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

NCT02587650 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 14859NCI-2017-01421
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief 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.

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

Outcome Measures

Primary Outcomes (1)

• Confirmed Overall Response Rate (ORR)

  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.

  24 weeks

Secondary Outcomes (4)

• Clinical Benefit Rate (CBR)

  Up to 2 years

• Overall Survival

  From treatment start to death, assessed up to 2 years

• Progression Free Survival

  up to 2 years

• Evaluation of the Adverse Effect Profile of Each Kinase Inhibitor

  Up to 2 years

Study Arms (4)

Arm A (capmatinib)

EXPERIMENTAL

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.

Drug: Capmatinib; Other: Laboratory Biomarker Analysis

Arm B (ceritinib)

EXPERIMENTAL

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.

Drug: Ceritinib; Other: Laboratory Biomarker Analysis

Arm C (regorafenib)

EXPERIMENTAL

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.

Other: Laboratory Biomarker Analysis; Drug: Regorafenib

Arm D (entrectinib)

EXPERIMENTAL

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.

Drug: Entrectinib; Other: Laboratory Biomarker Analysis

Interventions

Capmatinib DRUG

Given PO

Also known as: INC-280, INC280, INCB 28060, INCB028060, INCB28060

Arm A (capmatinib)

Ceritinib DRUG

Given PO

Also known as: LDK 378, LDK378, Zykadia

Arm B (ceritinib)

Entrectinib DRUG

Given PO

Also known as: RXDX-101

Arm D (entrectinib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm A (capmatinib); Arm B (ceritinib); Arm C (regorafenib); Arm D (entrectinib)

Regorafenib DRUG

Given PO

Also known as: BAY 73-4506, Stivarga

Arm C (regorafenib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to understand a written informed consent document, and the willingness to sign it
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Life expectancy \>= 12 weeks
• Histologically or cytologically confirmed invasive melanoma
• Unresectable stage III or stage IV melanoma by clinical or radiographic criteria
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
• Documentation of absence of activating and targetable BRAF or NRAS point mutations
• Presence of an oncogenic kinase fusion involving MET, confirmed by assay by a Clinical Laboratory Improvement Act (CLIA)-approved laboratory
• Prior treatment with at least one Food and Drug Administration (FDA)-approved drug for unresectable/metastatic melanoma; patients who are treatment-naive but who refuse available standard options and prefer to enroll on this study as their first line of treatment after a thorough informed consent process will be eligible at the discretion of the treating physician
• Resolution of all acute toxic effects (excluding alopecia) of prior radiotherapy, chemotherapy or surgical procedures to Common Terminology Criteria for Adverse Events (CTCAE) v4.03 grade =\< 1
• Absolute neutrophil count \>= 1,500/mm\^3
• Platelets \>= 75,000/ microliters (mcL)
• Hemoglobin \>= 9 g/dL (transfusions are allowed)
• Total bilirubin =\< 1.5 x upper limit of normal (ULN); patients with Gilbert?s syndrome may be included if total bilirubin =\< 3 x ULN or direct bilirubin =\< 1.5 x ULN
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x ULN if no liver metastases are present? =\< 5 x ULN if liver metastases are present

You may not qualify if:

• Any prior treatment with capmatinib, crizotinib, or any other cMET or hepatocyte growth factor (HGF) inhibitor
• Thoracic radiotherapy to lung fields =\< 4 weeks prior to starting capmatinib; for all other anatomic sites (including radiotherapy to thoracic vertebrae and ribs), radiotherapy =\< 2 weeks prior to starting capmatinib; palliative radiotherapy for bone lesions =\< 2 weeks prior to starting capmatinib is allowed
• Receipt of any anticancer or investigational agent within 4 weeks or =\< 5 half-lives of the agent (whichever is longer) prior to the first dose of capmatinib; if previous treatment is a monoclonal antibody, then the treatment must be discontinued at least 4 weeks before the first dose of capmatinib
• Strong and moderate inhibitors of CYP3A4
• Strong inducers of CYP3A4
• Proton pump inhibitors (PPI)
• Patients with asymptomatic brain metastases may be enrolled at the discretion of the sponsor as long as the patient is stable and has not required increasing dose of steroids to manage CNS symptoms for at least 2 weeks prior to study enrollment
• Patients requiring seizure prophylaxis must be taking non-enzyme-inducing anti-epileptic drugs (non-EIAED); if patients were previously on EIAEDs and these have been discontinued, they must be discontinued for at least 1 weeks prior to capmatinib administration; if patients re

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94115, United States

Location

MeSH Terms

Conditions

Noonan Syndrome 6; Melanoma

Interventions

capmatinib; ceritinib; entrectinib; regorafenib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

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.

Results Point of Contact

• Title: Dr. Adil Daud
• Organization: University of California, San Francisco

Adil.Daud@ucsf.edu

(415) 353-7392

Study Officials

• Adil Daud

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 23, 2015
• First Posted: October 27, 2015
• Study Start: March 26, 2015
• Primary Completion: July 12, 2018
• Study Completion: July 12, 2018
• Last Updated: January 27, 2020
• Results First Posted: January 27, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)