This study is a Phase I, open label, multi-center study of to evaluate the safety and efficacy of JMT101 in patients with advanced solid tumor.

NCT04689100

Conditions

1. Advanced Solid Tumor

Interventions

1. Drug: JMT101
2. Drug: JMT101

MeSH:Neoplasms

HPO:Neoplasm

The content of RAS(reticular activating system), EGFR(epidermal growth factor receptor), BRAF(B-Raf proto-oncogene) gene will be detected.. Inclusion Criteria: - Monotherapy: Pathologically or cytologically confirmed, advanced solid tumor, harboring RAS wild type; Combined with chemotherapy: Pathologically or cytologically confirmed, locally advanced /metastatic colorectal cancer, harboring RAS and BRAF V600E wild type. --- V600E ---

- Receiving an investigational product in another clinical study within 4 weeks; - History of serious systemic diseases; - Pregnancy or lactating wo Inclusion Criteria: - Monotherapy: Pathologically or cytologically confirmed, advanced solid tumor, harboring RAS wild type; Combined with chemotherapy: Pathologically or cytologically confirmed, locally advanced /metastatic colorectal cancer, harboring RAS and BRAF V600E wild type. --- V600E ---

A Phase 1a/1b Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PY159 as a Single Agent and In Combination with Pembrolizumab in Subjects with Advanced Solid Tumors

NCT04682431

Conditions

1. Advanced Solid Tumor

Interventions

1. Drug: PY159 Single agent dose level 1
2. Drug: PY159 Single agent dose level 2
3. Drug: PY159 Single agent dose level 3
4. Drug: PY159 Single agent dose level 4
5. Drug: PY159 Single agent dose level 5
6. Drug: PY159 Single agent dose level 6
7. Drug: PY159 Single agent dose level 7
8. Drug: PY159/Pembrolizumab Combination dose level 1
9. Drug: PY159/Pembrolizumab Combination dose level 2
10. Drug: PY159/Pembrolizumab Combination dose level 3
11. Drug: PY159/Pembrolizumab Combination dose level 4
12. Drug: PY159 Single agent dose expansion cohort 1
13. Drug: PY159 Single agent dose expansion cohort 2
14. Drug: PY159/Pembrolizumab Combination dose expansion cohort 1
15. Drug: PY159/Pembrolizumab Combination dose expansion cohort 2
16. Drug: PY159/Pembrolizumab Combination dose expansion cohort 3
17. Drug: PY159/Pembrolizumab Combination dose expansion cohort 4

MeSH:Neoplasms

HPO:Neoplasm

drugs targeting EGFR, EGFR, ALK, ROS-1, NTRK, MET, RET and BRAF V600E, Her2neu). --- V600E ---

The purpose of this Treatment Plan is to allow access to trametinib and dabrafenib for eligible high-risk BRAF mutation-positive patients in the adjuvant treatment of melanoma after surgical resection. The patient's Treating Physician should follow the suggested treatment guidelines and comply with all local health authority regulations.

NCT04544202

Conditions

1. Melanoma
2. Adjuvant

Interventions

1. Drug: Dabrafenib and Trametinib
2. Drug: Dabrafenib
3. Drug: Trametinib

MeSH:Melanoma

HPO:Cutaneous melanoma Melanoma

2. Has the following diagnosis: Completely resected (R0) histologically confirmed high-risk (stage III) cutaneous melanoma with confirmed BRAF V600E/K activating mutation. --- V600E ---

The purpose of this study is to find out whether a drug called PDR001, combined with either trametinib or dabrafenib, is a safe and effective treatment for thyroid cancer.

NCT04544111

Conditions

1. Thyroid Cancer
2. Thyroid Cancer, Follicular
3. Papillary Thyroid Cancer
4. Follicular Thyroid Cancer
5. Hurthle Cell Tumor
6. Poorly Differentiated Thyroid Gland Carcinoma
7. Hurthle Cell Thyroid Neoplasia

Interventions

1. Drug: Trametinib
2. Drug: Dabrafenib
3. Drug: PDR001

MeSH:Thyroid Neoplasms Thyroid Cancer, Papillary Adenocarcinoma, Follicular Adenoma, Oxyphilic Thyroid Diseases

HPO:Abnormality of the thyroid gland Follicular thyroid carcinoma Neoplasm of the thyroid gland Thyroid adenoma Thyroid carcinoma Thyroid follicular adenoma

V600E, V600K, V600D). --- V600E ---

The primary objective for this non-interventional study is to assess the quality of life of melanoma patients under adjuvant treatment with dabrafenib and trametinib in real world setting in Portugal through disease specific FACT-M questionnaire and generic EQ-5D-3L questionnaire.The secondary study objectives are to assess the usage of adjuvant dabrafenib and trametinib in clinical practice and to evaluate clinical outcomes in patients that start adjuvant treatment with dabrafenib and trametinib. In addition, this study aims to explore if treatment discontinuation affects clinical outcomes in real-world practice.

NCT04547946

Conditions

1. Malignant Melanoma

Interventions

1. Drug: dabrafenib + trametinib

MeSH:Melanoma

HPO:Cutaneous melanoma Melanoma

Inclusion Criteria: - Patients with complete surgical resection of histologically confirmed AJCC (8th edition) clinical stage III (IIIA, IIIB, IIIC, IIID) melanoma, in whom a decision for adjuvant treatment with dabrafenib and trametinib has been made before entering the study - V600E/K mutation-positive cutaneous melanoma - Adjuvant treatment with combination therapy of Dabrafenib (Tafinlar®) and Trametinib (Mekinist®) as indicated in the SmPC and by prescription, that has been started before inclusion of the patient into the study; - ≥ 18 years of age - Written informed consent signed. --- V600E ---

RATIONALE: Studying samples of tissue in the laboratory from patients who received cetuximab may help doctors understand and predict how well patients will respond to treatment. PURPOSE: This research study is studying biomarkers in predicting response to cetuximab in patients with advanced colorectal cancer.

NCT01243372

Conditions

1. Colorectal Cancer

Interventions

1. Genetic: mutation analysis
2. Other: laboratory biomarker analysis

MeSH:Colorectal Neoplasms

HPO:Neoplasm of the large intestine

DISEASE CHARACTERISTICS: - Participation in CALGB-C80405 - Have KRAS WT or KRAS mut tumor - Randomized to treatment with either bevacizumab or cetuximab alone - Patients randomized to the combination therapy are not eligible - Available specimens at the PCO for BRAF mutation detection - Patient consent for use of samples DISEASE CHARACTERISTICS: - Participation in CALGB-C80405 - Have KRAS WT or KRAS mut tumor - Randomized to treatment with either bevacizumab or cetuximab alone - Patients randomized to the combination therapy are not eligible - Available specimens at the PCO for BRAF mutation detection - Patient consent for use of samples Colorectal Cancer Colorectal Neoplasms OBJECTIVES: Primary - To determine, among patients with advanced CRC, whether the effect of treatment (cetuximab vs bevacizumab) on progression-free survival (PFS) depends on tumor BRAF V600E mutational status. --- V600E ---

Secondary - To study the relationships between tumor BRAF V600E mutational status, OS, and tumor response. --- V600E ---

Previously collected formalin-fixed and paraffin-embedded baseline tumor samples are analyzed for BRAF V600E mutation. --- V600E ---

This is a two-arm, open-label, randomized Phase III study comparing single agent GSK1120212 to chemotherapy (either dacarbazine or paclitaxel) in subjects with Stage IIIc or Stage IV malignant cutaneous melanoma. All subjects must have a BRAF mutation-positive tumour sample. Subjects who have received up to one prior regimen of chemotherapy in the advanced or metastatic melanoma setting will be enrolled into the study. Subjects with any prior BRAF or MEK inhibitor use will be excluded. Approximately 297 subjects will be enrolled with 2:1 randomization (198 subjects into the GSK1120212 arm and 99 subjects into the chemotherapy arm). The primary endpoint for the statistical analysis will be a comparison of progression free survival for subjects receiving GSK1120212 compared to chemotherapy. Subjects who have progression on chemotherapy will be offered the option to receive GSK1120212.

NCT01245062

Conditions

1. Melanoma

Interventions

1. Drug: GSK1120212
2. Drug: Chemotherapy

MeSH:Melanoma

HPO:Cutaneous melanoma Melanoma

A Phase III Randomized, Open-label Study Comparing GSK1120212 to Chemotherapy in Subjects With Advanced or Metastatic BRAF V600E/K Mutation-positive Melanoma. --- V600E ---

GSK1120212 vs Chemotherapy in Advanced or Metastatic BRAF V600E/K Mutation-positive Melanoma This is a two-arm, open-label, randomized Phase III study comparing single agent GSK1120212 to chemotherapy (either dacarbazine or paclitaxel) in subjects with Stage IIIc or Stage IV malignant cutaneous melanoma. --- V600E ---

Progression-free Survival in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases as Assessed by the Investigator and Independent Review. --- V600E ---

Primary Efficacy Population included all participants with BRAF V600E mutation-positive melanoma without a history of brain metastases.. Progression-free Survival in All Participants. --- V600E ---

Intend-To-Treat (ITT) Population included all randomized participants regardless of whether or not treatment was administered.. PFS in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases and Without Prior Chemotherapy as Assessed by the Investigator. --- V600E ---

PD is defined as at least a 20% increase in the sum of the diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions, or the worsening of non-target lesions significant enough to require study treatment discontinuation.. PFS in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases and With Prior Chemotherapy as Assessed by the Investigator. --- V600E ---

Overall survival was defined as the time from the date of randomization to the date of death due to any cause.. Overall Survival in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases. --- V600E ---

NA indicates data was not available.. Number of BRAF V600E Mutation-positive Participants Without a History of Brain Metastases With Overall Response (OR) as Assessed by the Investigator and Independent Review. --- V600E ---

Any pathological lymph node must be less than 10 mm in the short axis) or partial response (at least a 30% decrease in the sum of the diameters of target lesions) evaluated by the Investigator and an independent review per RECIST, Version 1.1.. Number of BRAF V600E Mutation-positive Participants Classified as Confirmed Responders (CR and PR) as Assessed by the Investigator. --- V600E ---

Only participants who received at least one dose of Trametinib were included in this population.. Duration of Response (DoR) for All BRAF V600E Mutation-positive Participants Without a Prior History of Brain Metastases Classified as Confirmed Responders (CR or PR) as Assessed by the Investigator Review. --- V600E ---

NA indicates data was not available.. DoR for All BRAF V600E Mutation-positive Participants Without a Prior History of Brain Metastases Classified as Confirmed Responders (CR or PR) as Assessed by the Independent Review. --- V600E ---

PD is defined as at least a 20% increase in the sum of the diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions, or the worsening of non-target lesions significant enough to require study treatment discontinuation.. Inclusion Criteria: - ≥18 years of age - Stage III unresectable (Stage IIIc) or metastatic (Stage IV) cutaneous melanoma which is also determined to be BRAF V600E/K mutation-positive by the central laboratory - Received no prior treatment or up to one prior regimen of chemotherapy for advanced or metastatic melanoma. --- V600E ---

- Intraocular pressure > 21 mm Hg as measured by tonography Inclusion Criteria: - ≥18 years of age - Stage III unresectable (Stage IIIc) or metastatic (Stage IV) cutaneous melanoma which is also determined to be BRAF V600E/K mutation-positive by the central laboratory - Received no prior treatment or up to one prior regimen of chemotherapy for advanced or metastatic melanoma. --- V600E ---

The purpose of the study is to identify a safe and tolerable dose of BMS-908662 in combination with ipilimumab; and then to evaluate the anti-tumor response to BMS-908662 when administered in combination with ipilimumab.

NCT01245556

Conditions

1. Melanoma

Interventions

1. Drug: BMS-908662
2. Drug: BMS-908662
3. Drug: Ipilimumab
4. Drug: Ipilimumab

MeSH:Melanoma

HPO:Cutaneous melanoma Melanoma

Inclusion: - Male and female subjects ≥ 18 years of age with a histologic or cytologic diagnosis of Stage III or Stage IV (unresectable) melanoma - Enrollment to cohort expansion will be limited to only those subjects whose tumors demonstrate the B-Raf V600E mutation - ECOG ≤ 1 - Adequate organ & marrow function Exclusion: - Uncontrolled or significant cardiovascular disease - Cohort expansion: Prior therapy with a RAF inhibitor Inclusion: - Male and female subjects ≥ 18 years of age with a histologic or cytologic diagnosis of Stage III or Stage IV (unresectable) melanoma - Enrollment to cohort expansion will be limited to only those subjects whose tumors demonstrate the B-Raf V600E mutation - ECOG ≤ 1 - Adequate organ & marrow function Exclusion: - Uncontrolled or significant cardiovascular disease - Cohort expansion: Prior therapy with a RAF inhibitor Melanoma Melanoma null --- V600E ---

Inclusion: - Male and female subjects ≥ 18 years of age with a histologic or cytologic diagnosis of Stage III or Stage IV (unresectable) melanoma - Enrollment to cohort expansion will be limited to only those subjects whose tumors demonstrate the B-Raf V600E mutation - ECOG ≤ 1 - Adequate organ & marrow function Exclusion: - Uncontrolled or significant cardiovascular disease - Cohort expansion: Prior therapy with a RAF inhibitor Inclusion: - Male and female subjects ≥ 18 years of age with a histologic or cytologic diagnosis of Stage III or Stage IV (unresectable) melanoma - Enrollment to cohort expansion will be limited to only those subjects whose tumors demonstrate the B-Raf V600E mutation - ECOG ≤ 1 - Adequate organ & marrow function Exclusion: - Uncontrolled or significant cardiovascular disease - Cohort expansion: Prior therapy with a RAF inhibitor Melanoma Melanoma null --- V600E --- --- V600E ---

This is an open-label, non-comparative, multicenter, expanded access study of RO5185426 in patients who have received prior systemic therapy for metastatic melanoma and who have no other satisfactory treatment options.

NCT01248936

Conditions

1. Malignant Melanoma

Interventions

1. Drug: RO5185426

MeSH:Melanoma

HPO:Cutaneous melanoma Melanoma

Participants were assessed for best overall response by investigator as per RECIST v1.1.. Inclusion Criteria: - Histologically confirmed metastatic melanoma with documented BRAF V600E mutation, determined by the cobas BRAF V600 mutation test - Patients with either measurable or non-measurable disease - Adequate recovery from most recent systemic or local treatment for metastatic melanoma - Adequate organ function - For women of childbearing potential, agreement to the use of two acceptable methods of contraception, including one barrier method, during the study and for 6 months after discontinuation of RO5185426 - For men with female partners of childbearing potential, agreement to use a latex condom, and to advise their female partner to use an additional method of contraception during the study and for 6 months after discontinuation of RO5185426 - Negative serum or urine pregnancy test within 7 days of commencement of treatment in premenopausal women. --- V600E ---

Women who are either surgically sterile or have been post-menopausal for at least 1 year are eligible to participate in this study - Agreement not to donate blood or blood products during the study and for at least 6 months after discontinuation of RO5185426; for male patients, agreement not to donate sperm during the study and for at least 6 months after discontinuation of RO5185426 Exclusion Criteria: - Pregnant or breast-feeding - Concurrent anti-tumor therapy - Uncontrolled medical illness - History of congenital prolonged QT syndrome or patients with a mean QTc interval greater than 470 milliseconds at baseline, or ongoing grade 2 or greater cardiac arrhythmia Inclusion Criteria: - Histologically confirmed metastatic melanoma with documented BRAF V600E mutation, determined by the cobas BRAF V600 mutation test - Patients with either measurable or non-measurable disease - Adequate recovery from most recent systemic or local treatment for metastatic melanoma - Adequate organ function - For women of childbearing potential, agreement to the use of two acceptable methods of contraception, including one barrier method, during the study and for 6 months after discontinuation of RO5185426 - For men with female partners of childbearing potential, agreement to use a latex condom, and to advise their female partner to use an additional method of contraception during the study and for 6 months after discontinuation of RO5185426 - Negative serum or urine pregnancy test within 7 days of commencement of treatment in premenopausal women. --- V600E ---

This study aims to determine which of 3 drug combinations best reduces the size of tumour prior to surgery for advanced melanoma and prevents the recurrence of melanoma after surgery.

NCT02858921

Conditions

1. Melanoma

Interventions

1. Drug: Dabrafenib
2. Drug: Trametinib
3. Drug: Pembrolizumab

MeSH:Melanoma

HPO:Cutaneous melanoma Melanoma

A positive V600E immunohistochemistry stain at study entry should be formally quantified with a local molecular test following study entry (e.g. --- V600E ---

Allocation of treatment will be concealed prior to randomisation which will be performed via a web based system in permuted blocks and stratified by BRAF V600E mutation versus non BRAF V600E mutation (i.e. --- V600E ---

Allocation of treatment will be concealed prior to randomisation which will be performed via a web based system in permuted blocks and stratified by BRAF V600E mutation versus non BRAF V600E mutation (i.e. --- V600E --- --- V600E ---

The purpose of this study is to determine the safety of an extracellular signal regulated kinase (ERK1/2) inhibitor LY3214996 administered alone or in combination with other agents in participants with advanced cancer.

NCT02857270

Conditions

1. Advanced Cancer
2. Metastatic Melanoma
3. Metastatic Non-small Cell Lung Cancer
4. Colorectal Cancer

Interventions

1. Drug: LY3214996
2. Drug: Midazolam
3. Drug: Abemaciclib
4. Drug: Nab-paclitaxel
5. Drug: Gemcitabine
6. Drug: Encorafenib
7. Drug: Cetuximab

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

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

- Part E: Metastatic BRAF V600E colorectal cancer. --- V600E ---

This Phase 3, open-label, triple arm study aims to evaluate the overall survival (OS) of fotemustine versus the combination of ipilimumab and fotemustine or the combination of Ipilimumab and nivolumab in patients with metastatic melanoma with brain metastasis.

NCT02460068

Conditions

1. Brain Metastases

Interventions

1. Drug: Fotemustine
2. Drug: Fotemustine and Ipilimumab
3. Drug: Ipilimumab and nivolumab

MeSH:Melanoma Neoplasm Metastasis Neoplasms, Second Primary Brain Neoplasms

HPO:Brain neoplasm Cutaneous melanoma Melanoma

- Subjects must have known BRAF V600E mutation status or consent to BRAF V600E mutation testing per local institutional standard. --- V600E ---

- Subjects must have known BRAF V600E mutation status or consent to BRAF V600E mutation testing per local institutional standard. --- V600E --- --- V600E ---

The purpose of this study is to evaluate the safety and tolerability of imatinib mesylate in combination with panitumumab for the treatment of stage IV colorectal cancer that has spread to the liver. It will also assess the whether imatinib mesylate, either alone or in combination with panitumumab, is effective in treating this type of cancer. In addition, the study will evaluate the feasibility of a predefined lab score and whether it can predict which patients will respond to treatment with imatinib mesylate.

NCT00867334

Conditions

1. Colorectal Neoplasm
2. Colorectal Cancer

Interventions

1. Drug: Imatinib mesylate and panitumumab
2. Drug: Standard-of-care treatment with panitumumab

MeSH:Colorectal Neoplasms

HPO:Neoplasm of the large intestine

Colorectal Neoplasm Colorectal Cancer Colorectal Neoplasms Recently, a series of clinical trial outcome reports have shown that KRAS mutations (and to a lesser extent KRAS mutations with BRAF V600E mutation) significantly negatively correlate with response to anti-epidermal growth factor (EGFR) mAbs, such as panitumumab, in metastatic colorectal cancer (mCRC) patients. --- V600E ---

This phase II trial is studying how well MEK inhibitor AZD6244 works in treating patients with stage III or stage IV melanoma. MEK inhibitor AZD6244 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

NCT00866177

Conditions

1. Recurrent Melanoma
2. Stage III Skin Melanoma
3. Stage IV Skin Melanoma

Interventions

1. Other: Laboratory Biomarker Analysis
2. Drug: Selumetinib

MeSH:Melanoma Skin Neoplasms

HPO:Cutaneous melanoma Melanoma Neoplasm of the skin

Inclusion Criteria: - Histologically or cytologically confirmed melanoma - Stage IV or stage III disease not potentially curable with surgery - Documented tumor progression - Must have a V600E or V600K BRAF-mutated tumor, or a NRAS mutation at condons 12, 13, or 61 - Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan - Must have tumor tissue (block or unstained slides) available for IHC studies - No primary uveal or mucosal melanoma - No active or untreated brain metastases - Treated brain metastases allowed provided they have been stable for ≥ 3 months - ECOG performance status 0-1 - Life expectancy > 3 months - WBC ≥ 3,000/mcL - Absolute neutrophil count ≥ 1,500/mcL - Platelet count ≥ 100,000/mcL - Hemoglobin ≥ 9.0 g/dL (no requirement for transfusions within the past 2 weeks) - Total bilirubin ≤ 1.5 times upper limit of normal (ULN) - AST/ALT ≤ 2.5 times ULN - Creatinine ≤ 1.5 mg/dL - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 16 weeks after completion of study treatment - No refractory nausea and vomiting, chronic gastrointestinal disease (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption - No concurrent uncontrolled illness, including, but not limited to, any of the following: - Ongoing or active infection or bleeding - Symptomatic congestive heart failure - Unstable angina pectoris - Cardiac arrhythmia - Psychiatric illness/social situation that would limit compliance with study requirements - No history of allergic reactions attributed to compounds of similar chemical or biologic composition to MEK inhibitor AZD6244 - Any number of prior therapies allowed - At least 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered - At least 4 months since prior anti-CTLA4 monoclonal antibody therapy - At least 4 weeks since other prior systemic therapy - No other concurrent investigational agents - No concurrent antiretroviral therapy for HIV-positive patients - No concurrent vitamin E supplementation or multivitamin supplements that provide a total daily dose in excess of 100% of the recommended daily dose of vitamin E - No concurrent anticancer chemotherapy or other systemic drugs - Concurrent palliative radiotherapy allowed Inclusion Criteria: - Histologically or cytologically confirmed melanoma - Stage IV or stage III disease not potentially curable with surgery - Documented tumor progression - Must have a V600E or V600K BRAF-mutated tumor, or a NRAS mutation at condons 12, 13, or 61 - Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan - Must have tumor tissue (block or unstained slides) available for IHC studies - No primary uveal or mucosal melanoma - No active or untreated brain metastases - Treated brain metastases allowed provided they have been stable for ≥ 3 months - ECOG performance status 0-1 - Life expectancy > 3 months - WBC ≥ 3,000/mcL - Absolute neutrophil count ≥ 1,500/mcL - Platelet count ≥ 100,000/mcL - Hemoglobin ≥ 9.0 g/dL (no requirement for transfusions within the past 2 weeks) - Total bilirubin ≤ 1.5 times upper limit of normal (ULN) - AST/ALT ≤ 2.5 times ULN - Creatinine ≤ 1.5 mg/dL - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 16 weeks after completion of study treatment - No refractory nausea and vomiting, chronic gastrointestinal disease (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption - No concurrent uncontrolled illness, including, but not limited to, any of the following: - Ongoing or active infection or bleeding - Symptomatic congestive heart failure - Unstable angina pectoris - Cardiac arrhythmia - Psychiatric illness/social situation that would limit compliance with study requirements - No history of allergic reactions attributed to compounds of similar chemical or biologic composition to MEK inhibitor AZD6244 - Any number of prior therapies allowed - At least 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered - At least 4 months since prior anti-CTLA4 monoclonal antibody therapy - At least 4 weeks since other prior systemic therapy - No other concurrent investigational agents - No concurrent antiretroviral therapy for HIV-positive patients - No concurrent vitamin E supplementation or multivitamin supplements that provide a total daily dose in excess of 100% of the recommended daily dose of vitamin E - No concurrent anticancer chemotherapy or other systemic drugs - Concurrent palliative radiotherapy allowed Recurrent Melanoma Stage III Skin Melanoma Stage IV Skin Melanoma Melanoma Skin Neoplasms PRIMARY OBJECTIVES: I. Determine the response in patients with V600E or V600K BRAF-mutated or NRAS-mutated stage III or stage IV melanoma with low or high phospho-pAKT expression treated with MEK inhibitor AZD6244. --- V600E ---

Inclusion Criteria: - Histologically or cytologically confirmed melanoma - Stage IV or stage III disease not potentially curable with surgery - Documented tumor progression - Must have a V600E or V600K BRAF-mutated tumor, or a NRAS mutation at condons 12, 13, or 61 - Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan - Must have tumor tissue (block or unstained slides) available for IHC studies - No primary uveal or mucosal melanoma - No active or untreated brain metastases - Treated brain metastases allowed provided they have been stable for ≥ 3 months - ECOG performance status 0-1 - Life expectancy > 3 months - WBC ≥ 3,000/mcL - Absolute neutrophil count ≥ 1,500/mcL - Platelet count ≥ 100,000/mcL - Hemoglobin ≥ 9.0 g/dL (no requirement for transfusions within the past 2 weeks) - Total bilirubin ≤ 1.5 times upper limit of normal (ULN) - AST/ALT ≤ 2.5 times ULN - Creatinine ≤ 1.5 mg/dL - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 16 weeks after completion of study treatment - No refractory nausea and vomiting, chronic gastrointestinal disease (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption - No concurrent uncontrolled illness, including, but not limited to, any of the following: - Ongoing or active infection or bleeding - Symptomatic congestive heart failure - Unstable angina pectoris - Cardiac arrhythmia - Psychiatric illness/social situation that would limit compliance with study requirements - No history of allergic reactions attributed to compounds of similar chemical or biologic composition to MEK inhibitor AZD6244 - Any number of prior therapies allowed - At least 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered - At least 4 months since prior anti-CTLA4 monoclonal antibody therapy - At least 4 weeks since other prior systemic therapy - No other concurrent investigational agents - No concurrent antiretroviral therapy for HIV-positive patients - No concurrent vitamin E supplementation or multivitamin supplements that provide a total daily dose in excess of 100% of the recommended daily dose of vitamin E - No concurrent anticancer chemotherapy or other systemic drugs - Concurrent palliative radiotherapy allowed Inclusion Criteria: - Histologically or cytologically confirmed melanoma - Stage IV or stage III disease not potentially curable with surgery - Documented tumor progression - Must have a V600E or V600K BRAF-mutated tumor, or a NRAS mutation at condons 12, 13, or 61 - Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan - Must have tumor tissue (block or unstained slides) available for IHC studies - No primary uveal or mucosal melanoma - No active or untreated brain metastases - Treated brain metastases allowed provided they have been stable for ≥ 3 months - ECOG performance status 0-1 - Life expectancy > 3 months - WBC ≥ 3,000/mcL - Absolute neutrophil count ≥ 1,500/mcL - Platelet count ≥ 100,000/mcL - Hemoglobin ≥ 9.0 g/dL (no requirement for transfusions within the past 2 weeks) - Total bilirubin ≤ 1.5 times upper limit of normal (ULN) - AST/ALT ≤ 2.5 times ULN - Creatinine ≤ 1.5 mg/dL - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 16 weeks after completion of study treatment - No refractory nausea and vomiting, chronic gastrointestinal disease (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption - No concurrent uncontrolled illness, including, but not limited to, any of the following: - Ongoing or active infection or bleeding - Symptomatic congestive heart failure - Unstable angina pectoris - Cardiac arrhythmia - Psychiatric illness/social situation that would limit compliance with study requirements - No history of allergic reactions attributed to compounds of similar chemical or biologic composition to MEK inhibitor AZD6244 - Any number of prior therapies allowed - At least 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered - At least 4 months since prior anti-CTLA4 monoclonal antibody therapy - At least 4 weeks since other prior systemic therapy - No other concurrent investigational agents - No concurrent antiretroviral therapy for HIV-positive patients - No concurrent vitamin E supplementation or multivitamin supplements that provide a total daily dose in excess of 100% of the recommended daily dose of vitamin E - No concurrent anticancer chemotherapy or other systemic drugs - Concurrent palliative radiotherapy allowed Recurrent Melanoma Stage III Skin Melanoma Stage IV Skin Melanoma Melanoma Skin Neoplasms PRIMARY OBJECTIVES: I. Determine the response in patients with V600E or V600K BRAF-mutated or NRAS-mutated stage III or stage IV melanoma with low or high phospho-pAKT expression treated with MEK inhibitor AZD6244. --- V600E --- --- V600K --- --- V600E ---

Inclusion Criteria: - Histologically or cytologically confirmed melanoma - Stage IV or stage III disease not potentially curable with surgery - Documented tumor progression - Must have a V600E or V600K BRAF-mutated tumor, or a NRAS mutation at condons 12, 13, or 61 - Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan - Must have tumor tissue (block or unstained slides) available for IHC studies - No primary uveal or mucosal melanoma - No active or untreated brain metastases - Treated brain metastases allowed provided they have been stable for ≥ 3 months - ECOG performance status 0-1 - Life expectancy > 3 months - WBC ≥ 3,000/mcL - Absolute neutrophil count ≥ 1,500/mcL - Platelet count ≥ 100,000/mcL - Hemoglobin ≥ 9.0 g/dL (no requirement for transfusions within the past 2 weeks) - Total bilirubin ≤ 1.5 times upper limit of normal (ULN) - AST/ALT ≤ 2.5 times ULN - Creatinine ≤ 1.5 mg/dL - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 16 weeks after completion of study treatment - No refractory nausea and vomiting, chronic gastrointestinal disease (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption - No concurrent uncontrolled illness, including, but not limited to, any of the following: - Ongoing or active infection or bleeding - Symptomatic congestive heart failure - Unstable angina pectoris - Cardiac arrhythmia - Psychiatric illness/social situation that would limit compliance with study requirements - No history of allergic reactions attributed to compounds of similar chemical or biologic composition to MEK inhibitor AZD6244 - Any number of prior therapies allowed - At least 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered - At least 4 months since prior anti-CTLA4 monoclonal antibody therapy - At least 4 weeks since other prior systemic therapy - No other concurrent investigational agents - No concurrent antiretroviral therapy for HIV-positive patients - No concurrent vitamin E supplementation or multivitamin supplements that provide a total daily dose in excess of 100% of the recommended daily dose of vitamin E - No concurrent anticancer chemotherapy or other systemic drugs - Concurrent palliative radiotherapy allowed Inclusion Criteria: - Histologically or cytologically confirmed melanoma - Stage IV or stage III disease not potentially curable with surgery - Documented tumor progression - Must have a V600E or V600K BRAF-mutated tumor, or a NRAS mutation at condons 12, 13, or 61 - Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan - Must have tumor tissue (block or unstained slides) available for IHC studies - No primary uveal or mucosal melanoma - No active or untreated brain metastases - Treated brain metastases allowed provided they have been stable for ≥ 3 months - ECOG performance status 0-1 - Life expectancy > 3 months - WBC ≥ 3,000/mcL - Absolute neutrophil count ≥ 1,500/mcL - Platelet count ≥ 100,000/mcL - Hemoglobin ≥ 9.0 g/dL (no requirement for transfusions within the past 2 weeks) - Total bilirubin ≤ 1.5 times upper limit of normal (ULN) - AST/ALT ≤ 2.5 times ULN - Creatinine ≤ 1.5 mg/dL - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 16 weeks after completion of study treatment - No refractory nausea and vomiting, chronic gastrointestinal disease (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption - No concurrent uncontrolled illness, including, but not limited to, any of the following: - Ongoing or active infection or bleeding - Symptomatic congestive heart failure - Unstable angina pectoris - Cardiac arrhythmia - Psychiatric illness/social situation that would limit compliance with study requirements - No history of allergic reactions attributed to compounds of similar chemical or biologic composition to MEK inhibitor AZD6244 - Any number of prior therapies allowed - At least 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered - At least 4 months since prior anti-CTLA4 monoclonal antibody therapy - At least 4 weeks since other prior systemic therapy - No other concurrent investigational agents - No concurrent antiretroviral therapy for HIV-positive patients - No concurrent vitamin E supplementation or multivitamin supplements that provide a total daily dose in excess of 100% of the recommended daily dose of vitamin E - No concurrent anticancer chemotherapy or other systemic drugs - Concurrent palliative radiotherapy allowed Recurrent Melanoma Stage III Skin Melanoma Stage IV Skin Melanoma Melanoma Skin Neoplasms PRIMARY OBJECTIVES: I. Determine the response in patients with V600E or V600K BRAF-mutated or NRAS-mutated stage III or stage IV melanoma with low or high phospho-pAKT expression treated with MEK inhibitor AZD6244. --- V600E --- --- V600K --- --- V600E --- --- V600K --- --- V600E ---

Whole-genome and transcriptome sequencing of patients with advanced solid tumors enrolled in the NCT/DKTK MASTER (Molecularly Aided Stratification for Tumor Eradication Research) program revealed genetic alterations in a substantial proportion of patients including (i) alterations that lead to aberrant activation of BRAF, ERBB2, ALK, and the PI3K-AKT and MAPK pathways and (ii) changes that predict sensitivity to immune checkpoint inhibition, such as high tumor mutational burden and specific alterations of the PD-L1 locus. Within this seven-arm basket phase II clinical trial, we aim to investigate the efficacy of targeted-therapy plus immune checkpoint inhibition in patients with advanced tumors exhibiting one of the following genetic alterations detected within the NCT/DKTK MASTER study: (i) BRAF V600E/K, (ii)ERBB2 amplification and/or overexpression or activating ERBB2 mutation, (iii) ALK rearrangement or activating ALK mutation, (iv) activating PIK3CA or AKT mutations or other aberration predicting increased PI3K-AKT pathway activity, (v) abberations predicting increased RAF-MEK-ERK pathway activity; (vi) patients with high tumor mutational burden and/or specific alteration predicting sensitivity to PD-1/PD-L1 inhibition are eligible within this study for immune checkpoint inhibition. Recruitment of adequate patient numbers into these well-defined molecular subgroup is achieved in a multicenter approach including NCT Heidelberg and NCT Dresden as well as DKTK partner sites. Eligible patients will be identified by in-depth molecular characterization of tumors within the NCT/DKTK MASTER program. All study arms are based on similar biometrical assumptions, and sample size as well as power calculations are based on Simon's optimal two-stage design for each study arm separately. The overall aim is to reduce the cumulative hazard of progression-free survival observed within the study (PFS2) compared to the cumulative hazard of the progression-free time before inclusion into the study (PFS1) using a paired log-rank test. The sample size of the entire trial varies according to the performance of the individual study arms, ranging between 98 and 175 patients.

NCT04551521

Conditions

1. Metastatic or Locally Advanced Malignancies

Interventions

1. Drug: Vemurafenib
2. Drug: Cobimetinib
3. Drug: Atezolizumab
4. Drug: Trastuzumab
5. Drug: Pertuzumab
6. Drug: Alectinib
7. Drug: Ipatasertib
8. Drug: Cobimetinib
9. Drug: Atezolizumab
10. Drug: Atezolizumab
11. Drug: Atezolizumab
12. Drug: Ipatasertib
13. Drug: Atezolizumab
14. Drug: Atezolizumab

MeSH:Neoplasms

HPO:Neoplasm

Within this seven-arm basket phase II clinical trial, we aim to investigate the efficacy of targeted-therapy plus immune checkpoint inhibition in patients with advanced tumors exhibiting one of the following genetic alterations detected within the NCT/DKTK MASTER study: (i) BRAF V600E/K, (ii)ERBB2 amplification and/or overexpression or activating ERBB2 mutation, (iii) ALK rearrangement or activating ALK mutation, (iv) activating PIK3CA or AKT mutations or other aberration predicting increased PI3K-AKT pathway activity, (v) abberations predicting increased RAF-MEK-ERK pathway activity; (vi) patients with high tumor mutational burden and/or specific alteration predicting sensitivity to PD-1/PD-L1 inhibition are eligible within this study for immune checkpoint inhibition. --- V600E ---

- Arm 1 (BRAF V600E/K): BRAF V600E/K mutation - Arm 2 (ERBB2): ERBB2 amplification/overexpression, activating ERBB2 mutation - Arm 3 (ALK): ALK rearrangement or activating ALK mutations including alternative transcription initiation (ALK-ATI) or RET-fusions - Arm 4 (PI3K-AKT): Activating PIK3CA or AKT mutations; other aberrations predicting increased PI3K-AKT pathway activity, e.g. --- V600E ---

- Arm 1 (BRAF V600E/K): BRAF V600E/K mutation - Arm 2 (ERBB2): ERBB2 amplification/overexpression, activating ERBB2 mutation - Arm 3 (ALK): ALK rearrangement or activating ALK mutations including alternative transcription initiation (ALK-ATI) or RET-fusions - Arm 4 (PI3K-AKT): Activating PIK3CA or AKT mutations; other aberrations predicting increased PI3K-AKT pathway activity, e.g. --- V600E --- --- V600E ---

PTEN lossa - Arm 6 (MAPK): Aberrations other than BRAF V600E/K predicting increased RAF-MEK- ERK pathway activity - Arm 7 (Immune evasion): High tumor mutational burden and/or specific alterations predicting sensitivity to PD1/PDL1 inhibition (e.g. --- V600E ---

The purpose of the study is to evaluate the efficacy of treatment with abemaciclib in patients with anaplastic thyroid/undifferentiated thyroid

NCT04552769

Conditions

1. Thyroid Cancer
2. Anaplastic Thyroid Cancer
3. Undifferentiated Thyroid Cancer

Interventions

1. Drug: Abemaciclib

MeSH:Thyroid Neoplasms Thyroid Carcinoma, Anaplastic Thyroid Diseases

HPO:Abnormality of the thyroid gland Anaplastic thyroid carcinoma Neoplasm of the thyroid gland Thyroid adenoma Thyroid carcinoma Thyroid follicular adenoma

This will be reported as median time with interquartile range.. Inclusion Criteria: 1. Histologically or cytologically confirmed diagnosis of anaplastic thyroid cancer or undifferentiated thyroid cancer that does not have a known BRAF V600E positive on tissue/blood testing. --- V600E ---

BRAF V600E positive patients are eligible if they have previously received FDA approved therapy for this genetic abnormality and progressed or become intolerant. --- V600E ---

Inclusion Criteria: 1. Histologically or cytologically confirmed diagnosis of anaplastic thyroid cancer or undifferentiated thyroid cancer that does not have a known BRAF V600E positive on tissue/blood testing. --- V600E ---

This research study is studying a combination of drugs as a possible treatment for BRAF-mutant melanoma. The drugs involved in this study are: - Itacitinib (INCB039110) - Dabrafenib - Trametinib

NCT03272464

Conditions

1. Melanoma

Interventions

1. Drug: Trametinib
2. Drug: Dabrafenib
3. Drug: INCB039110

MeSH:Melanoma

HPO:Cutaneous melanoma Melanoma

Inclusion Criteria: - For Dose-Escalation Phase: Patients must have histologically confirmed, BRAF-mutant (V600E/K) malignancy (molecularly confirmed using Cobas assay or a comparable FDA-approved assay (for exceptions, see below*) that is metastatic or unresectable, have received and tolerated prior BRAF or BRAF and MEK inhibitor (BRAF targeted) therapy or not previously received BRAF targeted therapy, and for which standard curative or palliative measures do not exist or are no longer effective. --- V600E ---

- For Dose-Expansion Phase: Patients must have histologically confirmed, BRAF-mutant (V600E/K) melanoma (molecularly confirmed using Cobas assay or a comparable FDA-approved assay (for exceptions, see below*) that is metastatic or unresectable, have received and tolerated prior BRAF or BRAF and MEK inhibitor (BRAF targeted) therapy at full dose or not previously received BRAF targeted therapy. --- V600E ---

Current use of, or intended ongoing treatment with: herbal remedies (e.g., St. John's wort), or strong inhibitors or inducers of P-glycoprotein (Pgp) or breast cancer resistance protein 1 (Bcrp1) should also be excluded Inclusion Criteria: - For Dose-Escalation Phase: Patients must have histologically confirmed, BRAF-mutant (V600E/K) malignancy (molecularly confirmed using Cobas assay or a comparable FDA-approved assay (for exceptions, see below*) that is metastatic or unresectable, have received and tolerated prior BRAF or BRAF and MEK inhibitor (BRAF targeted) therapy or not previously received BRAF targeted therapy, and for which standard curative or palliative measures do not exist or are no longer effective. --- V600E ---

This is a Phase 1 study of JSI-1187 as monotherapy and in combination with dabrafenib for the treatment of advanced solid tumors with MAPK pathway mutations, including mutations that cause MAPK pathway hyperactivation.

NCT04418167

Conditions

1. Solid Tumors

Interventions

1. Drug: JSI-1187
2. Drug: Dabrafenib

MeSH:Neoplasms

HPO:Neoplasm

In consenting subjects and when clinically available, tumor biopsies will be taken pre-study and on study to assess change in tumor pRSK.. Inclusion Criteria: - Males and females ≥ 18 years of age - Have locally advanced or metastatic solid tumor malignancy with measurable disease and be an appropriate candidate for experimental therapy - Part A (JSI-1187 Monotherapy Dose Escalation): Histologically or cytologically confirmed MAPK pathway mutation, including hyperactivating pathway mutations or gene fusions, e.g., BRAF (Class I, II or III), RAS (H/K/N), MEK (MAP2K1), RAS-GAP (NF1 loss, RASA1), RAS-GEF, refractory to or relapsed on prior therapy, and have received all available therapy known to confer clinical benefit - Part B (JSI-1187 Plus Dabrafenib Combination Dose Escalation): Histologically or cytologically confirmed BRAF V600-mutated locally advanced or metastatic solid tumor, refractory to, or relapsed on, prior therapy, and have received all available therapy known to confer clinical benefit - Part C (JSI-1187 Plus Dabrafenib Expansion Cohorts): Histologically or cytologically confirmed: - Cohort 1: BRAF V600-mutated metastatic melanoma after two prior therapies for metastatic disease, including anti-PD1 therapy, with or without ipilimumab, and BRAF/MEK inhibitor treatment - Cohort 2: BRAF V600-mutated metastatic melanoma after adjuvant therapy for Stage 3 disease followed by one prior therapy for metastatic disease, including anti-PD-1 therapy, with or without ipilimumab or BRAF/MEK inhibitor treatment - Cohort 3: Either BRAF V600E-mutated metastatic non-small cell lung cancer (NSCLC), or BRAF V600-mutated metastatic solid tumor, after 1 or 2 prior therapies - MAPK mutation tumor status will be established prior to entry based on previous MAPK pathway mutation reports from a CLIA qualified laboratory, or, if a report is not available, the mutation analysis will be performed at Screening on archival tissue or newly biopsied tumor tissue. --- V600E ---

- If female, pregnant, breast-feeding, or planning to become pregnant Inclusion Criteria: - Males and females ≥ 18 years of age - Have locally advanced or metastatic solid tumor malignancy with measurable disease and be an appropriate candidate for experimental therapy - Part A (JSI-1187 Monotherapy Dose Escalation): Histologically or cytologically confirmed MAPK pathway mutation, including hyperactivating pathway mutations or gene fusions, e.g., BRAF (Class I, II or III), RAS (H/K/N), MEK (MAP2K1), RAS-GAP (NF1 loss, RASA1), RAS-GEF, refractory to or relapsed on prior therapy, and have received all available therapy known to confer clinical benefit - Part B (JSI-1187 Plus Dabrafenib Combination Dose Escalation): Histologically or cytologically confirmed BRAF V600-mutated locally advanced or metastatic solid tumor, refractory to, or relapsed on, prior therapy, and have received all available therapy known to confer clinical benefit - Part C (JSI-1187 Plus Dabrafenib Expansion Cohorts): Histologically or cytologically confirmed: - Cohort 1: BRAF V600-mutated metastatic melanoma after two prior therapies for metastatic disease, including anti-PD1 therapy, with or without ipilimumab, and BRAF/MEK inhibitor treatment - Cohort 2: BRAF V600-mutated metastatic melanoma after adjuvant therapy for Stage 3 disease followed by one prior therapy for metastatic disease, including anti-PD-1 therapy, with or without ipilimumab or BRAF/MEK inhibitor treatment - Cohort 3: Either BRAF V600E-mutated metastatic non-small cell lung cancer (NSCLC), or BRAF V600-mutated metastatic solid tumor, after 1 or 2 prior therapies - MAPK mutation tumor status will be established prior to entry based on previous MAPK pathway mutation reports from a CLIA qualified laboratory, or, if a report is not available, the mutation analysis will be performed at Screening on archival tissue or newly biopsied tumor tissue. --- V600E ---

Cohort 3: JSI-1187 plus dabrafenib in either BRAF V600E-mutated non-small cell lung cancer (NSCLC) or BRAF V600-mutated solid tumors after 1 or 2 prior therapies. --- V600E ---

A Phase 1a/1b Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PY314 as a Single Agent and In Combination with Pembrolizumab in Subjects with Advanced Solid Tumors

NCT04691375

Conditions

1. Advanced Solid Tumor

Interventions

1. Drug: Dose of PY314

MeSH:Neoplasms

HPO:Neoplasm

drugs targeting EGFR, EGFR, ALK, ROS-1, NTRK, MET, RET and BRAF V600E, Her2neu)). --- V600E ---

This phase II MATCH treatment trial identifies the effects of trametinib and dabrafenib in patients whose cancer has genetic changes called BRAF V600 mutations. Dabrafenib may stop the growth of cancer by blocking BRAF proteins which may be needed for cell growth. Trametinib may stop the growth of cancer cells by blocking MEK proteins which, in addition to BRAF proteins, may also be needed for cell growth. Researchers hope to learn if giving trametinib with dabrafenib will shrink this type of cancer or stop its growth.

NCT04439292

Conditions

1. Advanced Lymphoma
2. Advanced Malignant Solid Neoplasm
3. Hematopoietic and Lymphoid Cell Neoplasm
4. Refractory Lymphoma
5. Refractory Malignant Solid Neoplasm
6. Refractory Plasma Cell Myeloma

Interventions

1. Drug: Dabrafenib Mesylate
2. Drug: Trametinib Dimethyl Sulfoxide

MeSH:Lymphoma Neoplasms Multiple Myel Multiple Myeloma Neoplasms, Plasma Cell

HPO:Lymphoma Multiple myeloma Neoplasm

MATCH Treatment Subprotocol H: Phase II Study of Dabrafenib and Trametinib in Patients With Tumors With BRAF V600E or V600K Mutations (Excluding Melanoma, Thyroid Cancer, Colorectal Adenocarcinoma, and Non-Small Cell Lung Cancer). --- V600E ---

PFS will be estimated using the Kaplan-Meier method.. Inclusion Criteria: - Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol - Patients must have a BRAF V600E or, V600K, V600R or V600D mutation, or another aberration, as identified via the MATCH Master Protocol - Prothrombin time (PT)/International normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.3 x institutional ULN; subjects receiving anticoagulation treatment may be allowed to participate with INR established within the therapeutic range prior to registration to treatment - Patients must have an ECHO or a nuclear study (multigated aquisition scan [MUGA] or First Pass) within 4 weeks prior to registration to treatment and must not have a left ventricular ejection fraction (LVEF) < the institutional lower limit of normal (LLN). --- V600E ---

However, if the results of previous RAS testing are known, they must be used in assessing eligibility Inclusion Criteria: - Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol - Patients must have a BRAF V600E or, V600K, V600R or V600D mutation, or another aberration, as identified via the MATCH Master Protocol - Prothrombin time (PT)/International normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.3 x institutional ULN; subjects receiving anticoagulation treatment may be allowed to participate with INR established within the therapeutic range prior to registration to treatment - Patients must have an ECHO or a nuclear study (multigated aquisition scan [MUGA] or First Pass) within 4 weeks prior to registration to treatment and must not have a left ventricular ejection fraction (LVEF) < the institutional lower limit of normal (LLN). --- V600E ---

This study has two parts: dose escalation and dose expansion. The primary objectives are: - For Dose Escalation, to assess the safety and tolerability of DS-1205c when combined with osimertinib in the study population and to determine the recommended dose for expansion of DS-1205c when combined with osimertinib in the study population - For Dose Expansion, to assess the safety and tolerability of DS-1205c when combined with osimertinib in the study population In Dose Escalation, after a 7-day run in period (Cycle 0), there will be 21-day cycles (Cycle 1 onward). In Dose Expansion, there will be 21-day cycles. The number of treatment cycles is not fixed in this study. Participants will continue study treatment until they decide not to (withdraw consent), their disease gets worse [progressive disease (PD)], or side effects become unacceptable (unacceptable toxicity).

NCT03255083

Conditions

1. Non-small Cell Lung Cancer (NSCLC)

Interventions

1. Drug: DS-1205c
2. Drug: Osimertinib

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

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

2. Has previously documented evidence of anaplastic lymphoma kinase (ALK) fusion, ROS proto-oncogene 1 (ROS1) fusion, BRAF V600E mutation, rearranged during transfection (RET) rearrangement, human epidermal growth factor receptor 2 (HER2) mutation, or MET exon 14 skipping mutation. --- V600E ---

Dabrafenib is a potent and selective inhibitor of BRAF kinase activity. This is a Phase II, non-randomized, open-label study to assess the efficacy, safety, and tolerability of dabrafenib administered as a single agent and in combination with trametinib in stage IV disease to subjects with BRAF mutant advanced non-small cell lung cancer. Subjects will receive dabrafenib 150 mg twice daily (BID) in monotherapy treatment and dabrafenib 150 mg bid and trametinib 2 mg once daily in combination therapy and continue on treatment until disease progression, death, or unacceptable adverse event.

NCT01336634

Conditions

1. Cancer

Interventions

1. Drug: Dabrafenib
2. Device: Trametinib

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

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

A Phase II Study of the BRAF Inhibitor Dabrafenib as a Single Agent and in Combination With the MEK Inhibitor Trametinib in Subjects With BRAF V600E Mutation Positive Metastatic (Stage IV) Non-small Cell Lung Cancer. --- V600E ---

Study of Selective BRAF Kinase Inhibitor Dabrafenib Monotherapy Twice Daily and in Combination With Dabrafenib Twice Daily and Trametinib Once Daily in Combination Therapy in Subjects With BRAF V600E Mutation Positive Metastatic (Stage IV) Non-small Cell Lung Cancer. --- V600E ---

Subjects in Cohort C will be required to have not received prior systemic anti-cancer therapies for metastatic disease (i.e., dabrafenib/trametinib will be 1st line treatment for metastatic disease); - Measurable disease according to Response Evaluation Criteria in Solid Tumors [RECIST 1.1]; - At least 18 years of age; - Anticipated life expectancy of at least three months; - Presence of a BRAF V600E mutation in lung cancer tissue. --- V600E ---

This is a multicenter, randomized, open-label, 3-arm Phase 3 study to evaluate encorafenib + cetuximab plus or minus binimetinib versus Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab, as controls, in patients with BRAFV600E mCRC whose disease has progressed after 1 or 2 prior regimens in the metastatic setting. The study contains a Safety Lead-in Phase in which the safety and tolerability of encorafenib + binimetinib + cetuximab will be assessed prior to the Phase 3 portion of the study.

NCT02928224

Conditions

1. BRAF V600E-mutant Metastatic Colorectal Cancer

Interventions

1. Drug: Encorafenib
2. Drug: Binimetinib
3. Drug: Cetuximab
4. Drug: Irinotecan
5. Drug: Folinic Acid
6. Drug: 5-Fluorouracil

MeSH:Colorectal Neoplasms

HPO:Neoplasm of the large intestine

A Multicenter, Randomized, Open-label, 3-Arm Phase 3 Study of Encorafenib + Cetuximab Plus or Minus Binimetinib vs. Irinotecan/Cetuximab or Infusional 5- Fluorouracil (5-FU)/Folinic Acid (FA) /Irinotecan (FOLFIRI)/Cetuximab With a Safety Lead-in of Encorafenib + Binimetinib + Cetuximab in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer. --- V600E ---

Study of Encorafenib + Cetuximab Plus or Minus Binimetinib vs. Irinotecan/Cetuximab or Infusional 5-Fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab With a Safety Lead-in of Encorafenib + Binimetinib + Cetuximab in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer This is a multicenter, randomized, open-label, 3-arm Phase 3 study to evaluate encorafenib + cetuximab plus or minus binimetinib versus Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab, as controls, in patients with BRAFV600E mCRC whose disease has progressed after 1 or 2 prior regimens in the metastatic setting. --- V600E ---

An additional study ARRAY-162-105 is not required to register.. Key Inclusion Criteria: - Age ≥ 18 years at time of informed consent - Histologically- or cytologically-confirmed CRC that is metastatic - Presence of BRAFV600E in tumor tissue as previously determined by a local assay at any time prior to Screening or by the central laboratory - Progression of disease after 1 or 2 prior regimens in the metastatic setting - Evidence of measurable or evaluable non-measurable disease per RECIST, v1.1 - Adequate bone marrow, cardiac, kidney and liver function - Able to take oral medications - Female patients are either postmenopausal for at least 1 year, are surgically sterile for at least 6 weeks, or must agree to take appropriate precautions to avoid pregnancy from screening through follow-up if of childbearing potential - Males must agree to take appropriate precautions to avoid fathering a child from screening through follow-up Key Exclusion Criteria: - Prior treatment with any RAF inhibitor, MEK inhibitor, cetuximab, panitumumab or other epidermal growth factor receptor (EGFR) inhibitors - Prior irinotecan hypersensitivity or toxicity that would suggest an inability to tolerate irinotecan 180 mg/m2 every 2 weeks - Symptomatic brain metastasis or leptomeningeal disease - History or current evidence of retinal vein occlusion or current risk factors for retinal vein occlusion (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes) - Known history of acute or chronic pancreatitis - History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤12 months prior to randomization - Uncontrolled blood pressure despite medical treatment - Impaired GI function or disease that may significantly alter the absorption of encorafenib or binimetinib (e.g., ulcerative diseases, uncontrolled vomiting, malabsorption syndrome, small bowel resection with decreased intestinal absorption) - Concurrent or previous other malignancy within 5 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, or other noninvasive or indolent malignancy - History of thromboembolic or cerebrovascular events ≤ 6 months prior to starting study treatment, including transient ischemic attacks, cerebrovascular accidents, deep vein thrombosis or pulmonary emboli - Concurrent neuromuscular disorder that is associated with the potential of elevated creatine (phosphor)kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy) - Residual common terminology criteria for adverse events (CTCAE) ≥ Grade 2 toxicity from any prior anticancer therapy, with the exception of Grade 2 alopecia or Grade 2 neuropathy - Known history of HIV infection - Active hepatitis B or hepatitis C infection - Known history of Gilbert's syndrome - Known contraindication to receive cetuximab or irinotecan at the planned doses Key Inclusion Criteria: - Age ≥ 18 years at time of informed consent - Histologically- or cytologically-confirmed CRC that is metastatic - Presence of BRAFV600E in tumor tissue as previously determined by a local assay at any time prior to Screening or by the central laboratory - Progression of disease after 1 or 2 prior regimens in the metastatic setting - Evidence of measurable or evaluable non-measurable disease per RECIST, v1.1 - Adequate bone marrow, cardiac, kidney and liver function - Able to take oral medications - Female patients are either postmenopausal for at least 1 year, are surgically sterile for at least 6 weeks, or must agree to take appropriate precautions to avoid pregnancy from screening through follow-up if of childbearing potential - Males must agree to take appropriate precautions to avoid fathering a child from screening through follow-up Key Exclusion Criteria: - Prior treatment with any RAF inhibitor, MEK inhibitor, cetuximab, panitumumab or other epidermal growth factor receptor (EGFR) inhibitors - Prior irinotecan hypersensitivity or toxicity that would suggest an inability to tolerate irinotecan 180 mg/m2 every 2 weeks - Symptomatic brain metastasis or leptomeningeal disease - History or current evidence of retinal vein occlusion or current risk factors for retinal vein occlusion (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes) - Known history of acute or chronic pancreatitis - History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤12 months prior to randomization - Uncontrolled blood pressure despite medical treatment - Impaired GI function or disease that may significantly alter the absorption of encorafenib or binimetinib (e.g., ulcerative diseases, uncontrolled vomiting, malabsorption syndrome, small bowel resection with decreased intestinal absorption) - Concurrent or previous other malignancy within 5 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, or other noninvasive or indolent malignancy - History of thromboembolic or cerebrovascular events ≤ 6 months prior to starting study treatment, including transient ischemic attacks, cerebrovascular accidents, deep vein thrombosis or pulmonary emboli - Concurrent neuromuscular disorder that is associated with the potential of elevated creatine (phosphor)kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy) - Residual common terminology criteria for adverse events (CTCAE) ≥ Grade 2 toxicity from any prior anticancer therapy, with the exception of Grade 2 alopecia or Grade 2 neuropathy - Known history of HIV infection - Active hepatitis B or hepatitis C infection - Known history of Gilbert's syndrome - Known contraindication to receive cetuximab or irinotecan at the planned doses BRAF V600E-mutant Metastatic Colorectal Cancer Colorectal Neoplasms null --- V600E ---

In this prospective multicentric study, the University of Pavia together with the Fondazione IRCCS Policlinico San Matteo, Pavia and the IRCCS Fondazione Maugeri, Pavia, Italy will provide a systematic analysis of gene mutations in hematological malignancies by using NGS techniques. Patients with a conclusive diagnosis of haematological malignancies according to WHO criteria referred to the Rete Ematologica Lombarda clinical network (REL, www.rel-lombardia.net) will be enrolled. The investigators will analyse genomic DNA extracted from hematopoietic cells at different time points of patient disease. The study contemplates the use of molecular platforms (Next Generation Sequencing, NGS) aimed at the identification of recurrent mutations in myeloid and lymphoid neoplasms, respectively. Screening of gene mutations by NGS will be prospectively implemented in the context of REL clinical network. Patient samples will be analyzed at diagnosis and sequentially during the course of the disease at specific timepoints. The researchers will analyze the correlations between somatic mutations, specific clinical phenotypes (according to the WHO classification) and disease evolution. This will allow to: 1) identify new recurrent genetic mutations involved in the molecular pathogenesis of hematological malignancies; 2) define the role of mutated genes, distinguishing between genes which induce a clonal proliferation of hematopoietic stem cells, and genes which determine the clinical phenotype of the disease; 3) identify mutations which are responsible for disease evolution; 4) define the diagnostic/prognostic role of the identified mutations, and update the current disease classifications and prognostic scores by including molecular parameters. A systematic biobanking of biological material will be provided.

NCT02459743

Conditions

1. Hematological Malignancies

MeSH:Neoplasms Hematologic Neoplasms

HPO:Hematological neoplasm Leukemia Neoplasm

Moreover in last years, researchers from the University of Pavia gave a significant contribution in the definition of the molecular basis of lymphoid neoplasms (i.e., BRAF V600E mutation in Hairy cell Leukemia, MYD88 L265P mutation in Waldenstrom disease, and SF3B1 mutations in Chronic Lymphocytic Leukemia). --- V600E ---

Present clinical study will be conducted in China to evaluate the pharmacokinetics (PK) of single and repeat oral doses of dabrafenib alone and dabrafenib and trametinib in combination, the safety profile and the clinical activity of dabrafenib in combination with trametinib in Chinese melanoma subjects with BRAF V600E/K mutation. Approximately 20 evaluable subjects will be enrolled in the study, out of which, the first 10 subjects will be enrolled into cohort A (Part I and II) and remaining 10 subjects will be enrolled in cohort B. Subjects in cohort A (Part I) will receive dabrafenib 150 mg twice daily (BID) and subjects in cohort A (Part II) and Cohort B will receive combination of dabrafenib 150 mg BID and trametinib 2 mg once daily (QD). Study treatment will continue until disease progression, death or unacceptable toxicity. After disease progression, all enrolled subjects will be followed up for overall survival. The study will be completed after all subjects have died or surviving subjects have had at least 5 years of follow-up, whichever occurs first.

NCT02447939

Conditions

1. Melanoma

Interventions

1. Drug: Dabrafenib
2. Drug: Trametinib

MeSH:Melanoma

HPO:Cutaneous melanoma Melanoma

Pharmacokinetics of Repeat Oral Doses of Dabrafenib and the Combination of Dabrafenib and Trametinib in Chinese Subjects With Melanoma Present clinical study will be conducted in China to evaluate the pharmacokinetics (PK) of single and repeat oral doses of dabrafenib alone and dabrafenib and trametinib in combination, the safety profile and the clinical activity of dabrafenib in combination with trametinib in Chinese melanoma subjects with BRAF V600E/K mutation. --- V600E ---

- Histologically confirmed cutaneous melanoma that is either Stage IIIC (unresectable) or Stage IV (metastatic), and BRAF V600E/K mutation-positive from the designated qualified laboratory for this study. --- V600E ---

The goal of this multicenter prospective study is to validate, and ultimately translate in routine clinical practice, the use of plasma analysis of ccfDNA for the determination of KRAS mutation status in mCRC patients.

NCT02784639

Conditions

1. Colorectal Cancer

Interventions

1. Other: Plasma Analysis of circulating cell free DNA
2. Other: Tumor tissue analysis of circulating cell free DNA

MeSH:Colorectal Neoplasms

HPO:Neoplasm of the large intestine

As a consequence, the method was adapted to detect the six more frequent KRAS mutations in CRC (G12D, G12V, G13D, G12S, G12C, G12A) and the BRAF V600E. --- G12D --- --- G12V --- --- G13D --- --- G12S --- --- G12C --- --- G12A --- --- V600E ---

CcfDNA analysis showed 100% specificity and sensitivity for the BRAF V600E mutation. --- V600E ---

The study drug, GSK3326595, is an inhibitor of protein arginine methyltransferase 5 (PRMT5) that potently inhibits tumor growth in vitro and in vivo in animal models. This first time in human (FTIH), open-label, dose escalation study will assess the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of GSK3326595 in participants with advanced or recurrent solid tumors, as well as clinical activity in participants with a subset of solid tumors and NHL. This is an open-label, repeat-dose, multicenter, three-part study to establish the maximally tolerated dose (MTD)/ recommended phase 2 dose (RP2D) based on safety and tolerability and preliminary clinical efficacy of orally-administered GSK3326595. Part 1 is a dose-escalation phase to identify the MTD/RP2D based on the safety, PK, and PD profiles observed after oral administration of GSK3326595 and to preliminarily identify whether or not there is an effect of fed versus fasted state and of tablet versus capsule formulation on the PK of GSK3326595. This Part will be conducted in adult participants with relapsed and/or refractory solid tumors. It is estimated that up to 66 participants will be enrolled into the dose escalation cohort of the study, including up to 42 participants to identify the MTD and approximately 12 participants in the PK/PD/metabolite/biomarker expansion cohort(s) and approximately 12 participants in the food effect and relative bioavailability sub-study. Disease-specific expansion cohorts (Part 2) are planned to further explore clinical activity of GSK3326595 in participants with selected solid tumors and NHL. It is estimated that up to 316 participants will be enrolled in Part 2. Part 3 will be a dose determination study to evaluate the safety, PK/PD profile, and clinical activity of orally-administered GSK3326595 in combination with intravenous pembrolizumab. Overall, approximately 30 participants will be enrolled in Part 3. The duration of study will depend on recruitment rates and the timing of participant's duration on study (withdrawal rates due to toxicity or progression), with an approximate duration of 6 years.

NCT02783300

Conditions

1. Neoplasms

Interventions

1. Drug: GSK3326595
2. Drug: Pembrolizumab

MeSH:Lymphoma Lymphoma, Non-Hodgkin

HPO:Lymphoma Non-Hodgkin lymphoma

Tumors with actionable mutations (e.g., BRAF V600E gene mutation in melanoma; Epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements in NSCLC) must have received prior therapy with targeted agents prior to enrollment. --- V600E ---

Colorectal cancer (CRC) is a major public health problem in France and worldwide. CRC is the third most common cancer in incidence and mortality in France. The vast majority of these cancers are adenocarcinomas that arise sporadically and develop from precursor lesions: adenoma. All CCR with the same disease stage do not have the same prognosis. Various parameters have been identified as factors influencing the prognosis and allows adjustment of the treatment. The poor histoprognostic factors are vessels and nerves invasion by the tumor or the mucinous adenocarcinoma subtype. At the molecular level, the presence of microsatellite instability (MSI) improves the prognosis, while the presence of a BRAF mutation is an independent poor prognostic factor. LRP-1 is a multifunctional endocytic receptor that belongs to the family of LDL receptors. It is involved in the clearance of matrix proteases. A loss of expression or a decrease of the LRP-1 activity is correlated with an increase of aggressiveness of cancer cells. This effect was demonstrated in vitro in vesicular thyroid carcinomas after LRP-1 blocking. The decrease in the immunohistochemical expression and LRP-1 genomic in hepatocellular carcinomas and lung adenocarcinomas was correlated with a decrease in the overall survival. In CRC, only one immunohistochemical expression study of LRP-1 in colonic adenocarcinoma has been published to date. This study shows that tumor cells express LRP-1, but in nearly half the cases, weaker than in normal colonic cells. The clinical and prognostic impact of LRP-1 expression in colon cancer and its association with a particular molecular or morphological profile has not been studied to date. In this work, the investigators will study the immunohistochemical and genic expression of LRP-1 in a series of colorectal cancers.

NCT02788669

Conditions

1. Colon Cancer
2. Adenocarcinoma

MeSH:Adenocarcinoma Colonic Neoplasms

HPO:Colon cancer Neoplasm of the colon

- Immunohistochemical analysis on formalin fixed and paraffin embedded tissue will be performed: - qualitative and semi-quantitative evaluation of LRP1 immunoexpression with anti-5A6 and 8G1 antibodies - RER phenotype research (MLH1, MSH2, MSH6 and PMS2 immunohistochemistry) and BRAF V600E immunohistochemistry - Molecular analyzes: - analysis of LRP-1 gene expression on frozen tissue - for selected cases: search for microsatellite instability, search for BRAF V600E, KRAS (exon 2, 3 and 4) and NRAS (exons 2, 3 and 4) mutation on formalin fixed and paraffin embedded tissue Statistical analysis: - Data description: mean and standard deviation for quantitative variables; number and percentage for categorical variables. --- V600E ---

- Immunohistochemical analysis on formalin fixed and paraffin embedded tissue will be performed: - qualitative and semi-quantitative evaluation of LRP1 immunoexpression with anti-5A6 and 8G1 antibodies - RER phenotype research (MLH1, MSH2, MSH6 and PMS2 immunohistochemistry) and BRAF V600E immunohistochemistry - Molecular analyzes: - analysis of LRP-1 gene expression on frozen tissue - for selected cases: search for microsatellite instability, search for BRAF V600E, KRAS (exon 2, 3 and 4) and NRAS (exons 2, 3 and 4) mutation on formalin fixed and paraffin embedded tissue Statistical analysis: - Data description: mean and standard deviation for quantitative variables; number and percentage for categorical variables. --- V600E --- --- V600E ---

Phase I clinical trial to determine the Phase II dose of autologous TIL 1383I TCR gene modified T Cells using a retrovirus. This is a novel National Cancer Institute (NCI) funded investigator initiated therapy for patients with advanced melanoma.

NCT02870244

Conditions

1. Melanoma

Interventions

1. Biological: Escalating Doses

MeSH:Melanoma

HPO:Cutaneous melanoma Melanoma

- Patients with V600E mutations are eligible if they have failed an approved BRAF inhibitor or MEK inhibitor therapy or have refused treatment with an approved BRAF inhibitor or MEK inhibitor. --- V600E ---

This randomized, open-label, two period crossover study will evaluate the effect of food on the pharmacokinetics of a single dose of RO5185426 and the efficacy and safety of continuous administration in patients with BRAF V600E mutation-positive metastatic melanoma. Patients will be randomized to receive in a crossover design single oral doses of RO5185426 with or without food, with a 10-day washout period between doses. Following the crossover periods, patients will receive RO5185426 orally twice daily on a continuous basis until disease progression or unacceptable toxicity occurs.

NCT01264380

Conditions

1. Malignant Melanoma

Interventions

1. Drug: RO5185426
2. Drug: RO5185426
3. Drug: RO5185426

MeSH:Melanoma

HPO:Cutaneous melanoma Melanoma

A Phase I, Randomized, Open-label, Multi-center, Two Period Crossover Study to Investigate the Effect of Food on the Pharmacokinetics of a Single Oral Dose of RO5185426, Followed by Administration of 960 mg RO5185426 Twice Daily to BRAF V600E Positive Metastatic Melanoma Patients. --- V600E ---

A Study of the Effect of Food on the Pharmacokinetics of Single Dose RO5185426 And the Safety And Efficacy of Continuous Administration in Patients With BRAF V600E Mutation-Positive Metastatic Melanoma This randomized, open-label, two period crossover study will evaluate the effect of food on the pharmacokinetics of a single dose of RO5185426 and the efficacy and safety of continuous administration in patients with BRAF V600E mutation-positive metastatic melanoma. --- V600E ---

A Study of the Effect of Food on the Pharmacokinetics of Single Dose RO5185426 And the Safety And Efficacy of Continuous Administration in Patients With BRAF V600E Mutation-Positive Metastatic Melanoma This randomized, open-label, two period crossover study will evaluate the effect of food on the pharmacokinetics of a single dose of RO5185426 and the efficacy and safety of continuous administration in patients with BRAF V600E mutation-positive metastatic melanoma. --- V600E --- --- V600E ---

OS was defined as the time, in months, from the date of the first study drug to the date of death, regardless of the cause of death.. Inclusion Criteria: - Adult patients, >/= 18 years of age - Histologically confirmed metastatic melanoma (Stage IV, American Joint Committee on Cancer) - Positive BRAF V600E mutation result determined by Cobas 4800 BRAF V600 Mutation Test - Previously treated patients must have failed at least one prior treatment regimen; if patients have received prior systemic treatments for metastatic melanoma, the time elapsed from previous therapy must be >/= 28 days; patients must have recovered fully from toxicities of all prior therapy - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 - Evaluable disease (measurable for disease progression according to RECIST criteria) - Adequate hematological, renal and liver function Exclusion Criteria: - Active CNS lesions - History of or known spinal cord compression or carcinomatous meningitis - Anticipated or ongoing administration of anti-cancer therapies other than those administered in this study - Previous malignancy within the past 5 years except for basal or squamous cell carcinoma of the skin, melanoma in-situ and carcinoma in-situ of the cervix - Previous treatment with BRAF inhibitor (sorafenib allowed) or MEK inhibitor - Refractory nausea or vomiting, malabsorption, external biliary shunt, or history of any type of gastrointestinal surgery that would preclude adequate absorption of study drug Inclusion Criteria: - Adult patients, >/= 18 years of age - Histologically confirmed metastatic melanoma (Stage IV, American Joint Committee on Cancer) - Positive BRAF V600E mutation result determined by Cobas 4800 BRAF V600 Mutation Test - Previously treated patients must have failed at least one prior treatment regimen; if patients have received prior systemic treatments for metastatic melanoma, the time elapsed from previous therapy must be >/= 28 days; patients must have recovered fully from toxicities of all prior therapy - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 - Evaluable disease (measurable for disease progression according to RECIST criteria) - Adequate hematological, renal and liver function Exclusion Criteria: - Active CNS lesions - History of or known spinal cord compression or carcinomatous meningitis - Anticipated or ongoing administration of anti-cancer therapies other than those administered in this study - Previous malignancy within the past 5 years except for basal or squamous cell carcinoma of the skin, melanoma in-situ and carcinoma in-situ of the cervix - Previous treatment with BRAF inhibitor (sorafenib allowed) or MEK inhibitor - Refractory nausea or vomiting, malabsorption, external biliary shunt, or history of any type of gastrointestinal surgery that would preclude adequate absorption of study drug Malignant Melanoma Melanoma null --- V600E ---

OS was defined as the time, in months, from the date of the first study drug to the date of death, regardless of the cause of death.. Inclusion Criteria: - Adult patients, >/= 18 years of age - Histologically confirmed metastatic melanoma (Stage IV, American Joint Committee on Cancer) - Positive BRAF V600E mutation result determined by Cobas 4800 BRAF V600 Mutation Test - Previously treated patients must have failed at least one prior treatment regimen; if patients have received prior systemic treatments for metastatic melanoma, the time elapsed from previous therapy must be >/= 28 days; patients must have recovered fully from toxicities of all prior therapy - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 - Evaluable disease (measurable for disease progression according to RECIST criteria) - Adequate hematological, renal and liver function Exclusion Criteria: - Active CNS lesions - History of or known spinal cord compression or carcinomatous meningitis - Anticipated or ongoing administration of anti-cancer therapies other than those administered in this study - Previous malignancy within the past 5 years except for basal or squamous cell carcinoma of the skin, melanoma in-situ and carcinoma in-situ of the cervix - Previous treatment with BRAF inhibitor (sorafenib allowed) or MEK inhibitor - Refractory nausea or vomiting, malabsorption, external biliary shunt, or history of any type of gastrointestinal surgery that would preclude adequate absorption of study drug Inclusion Criteria: - Adult patients, >/= 18 years of age - Histologically confirmed metastatic melanoma (Stage IV, American Joint Committee on Cancer) - Positive BRAF V600E mutation result determined by Cobas 4800 BRAF V600 Mutation Test - Previously treated patients must have failed at least one prior treatment regimen; if patients have received prior systemic treatments for metastatic melanoma, the time elapsed from previous therapy must be >/= 28 days; patients must have recovered fully from toxicities of all prior therapy - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 - Evaluable disease (measurable for disease progression according to RECIST criteria) - Adequate hematological, renal and liver function Exclusion Criteria: - Active CNS lesions - History of or known spinal cord compression or carcinomatous meningitis - Anticipated or ongoing administration of anti-cancer therapies other than those administered in this study - Previous malignancy within the past 5 years except for basal or squamous cell carcinoma of the skin, melanoma in-situ and carcinoma in-situ of the cervix - Previous treatment with BRAF inhibitor (sorafenib allowed) or MEK inhibitor - Refractory nausea or vomiting, malabsorption, external biliary shunt, or history of any type of gastrointestinal surgery that would preclude adequate absorption of study drug Malignant Melanoma Melanoma null --- V600E --- --- V600E ---

This study is designed to assess the efficacy, pharmacokinetics, safety, and tolerability of an oral, twice daily dose of 150 mg GSK2118436 administered to subjects with BRAF V600E or V600K mutation-positive metastatic melanoma to the brain. Subjects in Cohort A will not have received any local brain therapy, and subjects in Cohort B will have received prior local therapy for brain metastases. Subjects will continue on treatment until disease progression, death, or unacceptable adverse event.

NCT01266967

Conditions

1. Melanoma and Brain Metastases

Interventions

1. Drug: GSK2118436

MeSH:Melanoma Neoplasm Metastasis

HPO:Cutaneous melanoma Melanoma

A Study of GSK2118436 in BRAF Mutant Metastatic Melanoma to the Brain This study is designed to assess the efficacy, pharmacokinetics, safety, and tolerability of an oral, twice daily dose of 150 mg GSK2118436 administered to subjects with BRAF V600E or V600K mutation-positive metastatic melanoma to the brain. --- V600E ---

Number of Participants With BRAF V600E Mutation-positive Melanoma With Overall Intracranial Response (OIR), as Assessed by the Investigator. --- V600E ---

Confirmation assessments were to be performed no less than 4 weeks after the criteria for response were initially met and may have been performed at the next protocol scheduled assessment.. Number of Participants With V600E Mutation-positive Melanoma With a Best Overall Response (OR) of CR or PR, as Assessed by the Investigator. --- V600E ---

Confirmation assessments were to be performed no less than 4 weeks after the criteria for response were initially met and may have been performed at the next protocol scheduled assessment.. Duration of Intracranial Response for the Subset of V600E Mutation-positive Participants. --- V600E ---

In addition, the sum must have an absolute increase from nadir of 5 millimeters (mm).. Duration of Overall Response for the Subset of V600E Mutation-positive Participants. --- V600E ---

In addition, the sum must have an absolute increase from nadir of 5 millimeters (mm).. Progression-free Survival in V600E Mutation-positive Participants. --- V600E ---

If a participant received subsequent anti-cancer therapy prior to the date of documented PD/death, the participant was censored at the last adequate assessment and the visit level response was CR (disappearance of all target lesions), PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters [e.g., percent change from Baseline]), or stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.. Overall Survival of V600E Mutation-positive Participants. --- V600E ---

- Histologically confirmed metastatic melanoma (Stage IV), carrying BRAF V600E- or V600K-mutation. --- V600E ---

In Spain, the gastric carcinoma is the 5th most frequent malignant tumor in women and the 6th in men, and represents the 3rd cause of cancer-related deaths amongst women and the 4th amongst men. The average of 5-year survival rate in Spain is under 30%. The main reason of it is that, despite carrying out an adjuvant treatment, more than the 50% will present relapsed disease. Sorafenib has been the first RAF inhibitor, both of RAF-1 and B-rRAF and its b-RAF variant V600E. Moreover, it has shown its ability to inhibit other tyrosin-quinase receptors as VEGFR 2 and 3, c-kit, Flt-3 or PDGFR. Its activity has been clearly proven in clear cell renal carcinoma. The mechanism by which Sorafenib seems to act is not because of the existence of a mutation of RAS or RAF, but because as there is a VHL shortage the HIP produces a VEGF, bFGF or TGF overexpression that produces in turn a hyper-stimulation on the RAF/ERK/MEK pathway. The RAF/MEK/ERK pathway and angiogenesis seem to be clearly involved in the gastric carcinoma tumorigenesis and progression. Because of that, it seems interesting to associate Sorafenib to an oxaliplatin-based chemotherapy, which has shown its effectiveness in relapsed patients after receiving cisplatin-based schemes. Moreover, there is a phase 1 trial confirming the tolerance of the oxaliplatin and Sorafenib association, describing partial responses amongst gastric cancer patients previously treated with cisplatin.

NCT01262482

Conditions

1. Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (Relapsed After a Cisplatin Based Treatment)

Interventions

1. Drug: Oxaliplatin
2. Drug: Sorafenib

MeSH:Adenocarcinoma Esophageal Neoplasms

HPO:Esophageal neoplasm

Sorafenib has been the first RAF inhibitor, both of RAF-1 and B-rRAF and its b-RAF variant V600E. --- V600E ---

This is an open label, single arm phase 1 dose escalation study and phase 2 study of BBI608 in combination with paclitaxel in patients with advanced malignancies. Currently the study is only enrolling patients with thymic carcinoma.

NCT01325441

Conditions

1. Cancer

Interventions

1. Drug: BBI608
2. Drug: Paclitaxel

MeSH:Neoplasms

HPO:Neoplasm

If melanoma is positive for the V600E or V600K BRAF mutation, must have received at least one line of prior therapy with a BRAF-specific inhibitor; either alone or in combination. --- V600E ---

This study will evaluate the safety and tolerability of a personalized live, attenuated, double-deleted Listeria monocytogenes (pLADD) treatment in adults with metastatic colorectal cancer.

NCT03189030

Conditions

1. Colorectal Neoplasms

Interventions

1. Biological: pLADD

MeSH:Colorectal Neoplasms

HPO:Neoplasm of the large intestine

Inclusion Criteria: - metastatic colorectal cancer (mCRC) that is microsatellite stable (MSS) - able to provide adequate tumor tissue from at least 1 accessible tumor site - completed or have developed intolerance to a course of oxaliplatin- or irinotecan-based frontline therapy at Screening - on maintenance standard-of-care chemotherapies or on treatment holiday - Eastern Cooperative Oncology Group (ECOG) 0 or 1 - adequate organ function - progression of disease at the time of Enrollment Exclusion Criteria: - BRAF V600E mutation - known allergy to both penicillin and sulfa drugs - implanted devices that cannot be easily removed - immunodeficiency, immune compromised state or receiving immunosuppressive therapy Inclusion Criteria: - metastatic colorectal cancer (mCRC) that is microsatellite stable (MSS) - able to provide adequate tumor tissue from at least 1 accessible tumor site - completed or have developed intolerance to a course of oxaliplatin- or irinotecan-based frontline therapy at Screening - on maintenance standard-of-care chemotherapies or on treatment holiday - Eastern Cooperative Oncology Group (ECOG) 0 or 1 - adequate organ function - progression of disease at the time of Enrollment Exclusion Criteria: - BRAF V600E mutation - known allergy to both penicillin and sulfa drugs - implanted devices that cannot be easily removed - immunodeficiency, immune compromised state or receiving immunosuppressive therapy Colorectal Neoplasms Colorectal Neoplasms This single arm study is designed to evaluate the safety and tolerability of a personalized treatment in adults with metastatic colorectal cancer by first analyzing the expression of tumor-associated antigens and then treating the patients with a personalized live, attenuated, double-deleted Listeria monocytogenes (pLADD)-based immunotherapy. --- V600E ---

Inclusion Criteria: - metastatic colorectal cancer (mCRC) that is microsatellite stable (MSS) - able to provide adequate tumor tissue from at least 1 accessible tumor site - completed or have developed intolerance to a course of oxaliplatin- or irinotecan-based frontline therapy at Screening - on maintenance standard-of-care chemotherapies or on treatment holiday - Eastern Cooperative Oncology Group (ECOG) 0 or 1 - adequate organ function - progression of disease at the time of Enrollment Exclusion Criteria: - BRAF V600E mutation - known allergy to both penicillin and sulfa drugs - implanted devices that cannot be easily removed - immunodeficiency, immune compromised state or receiving immunosuppressive therapy Inclusion Criteria: - metastatic colorectal cancer (mCRC) that is microsatellite stable (MSS) - able to provide adequate tumor tissue from at least 1 accessible tumor site - completed or have developed intolerance to a course of oxaliplatin- or irinotecan-based frontline therapy at Screening - on maintenance standard-of-care chemotherapies or on treatment holiday - Eastern Cooperative Oncology Group (ECOG) 0 or 1 - adequate organ function - progression of disease at the time of Enrollment Exclusion Criteria: - BRAF V600E mutation - known allergy to both penicillin and sulfa drugs - implanted devices that cannot be easily removed - immunodeficiency, immune compromised state or receiving immunosuppressive therapy Colorectal Neoplasms Colorectal Neoplasms This single arm study is designed to evaluate the safety and tolerability of a personalized treatment in adults with metastatic colorectal cancer by first analyzing the expression of tumor-associated antigens and then treating the patients with a personalized live, attenuated, double-deleted Listeria monocytogenes (pLADD)-based immunotherapy. --- V600E --- --- V600E ---

This phase II trial investigates how well adding hydroxychloroquine to the standard treatment of dabrafenib and trametinib works to overcome resistance and delay disease progression in treating patients with stage IIIC or IV BRAF V600E/K melanoma. Hydroxychloroquine may cause cell death in tumor cells that rely on a process called "autophagy" for survival. Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving hydroxychloroquine together with dabrafenib and trametinib may work better than dabrafenib and trametinib alone to shrink and stabilize the cancer.

NCT04527549

Conditions

1. Clinical Stage IV Cutaneous Melanoma AJCC v8
2. Locally Advanced Melanoma
3. Pathologic Stage IIIC Cutaneous Melanoma AJCC v8
4. Pathologic Stage IV Cutaneous Melanoma AJCC v8
5. Unresectable Melanoma

Interventions

1. Drug: Dabrafenib Mesylate
2. Drug: Hydroxychloroquine Sulfate
3. Drug: Placebo Administration
4. Drug: Trametinib Dimethyl Sulfoxide

MeSH:Melanoma Skin Neoplasms

HPO:Cutaneous melanoma Melanoma Neoplasm of the skin

The BAMM2 (BRAF, Autophagy, MEK Inhibition in Melanoma) Study: A Randomized Double Blind Phase II Study of Dabrafenib and Trametinib With or Without Hydroxychloroquine in Advanced BRAF V600E/K Melanoma. --- V600E ---

Testing Dabrafenib and Trametinib With or Without Hydroxychloroquine in Stage IIIC or IV BRAF V600E/K Melanoma This phase II trial investigates how well adding hydroxychloroquine to the standard treatment of dabrafenib and trametinib works to overcome resistance and delay disease progression in treating patients with stage IIIC or IV BRAF V600E/K melanoma. --- V600E ---

Testing Dabrafenib and Trametinib With or Without Hydroxychloroquine in Stage IIIC or IV BRAF V600E/K Melanoma This phase II trial investigates how well adding hydroxychloroquine to the standard treatment of dabrafenib and trametinib works to overcome resistance and delay disease progression in treating patients with stage IIIC or IV BRAF V600E/K melanoma. --- V600E --- --- V600E ---

Will be estimated by treatment arm.. Inclusion Criteria: - Patient must have locally advanced unresectable stage IIIC or stage IV melanoma - Patient must have BRAF V600E or BRAF V600K tumor genotype based on a Clinical Laboratory Improvement Act (CLIA) approved assay - Patient must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. --- V600E ---

phenytoin, carbamazepine, phenobarbital, primidone or oxcarbazepine) within 4 weeks prior to randomization - Patient must not have a current use of a prohibited medication Inclusion Criteria: - Patient must have locally advanced unresectable stage IIIC or stage IV melanoma - Patient must have BRAF V600E or BRAF V600K tumor genotype based on a Clinical Laboratory Improvement Act (CLIA) approved assay - Patient must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. --- V600E ---

A Phase II study of the BRAF inhibitor Encorafenib in combination with the MEK inhibitor Binimetinib in Patients with BRAFV600E-mutant metastatic Non-small Cell Lung Cancer

NCT04526782

Conditions

1. Non Small Cell Lung Cancer
2. BRAF V600E

Interventions

1. Drug: Encorafenib 75 MG
2. Drug: Binimetinib 15 MG
3. Drug: Docetaxel

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

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

Non Small Cell Lung Cancer BRAF V600E Lung Neoplasms Carcinoma, Non-Small-Cell Lung null --- V600E ---

To enhance the diagnosis of unclassifiable, non-CLL B-LPDs using next-generation sequencing technology.

NCT03344809

Conditions

1. Lymphoma

MeSH:Lymphoproliferative Disorders

HPO:Lymphoproliferative disorder

While some of these mutations, such as the BRAF V600E mutation in Hairy Cell Leukaemia (HCL)2, are now accepted as disease defining mutations, others such as MYD88 and NOTCH1/2 mutations are found in more than one subtype of B-LPD3. --- V600E ---

The purpose of this phase 2 study is to evaluate the efficacy and safety of NIR178 in combination with PDR001 in multiple solid tumors and diffuse large B-cell lymphoma (DLBCL) and further explore schedule variations of NIR178 to optimize immune activation through inhibition of A2aR.

NCT03207867

Conditions

1. NSCLC, Non Small Cell Lung Cancer
2. RCC, Renal Cell Cancer
3. Pancreatic Cancer
4. Urothelial Cancer
5. Head and Neck Cancer
6. DLBCL, Diffused Large B Cell Lymphoma
7. MSS, Microsatellite Stable Colon Cancer
8. TNBC, Triple Negative Breast Cancer
9. Melanoma
10. mCRPC, Metastatic Castration Resistant Prostate Cancer

Interventions

1. Drug: NIR178
2. Drug: PDR001

MeSH:Lymphoma Lymphoma, Non-Hodgkin Triple Negative Breast Neoplasms Carcinoma, Renal Cell

HPO:Clear cell renal cell carcinoma Lymphoma Non-Hodgkin lymphoma Papillary renal cell carcinoma Renal cell carcinoma

Patients with melanoma: BRAF V600E wild type patients: must have received anti-PD-1/PD-L1 single agent, or in combination with anti-CTLA-4 therapy BRAF V600E mutant patients: must have received prior anti-PD-1/PD-L1 single-agent, or in combination with anti-CTLA-4 therapy. --- V600E ---

Patients with melanoma: BRAF V600E wild type patients: must have received anti-PD-1/PD-L1 single agent, or in combination with anti-CTLA-4 therapy BRAF V600E mutant patients: must have received prior anti-PD-1/PD-L1 single-agent, or in combination with anti-CTLA-4 therapy. --- V600E --- --- V600E ---

In addition, subjects must have received prior BRAF V600E inhibitor therapy, either single-agent or in combination with a MEK inhibitor Patients with Metastatic Castration Resistant Prostate Cancer (mCRPC): - Of the 1-3 prior lines of therapy, patients must have received and failed at least one line of treatment after emergence of castration resistant disease - Patients must not have received prior immunotherapy (previous immune checkpoint inhibitors; single agent and/or combination therapy with anti-CTLA-4, anti-PD-1, anti-PD-L1), except for NSCLC patients enrolled in part 3 and Japanese safety run-in part. --- V600E ---

The purpose of this study is to develop a new drug treatment to reverse tumor resistance to radioiodine in BRAF mutant tumors so that radioiodine can be given to shrink tumors. This study is also being done to find out the highest doses of copanlisib and vemurafenib that, when given in combination, do not cause serious side effects, and whether the study treatment will make radioiodine therapy work better in patients with BRAF-mutant thyroid cancers.

NCT04462471

Conditions

1. Thyroid Carcinoma
2. Thyroid Cancer
3. Thyroid Cancer, Follicular
4. Thyroid Cancer (Follicular Cell)
5. Thyroid Cancer, Papillary
6. BRAF V600E Mutation Positive

Interventions

1. Diagnostic Test: I-124 PET/CT lesion dosimetry
2. Drug: Vemurafenib
3. Drug: Copanlisib

MeSH:Thyroid Neoplasms Thyroid Cancer, Papillary Thyroid Diseases

HPO:Abnormality of the thyroid gland Neoplasm of the thyroid gland Thyroid adenoma Thyroid carcinoma Thyroid follicular adenoma

Thyroid Carcinoma Thyroid Cancer Thyroid Cancer, Follicular Thyroid Cancer (Follicular Cell) Thyroid Cancer, Papillary BRAF V600E Mutation Positive Thyroid Neoplasms Thyroid Cancer, Papillary Thyroid Diseases null --- V600E ---

The purpose of the study is to determine safety and tolerability of the combination of talimogene laherparepvec in combination with dabrafenib and trametinib in BRAF mutated advanced melanoma.

NCT03088176

Conditions

1. Melanoma
2. BRAF Gene Mutation

Interventions

1. Drug: Talimogene Laherparepvec 1 Million Pfu/Ml Inj,Susp,1Ml,Vil
2. Drug: Talimogene Laherparep 100 Mil Pfu/Ml 1Ml
3. Drug: Dabrafenib
4. Drug: Trametinib

MeSH:Melanoma

HPO:Cutaneous melanoma Melanoma

Primary or recurrent Stage IIIB to IVM1c melanoma for whom surgery is not recommended 3. Activating BRAF mutation (limited to V600E or V600K mutations if being treated first-line, but can include any well-defined BRAF mutation after failure of prior immunotherapy) 4. Measurable disease defined as follows: At least one melanoma lesion that can be accurately and serially measured in one dimension and for which the longest diameter is ≥10 mm as measured by calipers, CT scan, or MRI. --- V600E ---

BRF113683 is a Phase III, randomized, open-label study comparing the efficacy, safety, and tolerability of GSK2118436 to dacarbazine (DTIC), in subjects with BRAF mutant advanced (Stage III) or metastatic (Stage IV) melanoma. Subjects will be randomized to receive 150 mg of GSK2118436 twice daily or 1000 mg/m2 DTIC every 3 weeks and continue on treatment until disease progression, death, or unacceptable adverse event. Subjects who progress on DTIC will be allowed to crossover to an optional extension arm of the study to receive GSK2118436.

NCT01227889

Conditions

1. Cancer

Interventions

1. Drug: GSK2118436
2. Drug: Dacarbazine (DTIC)

MeSH:Melanoma

HPO:Cutaneous melanoma Melanoma

The number of participants with non-melanoma skin lessions was assessed from the time of Screening until study completion or discontinuation from the study for any reason.. Agreement Rate for V600E Mutation Validation of the BRAF Mutation Assay. --- V600E ---

Multiple specimen per participant were analyzed.. Inclusion Criteria: - Adults at least 18 years of age - Has advanced (unresectable Stage III) or metastatic (Stage IV) melanoma that is BRAF mutation positive (V600E) - Is treatment naive for advanced (unresectable) or metastatic melanoma, with the exception of Interleukin 2 (IL-2) which is allowed. --- V600E ---

- Certain cardiac abnormalities Inclusion Criteria: - Adults at least 18 years of age - Has advanced (unresectable Stage III) or metastatic (Stage IV) melanoma that is BRAF mutation positive (V600E) - Is treatment naive for advanced (unresectable) or metastatic melanoma, with the exception of Interleukin 2 (IL-2) which is allowed. --- V600E ---

Background: - Papillary thyroid cancer (PTC) often spreads to lymph nodes in the neck. This can be hard to detect. People often have lymph nodes removed anyway, and researchers want to study if this is a good idea. Objective: - To compare the effectiveness of removing lymph nodes in the neck that show no evidence of cancer along with the thyroid, or removing only the thyroid. Eligibility: - Adults age 18 and older with PTC or thyroid nodules suspicious for PTC, with no evidence that the disease has spread in the body. Design: - Participants will be screened with medical history, physical exam, blood tests, scans, and x-rays. - Participants will: - Answer questions. They may have a tumor biopsy. - Have a flexible laryngoscopy. A small tube will pass through the nose to the vocal cords. - Group 1: have surgery to remove the thyroid gland only. Lymph nodes in the neck will be removed if the cancer has spread. - Group 2: have surgery to remove the thyroid and lymph nodes in the neck. - At all post-surgery visits, participants will answer questions and have blood drawn. In addition: - 1 day: laryngoscopy. - 2 weeks: possible laryngoscopy. - 3 months: ultrasound of the thyroid and neck. - Discuss whether to try hormone treatment and/or radioactive iodine. - Possible diagnostic whole body radioiodine scan (WBS). Participants will swallow a capsule or liquid and lie under a camera. - 6 months: ultrasound and maybe laryngoscopy. - 1 year: diagnostic WBS and ultrasound. Participants may get thyroid stimulating hormone. - Participants will have annual follow-up visits for 10 years. They will have a physical exam, blood drawn, scans, and may complete a questionnaire.

NCT02408887

Conditions

1. Low-risk Papillary Thyroid Cancer
2. Endocrine Malignancy
3. Thyroid Cancer

Interventions

1. Procedure: Total Thyroidectomy (TT)
2. Procedure: Prophylactic central neck lymph nodedissection (pCND)

MeSH:Thyroid Neoplasms Thyroid Cancer, Papillary Thyroid Diseases

HPO:Abnormality of the thyroid gland Neoplasm of the thyroid gland Thyroid adenoma Thyroid carcinoma Thyroid follicular adenoma

The impact of BRAF V600E mutation status on lymph node metastasis. --- V600E ---

Correlation between BRAF V600E of tumor and median amount of time before disease progression. --- V600E ---

but less than or equal to 4 cm measured in greatest dimension and confirmed by the Laboratory of Pathology, NCI or confirmed by the pathology laboratory of the enrolling institution: - Indeterminate thyroid biopsy per Bethesda System for reporting thyroid cytopathology with BRAF V600E mutation or RET/PTC rearrangement - Cytologically or histologically suspicious or confirmed PTC per Bethesda System for reporting thyroid cytopathology. --- V600E ---

but less than or equal to 4 cm. in size with either: - inconclusive thyroid cytology positive for BRAF V600E mutation or RET/PTC rearrangement or - cytologically suspicious for or consistent with PTC - Absence of extrathyroidal extension or lymphadenopathy suggesting metastatic PTC on physical examination and neck ultrasound. --- V600E ---

This is an open-label, multi-center, clinical phase II study to explore the correlation of the genetic make-up of the treated tumor before start of therapy and to correlate clinical response at 8 weeks as well as metabolic response at 2 and 8 weeks with genetic features of the tumor. It will be conducted as a rationale optimization of targeted therapy in BRAF naïve and pretreated patients. Prerequisite for all patients is the availability of tumor sample at start of treatment in order to determine the underlying driver mutation (BRAF mutational status) as well as molecular composition by next generation sequencing (NGS) and assessable lesions for biopsy at week 2. Melanoma patients in stage III (non-resectable) and stage IV are sorted into Cohort A or B according to their previous BRAF-treatment and treated with dabrafenib and trametinib (cohort A and B)

NCT02410863

Conditions

1. Malignant Melanoma

Interventions

1. Drug: Dabrafenib
2. Drug: Trametinib

MeSH:Melanoma

HPO:Cutaneous melanoma Melanoma

Prerequisite for all patients is the availability of tumor sample at start of treatment in order to determine the underlying driver mutation (BRAF mutational status) as well as molecular composition by next generation sequencing (NGS) and assessable lesions for biopsy at week 2. Melanoma patients in stage III (non-resectable) and stage IV are sorted into Cohort A or B according to their previous BRAF-treatment and treated with dabrafenib and trametinib (cohort A and B) Correlation of clinical response at week 8 of targeted therapy with molecular results of the biopsies.. To broaden the understanding of molecular characterization of the melanoma in correlation to the clinical response (defined as partial or complete response according to RECIST) at week 8 of targeted therapy in different pre-treated patients with advanced/metastatic BRAF V600E/K mutation-positive cutaneous melanoma.. Correlation of the tumor´s molecular composition to metabolic responses. --- V600E ---

3. Histologically confirmed cutaneous melanoma that is either Stage IIIc (unresectable) or Stage IV (metastatic), and determined to be BRAF V600E/K mutation-positive by the central laboratory. --- V600E ---

This is a single arm open label, multicenter, non randomized, access study of trametinib for subjects with histologically confirmed cutaneous melanoma with a BRAF V600E/K positive mutation that is either advanced unresectable (stage IIIc) or distant metastatic (stage IV). Trametinib may be given as monotherapy or in combination since first line metastatic melanoma as per inclusion criteria. Subjects who received prior BRAF inhibitor may be included if they have not progressed under such treatment or if they have presented limited progression as per eligibility criteria. It is estimated that between 250 and 400 subjects with histologically confirmed cutaneous melanoma with a BRAF V600E/K positive mutation that is either advanced unresectable (stage IIIc) or distant metastatic (stage IV) will be enrolled.

NCT02416232

Conditions

1. Melanoma

Interventions

1. Drug: Trametinib
2. Drug: Dabrafenib

MeSH:Melanoma

HPO:Cutaneous melanoma Melanoma

An Open Label Non Randomized Access Study of Trametinib for Patients With Advanced Unresectable (Stage IIIc) or Distant Metastatic (Stage IV) BRAF V600E/K Mutation Positive Cutaneous Melanoma. --- V600E ---

Access Study of Trametinib for Subjects With Advanced Unresectable (Stage IIIc) or Distant Metastatic (Stage IV) BRAF V600E/K Mutation Positive Cutaneous Melanoma This is a single arm open label, multicenter, non randomized, access study of trametinib for subjects with histologically confirmed cutaneous melanoma with a BRAF V600E/K positive mutation that is either advanced unresectable (stage IIIc) or distant metastatic (stage IV). --- V600E ---

Access Study of Trametinib for Subjects With Advanced Unresectable (Stage IIIc) or Distant Metastatic (Stage IV) BRAF V600E/K Mutation Positive Cutaneous Melanoma This is a single arm open label, multicenter, non randomized, access study of trametinib for subjects with histologically confirmed cutaneous melanoma with a BRAF V600E/K positive mutation that is either advanced unresectable (stage IIIc) or distant metastatic (stage IV). --- V600E --- --- V600E ---

It is estimated that between 250 and 400 subjects with histologically confirmed cutaneous melanoma with a BRAF V600E/K positive mutation that is either advanced unresectable (stage IIIc) or distant metastatic (stage IV) will be enrolled. --- V600E ---

- Has histologically confirmed cutaneous melanoma BRAF V600E/K positive mutation either unresectable (stage IIIc) or distant metastatic (stage IV). - Is not eligible for enrolment in any other ongoing relevant hypothesis testing clinical study for metastatic melanoma or, if eligible, is so geographically distant from a participating site that attending frequent clinic visits is not feasible. --- V600E ---

Rationale: The combination of ipilimumab and nivolumab induces relatively high response rates and promising response depth in late stage melanoma. Nevertheless, it takes time till responses occur and still a significant number of patients do not benefit from treatment, due to rapid progressive disease or resistance to therapy. In contrast to immunotherapies targeted therapies (BRAF or MEK inhibitors), can induce faster and higher response rates, but often of shorter duration, even when combined. Initial attempts of combining vemurafenib or dabrafenib + trametinib with ipilimumab failed due to toxicity. Patients with elevated levels of serum LDH are less likely to respond to immunotherapy compared to patients with normal LDH levels. This does not mean that such patients do not benefit at all from immunotherapy. This raises the question, whether response rates upon immunotherapy can be improved by upfront reduction of tumor burden and normalization of LDH. The investigators postulate that induction therapy with combined BRAF+MEK inhibition, and subsequent LDH normalization, can improve response rates to the rates seen in LDH normal patients. To address this question the investigators have setup a randomized phase 2 trial in metastatic melanoma patients with elevated serum LDH comparing the response rates upon ipilimumab + nivolumab versus ipilimumab + nivolumab preceded by 6 weeks of vemurafenib + cobimetinib induction. Furthermore, less than half of the patients treated with the combination of ipilimumab and nivolumab received maintenance nivolumab, and approximately 40% of all patients discontinued treatment for toxicity. In 70% of patients responses were ongoing despite discontinuation of treatment due to toxicity. This raises the question, to what extent does maintenance therapy add clinical benefit to an ongoing immune response. Preclinical data indicate even that continuous restimulation of T cells can result in activation induced non-responsiveness (anergy). Therefore, a secondary objective of this trial will be, to test a response-driven nivolumab scheme Objectives: Primary Objective • To compare efficacy of induction vemurafenib + cobimetinib followed by ipilimumab + nivolumab (Arm A) versus upfront ipilimumab + nivolumab treatment (Arm B). Secondary Objectives - To describe duration of response and overall survival induced by vemurafenib + cobimetinib followed by the combination of ipilimumab + nivolumab (Arm A) as compared to ipilimumab + nivolumab (Arm B) - To describe the rate and quality of toxicity observed in the two study arms - To describe the rate of ongoing responses upon response-driven flat dose (240mg q2w or 480mg q4w) nivolumab maintenance - To determine the immune-activating capacity of induction therapy with vemurafenib + cobimetinib followed by the combination of ipilimumab + nivolumab. - To evaluate the changes in systemic immune competence Study design: This is a two-arm phase 2 study consisting of 200 BRAFV600E/K mutation-positive late-stage melanoma patients with an elevated baseline LDH level (> ULN, < 3xULN) randomized 1:1 (stratified according to LDH) to receive either vemurafenib + cobimetinib directly followed by ipilimumab + nivolumab (Arm A) or standard first line ipilimumab + nivolumab (Arm B). Subsequently, patients in both arms will receive flat dose (240mg q2w or 480mg q4w) nivolumab maintenance in a response-driven manner. Study population: Stage IV, or unresectable stage III, BRAFV600E/K mutation positive melanoma patients, naïve for BRAF/MEK, PD-1/PD-L1 or CTLA-4 targeting therapy, 18 years and older. Intervention: Patients will be randomized 1:1 to receive either 6 weeks vemurafenib 960 mg bid + cobimetinib 60 mg QD 21-day on, 7-day off (21/7) schedule, directly followed by 4 courses of ipilimumab 3mg/kg q3wk + nivolumab 1mg/kg q3wk (Arm A) or first line standard 4 courses of ipilimumab 3mg/kg q3wk + nivolumab 1mg/kg q3wk (Arm B). Subsequently, patients in both arms will receive nivolumab maintenance flat dose (240mg q2w or 480mg q4w) in a response-driven manner according to their response at week 18. Main study parameters/endpoints: Primary Endpoints • Compare the best overall response rate (BORR) according to RECIST 1.1 of both arms at week 18 from start of treatment. Secondary Endpoints - Progression-free survival (PFS) according to RECIST 1.1 - Overall survival (OS) - Percentage of grade 3/4 toxicities according to CTCv4.03 - Percentage of ongoing response, percentage of patients requiring re-induction, response percentage upon re-induction - Changes in tumor-specific T cell responses

NCT02968303

Conditions

1. Melanoma, Malignant, of Soft Parts

Interventions

1. Drug: Vemurafenib and Cobimetinib

MeSH:Melanoma Sarcoma, Clear Cell

HPO:Cutaneous melanoma Melanoma

Phase 2 Study With COmbination of Vemurafenib With Cobimetinib in B-RAF V600E/K Mutated Melanoma Patients to Normalize LDH and Optimize Nivolumab and Ipilimumab therapY. --- V600E ---

Inclusion Criteria: - Adults 18 years and older - World Health Organization (WHO) Performance Status 0-2 - Histologically or cytologically confirmed Stage IV, or unresectable stage III, BRAF V600E/K mutated melanoma - Measurable disease according to RECIST 1.1 - Signed and dated informed consent form - No prior immunotherapy targeting CTLA-4, PD-1 or PD-L1 - No prior BRAFi and/ or MEKi therapy - No immunosuppressive medications - Screening laboratory values must meet the following criteria and should be obtained within 10 days prior to randomization: - WBC ≥ 2.0x109/L, Neutrophils ≥ 1.0x109/L, Platelets ≥ 100 x109/L, Hemoglobin ≥ 5.0 mmol/L - Creatinine ≤ 2x ULN or creatinine clearance (CrCl) ≥ 40 ml/min - AST, ALT ≤ 3.0 x ULN (≤5 x ULN for patients with liver metastases) - Bilirubin ≤ 2.0 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL ) - LDH > ULN, < 5.0 x ULN - No symptomatic brain metastases (asysmptomatic brain metastases, accidentally found during screening can be included) - No leptomeningeal metastases - No active autoimmune disease requiring systemic treatment in the past 3 months or a documented history of autoimmune disease, or history of syndrome that required systemic steroids, at daily dose of ≥10mg prednisone or equivalent, or immunosuppressive medications. --- V600E ---

- No underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity determination or adverse events Inclusion Criteria: - Adults 18 years and older - World Health Organization (WHO) Performance Status 0-2 - Histologically or cytologically confirmed Stage IV, or unresectable stage III, BRAF V600E/K mutated melanoma - Measurable disease according to RECIST 1.1 - Signed and dated informed consent form - No prior immunotherapy targeting CTLA-4, PD-1 or PD-L1 - No prior BRAFi and/ or MEKi therapy - No immunosuppressive medications - Screening laboratory values must meet the following criteria and should be obtained within 10 days prior to randomization: - WBC ≥ 2.0x109/L, Neutrophils ≥ 1.0x109/L, Platelets ≥ 100 x109/L, Hemoglobin ≥ 5.0 mmol/L - Creatinine ≤ 2x ULN or creatinine clearance (CrCl) ≥ 40 ml/min - AST, ALT ≤ 3.0 x ULN (≤5 x ULN for patients with liver metastases) - Bilirubin ≤ 2.0 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL ) - LDH > ULN, < 5.0 x ULN - No symptomatic brain metastases (asysmptomatic brain metastases, accidentally found during screening can be included) - No leptomeningeal metastases - No active autoimmune disease requiring systemic treatment in the past 3 months or a documented history of autoimmune disease, or history of syndrome that required systemic steroids, at daily dose of ≥10mg prednisone or equivalent, or immunosuppressive medications. --- V600E ---

This open-label single arm study will assess the efficacy, safety and tolerability of Vemurafenib in previously treated patients with metastatic melanoma. Patients will receive oral Vemurafenib [RG7204; PLEXXIKON: PLX4032] at a dose of 960 mg b.i.d. continuously until disease progression or withdrawal from study and will be assessed at regular intervals for tumour response and tolerability. Target sample size is <100 patients.

NCT00949702

Conditions

1. Malignant Melanoma

Interventions

1. Drug: vemurafenib

MeSH:Melanoma

HPO:Cutaneous melanoma Melanoma

DTIC, temozolomide, etc.) - BRAF V600E positive mutation (by Roche CoDx BRAF mutation assay) - measurable disease by RECIST criteria - negative pregnancy test and, for fertile men and women, effective contraception during treatment and for 6 months after completion Exclusion Criteria: - active CNS metastases on CT/MRI within 28 days prior to enrollment - history of or known carcinomatous meningitis - previous treatment with BRAF (sorafenib allowed) or MEK inhibitor - cardiac dysrhythmias >2 NCI CTCAE or treatment with drugs with dysrhythmic potential - uncontrolled hypertension(>150/100mmHg) despite optimal medical therapy - infectious disease including HIV, HBV and HCV Inclusion Criteria: - adult patients >/=18 years of age - histologically confirmed metastatic melanoma (Stage IV, AJCC) - patients must have completed and failed at least one prior standard of care regimen (e.g. --- V600E ---

DTIC, temozolomide, etc.) - BRAF V600E positive mutation (by Roche CoDx BRAF mutation assay) - measurable disease by RECIST criteria - negative pregnancy test and, for fertile men and women, effective contraception during treatment and for 6 months after completion Exclusion Criteria: - active CNS metastases on CT/MRI within 28 days prior to enrollment - history of or known carcinomatous meningitis - previous treatment with BRAF (sorafenib allowed) or MEK inhibitor - cardiac dysrhythmias >2 NCI CTCAE or treatment with drugs with dysrhythmic potential - uncontrolled hypertension(>150/100mmHg) despite optimal medical therapy - infectious disease including HIV, HBV and HCV Malignant Melanoma Melanoma null --- V600E ---

The purpose of this study is to evaluate the safety, pharmacokinetics, pharmacodynamics and maximum tolerated dose of TAK-733 in patients with advanced, nonhematologic tumors. The expansion stage of the study will evaluate evidence of antitumor activity of TAK-733 in patients with advanced metastatic melanoma.

NCT00948467

Conditions

1. Advanced Non-hematologic Malignancies
2. Advanced Metastatic Melanoma

Interventions

1. Drug: TAK-733

MeSH:Melanoma Neoplasms

HPO:Cutaneous melanoma Melanoma Neoplasm

- Melanoma patients should have the V600E BRAF mutation status of their tumor documented, if available, and tumor tissue must be provided for confirmatory genotyping by a central laboratory. --- V600E ---

Uveal melanoma is the most common primary intra-ocular malignancy in adults with an incidence of 0.6 - 0.7 per 100,000 per year. Prognosis of metastatic uveal melanoma is poor. In retrospective analyses a median survival time after detection of metastases of 5 months (Flaherty et al, 1998) and 7 months (Kath et al, 1993) was reported. For patients receiving no treatment reported median survival was 2.0 months compared with 5.2 months for those receiving treatment for metastases (Gragoudas et al, 1991). Up to now there is no established treatment of metastatic uveal melanoma. Some therapeutic approaches with locoregional treatment or systemic chemotherapy have been undertaken: In case of metastatic disease which is confined to the liver in about 85% of patients with uveal melanoma surgical resection led to a median survival of 14 months (Mariani et al, 2009) or 19 months and a 5-year survival rate of 22% in a selected patient population (Adam et al, 2006). As locoregional treatment option treatment with fotemustine via direct intra-arterial hepatic infusion was investigated and led to a median survival of 15 months (Peters et al, 2006). This was not a randomized trial, but a report on 101 consecutive treated patients. Additional debulking surgery was performed whenever feasible. A randomized phase III trial comparing intra-arterial hepatic fotemustine administration with intravenous systemic fotemustine and overall survival as primary endpoint is still ongoing (EORTC 18021). Thus, no systemic chemotherapy is approved for metastatic uveal melanoma. Although no specific genes have been linked to the pathogenesis of uveal melanoma, preclinical studies suggest potential benefit of inhibitors of Bcl-2, ubiquitin-proteasome, histone deactylase, mitogen-activated protein kinase and phosphatidylinositol-3-kinase-AKT pathways, and receptor tyrosine kinases. Thus, sorafenib as inhibitor of b-Raf and Raf-1 (c-Raf or c-Raf-1), pro-angiogenic vascular endothelial growth factor receptor (VEGFR), and platelet-derived growth factor receptor (PDGFR) may potentially lead to a benefit for patients with metastatic uveal melanoma in terms of disease control and prolongation of survival.

NCT01377025

Conditions

1. Uveal Melanoma

Interventions

1. Drug: Placebo
2. Drug: Sorafenib
3. Drug: Sorafenib

MeSH:Melanoma Uveal Neoplasms

HPO:Cutaneous melanoma Melanoma

Thus, sorafenib as oral multi-kinase inhibitor that targets the Raf/MEK/ERK signaling pathway (CRAF, BRAF, V600E BRAF) in the cell and receptor tyrosine kinases (RTKs) such as VEGFR-2, VEGFR-3, and PDGFR-ß involved in tumor cell proliferation and angiogenesis may potentially lead to a benefit for patients with metastatic uveal melanoma in terms of disease control and prolongation of survival. --- V600E ---

The purpose of CTO-IUSCC-0730 study is to assess the clinical efficacy of LY3214996 in combination with abemaciclib at the recommended phase 2 dose of LY3214996 200 mg orally daily and abemaciclib 150 mg orally twice daily. Patients will be treated until evidence of disease progression, non-compliance with study protocol, unacceptable major toxicity, at subject's own request for withdrawal, or if the study closes for any reason.

NCT04534283

Conditions

1. Cancer
2. Cancer Metastatic
3. BRAF V600E
4. MEK1 Gene Mutation
5. MEK2 Gene Mutation
6. ERK Mutation
7. RAF1 Gene Mutation

Interventions

1. Drug: Abemaciclib
2. Drug: LY3214996

i. Patients with NSCLC that harbor BRAF V600E treated with prior RAF and/or MEK inhibition therapy will be excluded. --- V600E ---

Patients with tumor types other than NSCLC that harbor BRAF V600E mutations who have been treated and progressed on prior BRAF and/or MEK inhibition will be included. --- V600E ---

Cancer Cancer Metastatic BRAF V600E MEK1 Gene Mutation MEK2 Gene Mutation ERK Mutation RAF1 Gene Mutation null --- V600E ---

The purpose of this study is to evaluate the safety and efficacy of dabrafenib in combination with trametinib in Chinese patients with BRAF V600E mutation-positive metastatic Non-Small Cell Lung Cancer. The general study design has been discussed and agreed with Chinese Health Authority and is applying a similar design used for global pivotal phase II study (BRF113928).

NCT04452877

Conditions

1. Carcinoma, Non-Small-Cell Lung

Interventions

1. Drug: Dabrafenib
2. Drug: Trametinib

MeSH:Carcinoma, Non-Small-Cell Lung

HPO:Non-small cell lung carcinoma

An Open-Label, Single-arm Study to Evaluate the Safety and Efficacy of Dabrafenib in Combination With Trametinib in Chinese Patients With BRAF V600E Mutation-Positive Metastatic Non-Small Cell Lung Cancer. --- V600E ---

A Study of Dabrafenib in Combination With Trametinib in Chinese Patients With BRAF V600E Mutant Metastatic NSCLC The purpose of this study is to evaluate the safety and efficacy of dabrafenib in combination with trametinib in Chinese patients with BRAF V600E mutation-positive metastatic Non-Small Cell Lung Cancer. --- V600E ---

A Study of Dabrafenib in Combination With Trametinib in Chinese Patients With BRAF V600E Mutant Metastatic NSCLC The purpose of this study is to evaluate the safety and efficacy of dabrafenib in combination with trametinib in Chinese patients with BRAF V600E mutation-positive metastatic Non-Small Cell Lung Cancer. --- V600E --- --- V600E ---

Incidence of Adverse Events and Serious Adverse events, including abnormal laboratory values or test results.. Inclusion Criteria: - Histologically or cytologically confirmed diagnosis of Stage IV NSCLC (according to AJCC 8th edition) that is BRAF V600E mutation-positive by local test result from a qualified assay (NMPA and/or MOH-approved) - Previously treated or untreated for metastatic NSCLC: 1. Subjects previously treated should have received no more than 3 prior systemic therapies for metastatic disease, including one prior platinum based chemotherapy, and should have documented disease progression on a prior treatment regimen (i.e. --- V600E ---

The amount of time a patient must use a condom for 16 weeks post treatment discontinuation - Subjects with active Hepatitis B infection (HbsAg positive) - Subjects with positive test for hepatitis C ribonucleic acid (HCV RNA) - Concurrent participation in other clinical trials using experimental therapies Inclusion Criteria: - Histologically or cytologically confirmed diagnosis of Stage IV NSCLC (according to AJCC 8th edition) that is BRAF V600E mutation-positive by local test result from a qualified assay (NMPA and/or MOH-approved) - Previously treated or untreated for metastatic NSCLC: 1. Subjects previously treated should have received no more than 3 prior systemic therapies for metastatic disease, including one prior platinum based chemotherapy, and should have documented disease progression on a prior treatment regimen (i.e. --- V600E ---

The amount of time a patient must use a condom for 16 weeks post treatment discontinuation - Subjects with active Hepatitis B infection (HbsAg positive) - Subjects with positive test for hepatitis C ribonucleic acid (HCV RNA) - Concurrent participation in other clinical trials using experimental therapies Carcinoma, Non-Small-Cell Lung Carcinoma, Non-Small-Cell Lung This is a single arm, open label, multicenter phase II study evaluating the efficacy and safety of dabrafenib in combination with trametinib in Chinese subjects with BRAF V600E mutation positive AJCC v8 stage IV Non-Small Cell Lung Cancer. --- V600E ---

Subjects with stage IV BRAF V600E mutant Non-Small Cell Lung Cancer confirmed by local qualified assay (approved by China health authorities) will be enrolled in this study. --- V600E ---

Central confirmation testing for BRAF V600E will be performed. --- V600E ---

This is a multicenter, 2-arm open-label, randomized comparative phase II study. The objective of this trial is to prospectively evaluate whether a sequential approach with an induction period of 12 weeks with encorafenib + binimetinib followed by combination immunotherapy with nivolumab + ipilimumab improves progression free survival compared to combination immunotherapy nivolumab + ipilimumab alone in patients with BRAF V600 mutation-positive unresectable or metastatic melanoma.

NCT03235245

Conditions

1. Unresectable Stage III Melanoma
2. Stage IV Melanoma

Interventions

1. Drug: Nivolumab + Ipilimumab
2. Drug: Encorafenib + Binimetinib

MeSH:Melanoma

HPO:Cutaneous melanoma Melanoma

Inclusion Criteria: - Histologically or cytologically confirmed unresectable stage III or IV cutaneous or mucosal melanoma - Presence of BRAF V600E or V600K mutation in tumor tissue prior to enrolment as per local assessment - Tumor tissue from an unresectable or metastatic site of disease must be provided for biomarker analyses. --- V600E ---

Note: Muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided while on binimetinib treatment - Impaired cardiovascular function or clinically significant cardiovascular diseases - Uncontrolled hypertension defined as persistent elevation of systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100mmHg, despite current therapy - History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤ 12 months prior to starting study treatment - History of thromboembolic or cerebrovascular events ≤ 6 months prior to starting study treatment, including stroke, transient ischemic attacks, cerebrovascular accidents, deep vein thrombosis, pulmonary emboli, aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis Inclusion Criteria: - Histologically or cytologically confirmed unresectable stage III or IV cutaneous or mucosal melanoma - Presence of BRAF V600E or V600K mutation in tumor tissue prior to enrolment as per local assessment - Tumor tissue from an unresectable or metastatic site of disease must be provided for biomarker analyses. --- V600E ---

This research study is studying an investigational combination of drugs as a possible treatment for advanced solid tumors: melanoma, ovarian, renal, or colorectal cancer. The drugs involved in this study are: - Pembrolizumab - AMG386

NCT03239145

Conditions

1. Advanced Solid Tumor

Interventions

1. Drug: Pembrolizumab
2. Drug: Trebananib

MeSH:Neoplasms

HPO:Neoplasm

Melanoma patients with BRAF V600E or V600K mutation-positive melanoma who have previously received a BRAF inhibitor with or without a MEK inhibitor) are eligible. --- V600E ---

- The association of FOLFOX (5-fluoruracil, folinic acid, and oxaliplatin) and pan is a standard option for the first-line treatment of unresectable RAS and BRAF wt mCRC patients. - The phase III TRIBE trial recently demonstrated that FOLFOXIRI (5-fluoruracil, folinic acid, oxaliplatin and irinotecan) plus bev significantly prolongs PFS and OS and increases RECIST response rate, ETS and DoR, as compared to FOLFIRI (5-fluoruracil folinic acid, and irinotecan) plus bev. The advantage provided by the intensification of the upfront chemotherapy backbone is independent of RAS and BRAF mutational status. - Some phase II trials recently assessed the safety and activity of the combination of three-drugs chemotherapy regimens with an anti-EGFR monoclonal antibody. Promising activity results in terms of RECIST response rate and R0 resection rate have been achieved, with some safety concerns with special regards to gastrointestinal toxicity. - In the phase II randomized MACBETH study the combination of a modified schedule of FOLFOXIRI with cetuximab determined remarkable activity results, with an acceptable and manageable safety profile. - The optimal duration of the upfront treatment with chemotherapy plus anti-EGFRs is not established. The phase II MACRO-2 trial suggested that interrupting FOLFOX after 4 months while continuing cet alone as maintenance, is a reasonable option. - Activity parameters (RECIST response rate, ETS, DoR) are clinically relevant endpoints, associated with longer survival, in particular with anti-EGFR moAb-based treatment. On the basis of these considerations, we designed the present phase III randomized trial of first-line mFOLFOXIRI plus pan versus mFOLFOX6 plus pan in RAS and BRAF wt unresectable mCRC patients.

NCT03231722

Conditions

1. Metastatic Colorectal Cancer

Interventions

1. Drug: Panitumumab
2. Drug: Irinotecan
3. Drug: Oxaliplatin
4. Drug: l-leucovorin
5. Drug: 5-fluorouracil

MeSH:Colorectal Neoplasms

HPO:Neoplasm of the large intestine

- RAS (codons 12, 13, 59, 61, 117 and 146 of KRAS and NRAS genes) and BRAF (V600E mutation) wt status of primary colorectal cancer or related metastasis (local or central laboratory assessment). --- V600E ---

The main purpose of this study is to see if the combination of nivolumab, ipilimumab and nintedanib is effective in people with non- small cell lung cancer. Researchers also want to find out if the combination of nivolumab, ipilimumab and nintedanib is safe and tolerable.

NCT03377023

Conditions

1. Non Small Cell Lung Cancer
2. Lung Cancer, Nonsmall Cell
3. Non Small Cell Lung Cancer Metastatic

Interventions

1. Drug: Nivolumab
2. Drug: Ipilimumab
3. Drug: Nintedanib

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

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

Patients with NSCLC tumor known to harbor a genomic aberration for which FDA approved treatment is available (i.e, non-resistant EGFR mutations, EGFR T790M mutation, ALK rearrangement, ROS rearrangement, BRAF V600E mutation) are allowed to enroll if they have received prior treatment with the FDA approved targeted therapy. --- T790M --- --- V600E ---

Patients with NSCLC tumor known to harbor a genomic aberration for which FDA approved treatment is available (i.e, non-resistant EGFR mutations, EGFR T790M mutation, ALK rearrangement, ROS rearrangement, BRAF V600E mutation) are allowed to enroll if they have received prior treatment with the FDA approved targeted therapy. --- T790M --- --- V600E ---

Patients with NSCLC tumor known to harbor a genomic aberration for which FDA approved treatment is available (i.e, non-resistant EGFR mutations, EGFR T790M mutation, ALK rearrangement, ROS rearrangement, BRAF V600E mutation) are allowed to enroll if they have received prior treatment with the FDA approved targeted therapy - At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. --- T790M --- --- V600E ---

This phase II trial is studying how well selumetinib works in treating patients with biliary cancer that cannot be removed by surgery. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

NCT00553332

Conditions

1. Liver and Intrahepatic Biliary Tract Cancer
2. Recurrent Extrahepatic Bile Duct Cancer
3. Unresectable Extrahepatic Bile Duct Cancer

Interventions

1. Drug: selumetinib
2. Other: laboratory biomarker analysis

MeSH:Bilia Biliary Tract Neoplasms Bile Duct Neoplasms Cholangiocarcinoma

HPO:Biliary tract neoplasm Cholangiocarcinoma

To genotype tumors for the presence of RAS mutations (i.e., NRAS, KRAS, HRAS) and BRAF mutations (e.g., V600E) in biliary tumor samples from these patients. --- V600E ---

This phase II trial studies how well targeted therapy works in treating patients with incurable non-small cell lung cancer with a genetic mutation. Giving drugs that target other genetic mutations or other specific proteins may work better when a patient has cancer caused by a driver mutation and the treatment that targets that mutation stops working.

NCT02949843

Conditions

1. EGFR Activating Mutation
2. Recurrent Non-Small Cell Lung Carcinoma
3. Stage IV Non-Small Cell Lung Cancer

Interventions

1. Drug: Chemotherapy
2. Biological: Immunotherapy
3. Other: Laboratory Biomarker Analysis
4. Biological: Nivolumab
5. Biological: Pembrolizumab
6. Drug: Targeted Molecular Therapy
7. Drug: Tyrosine Kinase Inhibitor

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

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

These tests will be performed overall and then separately in the three arms.. Inclusion Criteria: - Patients must have histologically or cytologically confirmed incurable non-small cell lung cancer that harbors an activating mutation in EGFR, MET, BRAF, V600E, RET, HER2, translocation in Alk, or translocation in ROS-1 - Patients must be receiving treatment or planning to start treatment with a tyrosine kinase inhibitor targeting the activated gene - Patients may not be receiving the treatment targeting the activated gene as part of a clinical treatment trial other than the Precision Oncology Trial - Eastern Cooperative Oncology Group (ECOG) performance status of 0-3 - Total bilirubin =< 1.5 X institutional upper limit of normal - Aspartate transaminase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine transaminase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal - Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately - Ability to understand and the willingness to sign an Institutional Review Board (IRB)-approved informed consent document Exclusion Criteria: - Emergent need for palliative radiation - Patients may not be receiving any other investigational agents for the treatment of non-small cell lung cancer - Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements - Pregnant women are excluded; breastfeeding should be discontinued Inclusion Criteria: - Patients must have histologically or cytologically confirmed incurable non-small cell lung cancer that harbors an activating mutation in EGFR, MET, BRAF, V600E, RET, HER2, translocation in Alk, or translocation in ROS-1 - Patients must be receiving treatment or planning to start treatment with a tyrosine kinase inhibitor targeting the activated gene - Patients may not be receiving the treatment targeting the activated gene as part of a clinical treatment trial other than the Precision Oncology Trial - Eastern Cooperative Oncology Group (ECOG) performance status of 0-3 - Total bilirubin =< 1.5 X institutional upper limit of normal - Aspartate transaminase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine transaminase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal - Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately - Ability to understand and the willingness to sign an Institutional Review Board (IRB)-approved informed consent document Exclusion Criteria: - Emergent need for palliative radiation - Patients may not be receiving any other investigational agents for the treatment of non-small cell lung cancer - Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements - Pregnant women are excluded; breastfeeding should be discontinued EGFR Activating Mutation Recurrent Non-Small Cell Lung Carcinoma Stage IV Non-Small Cell Lung Cancer Lung Neoplasms Carcinoma, Non-Small-Cell Lung PRIMARY OBJECTIVES: I. To estimate the objective response rate among patients with high PD-L1 expressing cancers after failure of targeted therapy. --- V600E ---

These tests will be performed overall and then separately in the three arms.. Inclusion Criteria: - Patients must have histologically or cytologically confirmed incurable non-small cell lung cancer that harbors an activating mutation in EGFR, MET, BRAF, V600E, RET, HER2, translocation in Alk, or translocation in ROS-1 - Patients must be receiving treatment or planning to start treatment with a tyrosine kinase inhibitor targeting the activated gene - Patients may not be receiving the treatment targeting the activated gene as part of a clinical treatment trial other than the Precision Oncology Trial - Eastern Cooperative Oncology Group (ECOG) performance status of 0-3 - Total bilirubin =< 1.5 X institutional upper limit of normal - Aspartate transaminase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine transaminase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal - Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately - Ability to understand and the willingness to sign an Institutional Review Board (IRB)-approved informed consent document Exclusion Criteria: - Emergent need for palliative radiation - Patients may not be receiving any other investigational agents for the treatment of non-small cell lung cancer - Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements - Pregnant women are excluded; breastfeeding should be discontinued Inclusion Criteria: - Patients must have histologically or cytologically confirmed incurable non-small cell lung cancer that harbors an activating mutation in EGFR, MET, BRAF, V600E, RET, HER2, translocation in Alk, or translocation in ROS-1 - Patients must be receiving treatment or planning to start treatment with a tyrosine kinase inhibitor targeting the activated gene - Patients may not be receiving the treatment targeting the activated gene as part of a clinical treatment trial other than the Precision Oncology Trial - Eastern Cooperative Oncology Group (ECOG) performance status of 0-3 - Total bilirubin =< 1.5 X institutional upper limit of normal - Aspartate transaminase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine transaminase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal - Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately - Ability to understand and the willingness to sign an Institutional Review Board (IRB)-approved informed consent document Exclusion Criteria: - Emergent need for palliative radiation - Patients may not be receiving any other investigational agents for the treatment of non-small cell lung cancer - Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements - Pregnant women are excluded; breastfeeding should be discontinued EGFR Activating Mutation Recurrent Non-Small Cell Lung Carcinoma Stage IV Non-Small Cell Lung Cancer Lung Neoplasms Carcinoma, Non-Small-Cell Lung PRIMARY OBJECTIVES: I. To estimate the objective response rate among patients with high PD-L1 expressing cancers after failure of targeted therapy. --- V600E --- --- V600E ---

This trial explores the immunologic effects of vemurafenib (BRAF inhibitor) and cobimetinib (MEK inhibitor), administered alone and in combination, to patients with advanced BRAF V600E/K mutant melanoma.

NCT02427893

Conditions

1. Melanoma

Interventions

1. Drug: Cobimetinib
2. Drug: Vemurafenib

MeSH:Melanoma

HPO:Cutaneous melanoma Melanoma

An Exploratory Study of the Immunological Effects of Vemurafenib and Cobimetinib, Administered Alone and in Combination, in Subjects With Advanced BRAF V600E/K Mutant Melanoma. --- V600E ---

Trial of Vemurafenib and Cobimetinib in Patients With Advanced BRAFV600 Mutant Melanoma This trial explores the immunologic effects of vemurafenib (BRAF inhibitor) and cobimetinib (MEK inhibitor), administered alone and in combination, to patients with advanced BRAF V600E/K mutant melanoma. --- V600E ---

This research study is evaluating a drug called clofarabine as a possible treatment for Langerhans Cell Histiocytosis (LCH) and and other histiocytic disorders.

NCT02425904

Conditions

1. Langerhans Cell Histiocytosis

Interventions

1. Drug: Clofarabine

MeSH:Histiocytosis, Langerhans-Cell Histiocytosis

HPO:Histiocytosis

ECD patients who have confirmed BRAF V600E mutation must have failed treatment with a BRAF inhibitor or are not considered to be eligible for such treatment. --- V600E ---

Immunohistochemical detection of the BRAF-V600E mutation on pre-operative fine needle aspiration biopsy (FNAB) from patients suspected for papillary thyroid carcinoma, using the mutation specific antibody VE1.

NCT02561533

Conditions

1. Papillary Thyroid Carcinoma

Interventions

1. Other: BRAF detection on fine needle aspiration biopsy (FNAB)

MeSH:Carcinoma Thyroid Neoplasms Thyroid Cancer, Papillary Thyroid Diseases

HPO:Abnormality of the thyroid gland Carcinoma Neoplasm of the thyroid gland Thyroid adenoma Thyroid carcinoma Thyroid follicular adenoma

Detection of BRAF Mutation on FNAB From Papillary Thyroid Carcinoma Immunohistochemical detection of the BRAF-V600E mutation on pre-operative fine needle aspiration biopsy (FNAB) from patients suspected for papillary thyroid carcinoma, using the mutation specific antibody VE1. --- V600E ---

Therefore, pre-operative detection of the BRAF-V600E mutation may be of clinical interest in order to individualize treatment of patients with BRAF positive PTC. --- V600E ---

FNABs are performed immediately before the thyroid operation, and BRAF-V600E detection using VE1 is performed on clots. --- V600E ---

The study plans to treat patients with pembrolizumab and thus blocking the PD-1/PD-L1 axis would render tumor-infiltrating lymphocytes (TILs) in the tumor parenchyma more functional as a consequence of BRAF inhibition, such that T cell activation by BRAFi would not be dampened by the PD-1/PD-L1 interaction. This combination would reverse dysfunction among T cells in the tumor parenchyma, maximizing T cell mediated immune anti-tumor efficacy. Progression free survival (PFS) with pembrolizumab in KEYNOTE-001 was 57% at 6 months, and 46.4% in the more recently reported phase III trial. PFS with vemurafenib treatment in BRIM-3 was ~50% at 6 months. Combined treatment with pembrolizumab, cobimetinib and vemurafenib for BRAF mutant melanoma is hypothesized to be safe and to improve the PFS compared to these recent historical controls. Because this combination has not yet been tested, and because the primary objective is to assess safety, the investigators are staging accrual in the first phase of the trial. The study aims to accrue up to 30 patients to the mTPI design of this study with the expectation that there will be at least 30 patients treated at RP2D. In case there are less than 30 patients on the RP2D, additional patients will be accrued. Patients will continue to receive treatment with pembrolizumab, vemurafenib and cobimetinib until disease progression or dose limiting toxicity. Patients with treatment response and no dose limiting toxicity may receive treatment with pembrolizumab for up to 24 months.

NCT02818023

Conditions

1. Melanoma

Interventions

1. Drug: Pembrolizumab
2. Drug: Vemurafenib
3. Drug: Cobimetinib

MeSH:Melanoma

HPO:Cutaneous melanoma Melanoma

Only patients with BRAF V600E or V600K mutated tumors will be enrolled. --- V600E ---

The primary objective of this FIH study is to assess the safety and pharmacokinetics of PLX4032 in patients with solid tumors. The secondary objective is to assess the pharmacodynamic activity in paired biopsy specimens obtained from patients with malignant melanoma who have the V600E BRAF oncogenic mutation.

NCT00405587

Conditions

1. Malignant Melanoma
2. Colorectal Carcinoma

Interventions

1. Drug: PLX4032

MeSH:Melanoma Colorectal Neoplasms

HPO:Cutaneous melanoma Melanoma Neoplasm of the large intestine

The secondary objective is to assess the pharmacodynamic activity in paired biopsy specimens obtained from patients with malignant melanoma who have the V600E BRAF oncogenic mutation. --- V600E ---

Two extension cohorts of patients with confirmed V600E mutations will be recruited, consisting of advanced melanoma and metastatic colorectal carcinoma. --- V600E ---