1 ETV6 TET2 SQSTM1 FAM20C PIGL SEC23A ATM PALB2 TYR SRSF2 EXT2 GJB2 DNMT3A HRAS TCOF1 CHEK2 CDH1 FH DKC1 POLE PIK3CA PTCH2 AKT1 PAX3 FH ADAMTS3 APC PMS1 RAD51C PLCD1 PUF60 DIS3L2 CDH23 SCN9A FOXC2 SMARCB1 CDKN2A VANGL2 ENG SH2D1A SDHB SOX9 BRAF SDHA PGM3 ERCC2 GJB2 TBC1D24 CHD7 MPL DHH PTCH1 CALR IL12A TNFRSF13B CD28 MLH1 PTPN12 OFD1 MLH3 REST CCDC22 APPL1 COL14A1 IGH PSENEN IL2RG MC1R SMARCA4 CYLD KIF11 PHKG2 JAK2 COL2A1 AXIN2 FLNA WNT5A TYR EP300 GLI3 EXT2 MGAT2 KCNE3 ECE1 PARN IDH2 TSC1 ARL6IP6 FGFR3 SMAD4 HMBS SLC6A17 PRKAR1A BAP1 KDSR DHCR24 CXCR4 DDX41 GABRD RET NR0B1 DMRT3 CCND1 GDF5 POU6F2 CTLA4 TBXT FANCA NRTN PHKA2 KIT ITK RNASEH2A PERP CDC73 OFD1 CYP2D6 RET MEN1 CD27 PARN FUZ RPS19 MSH2 SMARCE1 TNFSF12 ZSWIM6 TERT RHOH NF1 BUB1B SLX4 LIG4 PDGFRL TNFSF15 OPCML APC PRKCD SETD2 RPS19 BRCA1 FAT4 ANTXR1 WNT10A SUFU TP63 EFL1 IL7 MN1 DOCK8 CDC73 SSX1 TMEM231 MPLKIP VHL MINPP1 BIRC3 PDX1 STS PSAP HNF1A JAK2 FANCL POT1 GNAS TERT CD79A KLF11 WRN MAPRE2 LIG4 CYSLTR2 DNM2 SH3GL1 KIT FOXH1 RELA KRAS PRKAR1A ERBB3 FGFR2 H19 TJP2 CD81 PNP MSH6 WT1 THPO ATP6V1B2 GNAQ BRCA1 WRAP53 ERCC3 CHRNG KRT14 TSC1 DLC1 CTNNB1 FGFRL1 SDHC GDNF HABP2 NRAS ATR TRNK BMPR1A TERT BRAF AKT1 XPC FGFR3 NUP214 TRIP13 SMARCD2 ZSWIM6 PIEZO2 EVC IL6 HRAS GPC4 TNFRSF13B PALLD CDKN2A POLR1D TP53 FOXO1 BRCA2 FIBP CDH23 RB1CC1 B3GALT6 FLT3 GJA1 SH2B3 MRAP MTOR AR FOXI1 TP53 GNAQ KRT6B MYD88 KRT16 TP53 NF1 MYSM1 MGMT KIT NF1 GPC4 GCM2 SIX3 PIK3CA RAD21 HRAS PMS2 ASCC1 BRCA2 GAS1 FASLG SDHD NRAS C2CD3 KDR SDHA SMAD4 SOX2 NBEAL2 SRGAP1 AGGF1 ATM AKT1 RPGRIP1L NOD2 BAX BRCA2 H19-ICR TGIF1 MAPK1 ESR1 EXT1 RPL11 KRAS BCL10 SKI LAMB3 XIAP SDHC HABP2 TRNS1 CCM2 FIBP PIK3CA TRIM28 HRAS SCN10A NF1 WT1 CPLANE1 HFE F5 C2CD3 GNPTAB TBX2 KLF6 GATA2 VEGFC RNASEH2B CBL SEMA3D ARMC5 CXCR4 JAK2 IGF2 FGFR2 NRAS UBE2T ARHGAP26 SCN11A MEN1 LMX1B F13A1 BCR COMP EDN1 SDHC ACTB GDNF CDKN2C ASPSCR1 NAGS PDGFRB PALB2 DLEC1 BCL10 STAR GNA11 PORCN RNR1 FLCN SPIB WT1 RET SDHB SLC22A18 ERCC4 CDKN2A CTHRC1 DLST OGG1 POLD1 DCC IL2RG REST SRP54 RAF1 TSC1 SRP54 IDH1 ACD KIT ACAN NSD2 TOP2A CASP10 DVL1 PTPN11 CASP10 STIM1 KRT9 AR CIB1 GNAS AR VAMP7 MRE11 GFI1 RPS14 BCL10 CACNA1S TP53 VANGL1 SKIV2L PTCH2 G6PC LRP5 PDGFRB BARD1 RPS27 RPS7 GNAS ENPP1 STAT6 ACVR1 MTM1 NEUROD1 TNFRSF13C PKD2 RUNX1 STK11 FGF3 TRIP13 SIX1 BRCA2 LAMC2 NELFA DVL3 GJB4 NSUN2 CDKN1B CTNNB1 POLR1C GJB3 SMARCB1 SBDS LMNA KRAS TRNH ECM1 STK4 ANTXR2 SOS1 BAP1 MSX2 DICER1 SDHB ACD WRAP53 BRCA1 ATP7A BUB1B RYR1 RET BRCA2 TP53 DPM1 BRCA2 BCR POLD1 TCIRG1 PTPN11 HOXD13 CR2 TARS1 JAK2 BMP2 MUTYH FLT3 TRNS2 MTMR14 NR5A1 ABCA5 RET AHCY TSC2 KIT KCNQ1OT1 RNF6 RAD54L HNF1A HMMR RNF139 WWOX TCTN3 BRAF FCN3 RNASEH2C AIP PRKN SF3B1 MSH6 NSD1 PTCH2 CCBE1 RECQL4 PMS2 ERCC2 HNF4A MMEL1 BUB1 TET2 TRPS1 ABCC6 RET IRF5 CDKN2B PDGFB USP9X TAL2 INTU GNAS HDAC4 MFN2 DYNC2H1 PIK3CA PLAG1 ATM MAX FAS PIK3CA CYP11B1 CCND1 H19-ICR PTCH1 MUTYH ABL1 ODC1 FGFR2 COL7A1 MSR1 BRCA1 RB1 TNFRSF1B COL7A1 FLT4 GPC3 TGFBR2 ATRX RAG1 PRCC BRAF TNFRSF1B FANCE RAD54L CBL SDHB TERT SDHD RPS24 FASLG MET KRT17 GATA1 ERBB2 FGFR1 KAT6B ABCA5 SDHAF2 SLC25A13 NOP10 GATA2 RFWD3 PDGFRA SPRTN MLH1 NKX2-1 IGF2R CD19 MAP3K1 TREX1 TRNP ZFPM2 CTNNB1 TRNQ WWOX IGHM MYH11 TMEM127 CDON NF2 SAMD9 PTEN RNASEL IDH2 HNF4A GTF2H5 GLI3 HRAS LPP DDB2 KIT PIK3CA PDCD10 HSPG2 HFE RPL26 BRIP1 ASXL1 SDHD CEBPA ACVRL1 NRAS CD19 GNAQ TET2 TCTN3 SMARCB1 FLCN ABCB11 BLK RAD54B SDHC FH AKT1 ANTXR1 FANCF HNF1B EXOC6B SAMHD1 SHOX MYO1H COL11A2 KCNJ10 TRIP13 CC2D2A LZTS1 SEC23B GPR101 DOCK8 BRCA2 NBN SLC26A2 SPRED1 VHL KRT1 LIN28B GTF2E2 NRAS ZIC2 SNAI2 SH3KBP1 SHOX BCL6 NTHL1 RHBDF2 CD28 MCM4 CCND1 FANCG SMARCAD1 GATA2 RERE YY1 ASXL1 IL7R TMEM67 C1S TAF1 FGFR3 NBN KRAS KIF1B AIP KCNJ11 LETM1 FANCI MLH1 MBTPS2 NRAS NEK9 GNAI3 APC2 EYA1 ZAP70 EXT2 BUB1 SSX2 LIG4 CARMIL2 SLC17A9 TMC8 PCNA EPAS1 TFE3 BRCA2 DHH MAP2K1 CASP8 CDK4 PDGFB RTEL1 EWSR1 PTEN VHL GJB6 NDP RNF6 TNPO3 TGFBR2 TXNRD2 PNP TAF15 TRNK SMO NOTCH1 LRRC8A RASA1 TSC2 ABCC8 PRKAR1A BAX IDH1 SLC22A18 ADA FAN1 TG PTEN BMPR1A MSTO1 ERCC5 IRF1 MLH1 NRAS MLH1 PICALM FANCD2 SF3B1 BICC1 RPS15A TERT KLLN ELANE FAM149B1 GATA1 SASH1 INPP5E TP53 WT1 BMPR1A PTPN11 PTPN11 MYCN XPA EDNRB TP53 FLI1 GDF2 PHB BMPER FGFR3 PTEN MCC EXT1 MC2R KCNN3 DNASE1L3 DHCR7 RASGRP1 SHH NPM1 SLC26A2 SLC37A4 IGF2 RPL18 SH2B3 PTCH1 BRAF PAX7 INHBA BMPR1A KIF7 XRCC3 IGF2 POU2AF1 DNAJC21 CYP26C1 RB1 MPL REST KIAA0753 DNMT3A ERCC6 MUC5B MLH3 ASXL1 MPL NOTCH3 KCNJ10 SMARCE1 TSR2 RPL10 KRT1 SLC25A13 WT1 NNT TP53 GNA11 GLI1 BARD1 FLCN COL7A1 SRP54 GLI2 EDN3 PTPN3 WT1 TMEM127 CD79B GATA2 TERC FN1 EIF2AK4 RAD51 WASHC5 SAMD9L AIP TP53 AAGAB RB1 TP53 KRT5 ADA2 HSPA9 PIK3CA SRSF2 PHF21A IDH1 KRAS KRAS CHEK2 BUB1B RET FANCC TP53 WHCR RAD54B NUMA1 SDHB HMBS TMEM216 SMAD4 MAFA MSH2 RPL35 CDKN1B IGF2 PPP2R1B CD70 CEL MAD1L1 MAX ALK GPC3 FERMT1 KIF1B TCF3 POLH PIK3R1 USF3 FDPS MYC DNAJC21 TNFSF12 HACE1 CDH1 SDHA ND5 NHP2 PIK3CA RPS14 NBN WNT10A ING1 CASR SUFU FGFR3 HPGD BTK ENG DCC CASP8 PHOX2B STAC3 USB1 KRIT1 PHOX2B TET2 SMAD4 JAK2 BCHE APC MVK SMAD7 SMO DKC1 SMARCB1 VHL F13B TINF2 USP8 FGFR1 FOXI1 TET2 CD96 TET2 JAK2 KRAS