Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Melanoma, Cutaneous Malignant

Skin Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Entrectinib

Ceritinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Patients with MET fusion receive capmatinib PO BID on day 1-28. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.

Patients with ALK fusion receive ceritinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.

Patients with RET or BRAF fusion receive regorafenib PO QD on day 1-21. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.

Patients with NTRK1, NTRK2, NTRK3, OR ROS1 fusion receive entrectinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.

Capmatinib

Laboratory Biomarker Analysis

Regorafenib

Adil Daud

This phase II trial studies how well capmatinib, ceritinib, regorafenib, or entrectinib work in treating patients with BRAF/NRAS wild-type stage III-IV melanoma. Capmatinib, ceritinib, regorafenib, or entrectinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To estimate the clinical activity of tyrosine kinase inhibitors matched to the tumor-specific fusion kinase in patients with metastatic melanoma.

SECONDARY OBJECTIVES:

I. To estimate tumor stability in melanoma patients treated with kinase inhibitors matched to the tumor-specific fusion kinase.

II. To estimate survival in melanoma patients treated with kinase inhibitors matched to the tumor-specific fusion kinase.

III. To examine the safety and tolerability of kinase inhibitors in patients with melanoma with a fusion kinase.

TERTIARY OBJECTIVES:

I. To explore molecular mechanisms of resistance for patients who progress on therapy.

OUTLINE: Patients are assigned to 1 of 4 arms.

ARM A: Patients with MET fusion receive capmatinib orally (PO) twice daily (BID) on day 1-28. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.

ARM B: Patients with ALK fusion receive ceritinib PO once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.

ARM C: Patients with RET or BRAF fusion receive regorafenib PO QD on day 1-21. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.

ARM D: Patients with NTRK1, NTRK2, NTRK3, or ROS1 fusion receive entrectinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.

After completion of study treatment, patients are followed up within 30 days and then periodically.

Capmatinib, Ceritinib, Regorafenib, or Entrectinib in Treating Patients With BRAF/NRAS Wild-Type Stage III-IV Melanoma

A Phase II Trial of Targeted Kinase Fusion Inhibition in Unresectable Stage III/IV BRAF/NRAS Wild-Type Melanoma

Defined as a complete or partial response as per Response Evaluation Criteria in Solid Tumors version 1.1 criteria with confirmatory measurements a minimum of 4 weeks after the response-defining determination. Analysis of study results will include ORR estimations of ALK, NTRK, ROS1, RET, MET, and BRAF rearrangement-positive patients.

Clinical benefit rate is defined as the proportion of patients achieving a complete response (CR) or partial response (PR) or stable disease (SD) for \> 24 weeks using the same RECIST 1.1 decision matrix used to calculate ORR. The CBR will be estimated for each arm along with a 95% confidence interval

Overall defined as the time from treatment start to the progression or death and overall survival defined as the time from treatment start to death will be estimated using Kaplan-Meier methodology.

Progression free survival (PFS) defined as the time from treatment start to the progression or death and overall survival defined as the time from treatment start to death will be estimated using Kaplan-Meier methodology

Frequencies of toxicities will be tabulated according to CTCAE v4.03 to assess drug safety and tolerability

University of California, San Francisco

Principal Investigator

Analyses will be performed for all participants having received at least one dose of study drug. Only one participant was enrolled on this trial to Arm C (Regorafenib) for a total of 3 months. Adverse Events reported are for single accrued participant

Arm C (Regorafenib)

60-65 years

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Only 1 participant was enrolled on this protocol to Arm C (regorafenib). Evaluable patients would be those with baseline staging, treatment for at least 8 weeks, and at least one post-baseline staging scan while on treatment. No participants meet the criteria to be considered evaluable for this protocol.

Only 1 participant was enrolled on this study to Arm C (regorafenib) based on the participants mutation profile. The study was terminated after one accrual due to lack of funding.

Dr. Adil Daud

Evaluable participants would be those with baseline staging, treatment for at least 8 weeks, and at least one post-baseline staging scan while on treatment. No participants meet the criteria to be considered evaluable for this analysis.

Confirmed Overall Response Rate (ORR)

Evaluable patients would be those with baseline staging, treatment for at least 8 weeks, and at least one post-baseline staging scan while on treatment. No participants meet the criteria to be considered evaluable for this analysis.

Clinical Benefit Rate (CBR)

Overall Survival

Progression Free Survival

Evaluation of the Adverse Effect Profile of Each Kinase Inhibitor

Patients with MET fusion receive capmatinib orally (PO), twice a day (BID) on day 1-28. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.

Capmatinib: Given orally

Laboratory Biomarker Analysis: Correlative studies

Arm A (Capmatinib)

Patients with ALK fusion receive ceritinib PO once a day (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.

Ceritinib: Given PO

Laboratory Biomarker Analysis: Correlative studies

Arm B (Ceritinib)

Patients with RET or BRAF fusion receive regorafenib PO QD on day 1-21. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.

Laboratory Biomarker Analysis: Correlative studies

Regorafenib: Given PO

Patients with NTRK1, NTRK2, NTRK3, OR ROS1 fusion receive entrectinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.

Entrectinib: Given PO

Laboratory Biomarker Analysis: Correlative studies

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Capmatinib, Ceritinib, Regorafenib, or Entrectinib in Treating Patients With BRAF/NRAS Wild-Type Stage III-IV Melanoma	NCT02587650	ALK Fusion Prot... BRAF wt Allele Invasive Skin M... MET Fusion Gene... NRAS wt Allele NTRK1 Fusion Po... NTRK2 Fusion Po... NTRK3 Fusion Po... RET Fusion Posi... ROS1 Fusion Pos... Stage III Cutan... Stage IIIA Cuta... Stage IIIB Cuta... Stage IIIC Cuta... Stage IV Cutane...	Capmatinib Ceritinib Entrectinib Laboratory Biom... Regorafenib	18 Years -	University of California, San Francisco
Capmatinib, Ceritinib, Regorafenib, or Entrectinib in Treating Patients With BRAF/NRAS Wild-Type Stage III-IV Melanoma	NCT02587650	ALK Fusion Prot... BRAF wt Allele Invasive Skin M... MET Fusion Gene... NRAS wt Allele NTRK1 Fusion Po... NTRK2 Fusion Po... NTRK3 Fusion Po... RET Fusion Posi... ROS1 Fusion Pos... Stage III Cutan... Stage IIIA Cuta... Stage IIIB Cuta... Stage IIIC Cuta... Stage IV Cutane...	Capmatinib Ceritinib Entrectinib Laboratory Biom... Regorafenib	18 Years -	University of California, San Francisco
Capmatinib, Ceritinib, Regorafenib, or Entrectinib in Treating Patients With BRAF/NRAS Wild-Type Stage III-IV Melanoma	NCT02587650	ALK Fusion Prot... BRAF wt Allele Invasive Skin M... MET Fusion Gene... NRAS wt Allele NTRK1 Fusion Po... NTRK2 Fusion Po... NTRK3 Fusion Po... RET Fusion Posi... ROS1 Fusion Pos... Stage III Cutan... Stage IIIA Cuta... Stage IIIB Cuta... Stage IIIC Cuta... Stage IV Cutane...	Capmatinib Ceritinib Entrectinib Laboratory Biom... Regorafenib	18 Years -	University of California, San Francisco

Spots Global Cancer Trial Database for met fusion gene positive