NCT02587650

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

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 1 (actual)
• Sponsor: University of California, San Francisco · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• ALK Fusion Protein Expression
• BRAF wt Allele
• Invasive Skin Melanoma
• MET Fusion Gene Positive
• NRAS wt Allele
• NTRK1 Fusion Positive
• NTRK2 Fusion Positive
• NTRK3 Fusion Positive
• RET Fusion Positive
• ROS1 Fusion Positive
• Stage III Cutaneous Melanoma
• Stage IIIA Cutaneous Melanoma
• Stage IIIB Cutaneous Melanoma
• Stage IIIC Cutaneous Melanoma
• Stage IV Cutaneous Melanoma

Interventions

Type	Name	Description
DRUG	Capmatinib	Given PO
DRUG	Ceritinib	Given PO
DRUG	Entrectinib	Given PO
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Regorafenib	Given PO

Timeline

• Start date: 2015-03-26
• Primary completion: 2018-07-12
• Completion: 2018-07-12
• First posted: 2015-10-27
• Last updated: 2020-01-27
• Results posted: 2020-01-27

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study