Overview

This trial is active, not recruiting.

Condition malignant melanoma
Treatments gdc-0973, vemurafenib
Phase phase 1
Targets BRAF, MEK
Sponsor Hoffmann-La Roche
Start date February 2011
End date December 2016
Trial size 131 participants
Trial identifier NCT01271803, NO25395

Summary

This open-label, dose-escalation study of vemurafenib in combination with GDC-0973 will evaluate the safety, tolerability and pharmacokinetics in patients with BRAF V600 mutation-positive metastatic melanoma. Patients with previously untreated, BRAFV600E mutation-positive, locally advanced/unresectable or metastatic melanoma or those who have progressed on vemurafenib monotherapy immediately prior to enrolling in this trial are eligible. Patients will be assigned to different cohorts with escalating oral doses of vemurafenib and GDC-0973. The anticipated time on study treatment is until disease progression, unacceptable toxicity or any other discontinuation criterion.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
gdc-0973
Oral repeated dose
vemurafenib
Oral repeated dose

Primary Outcomes

Measure
Dose-limiting toxicity of vemurafenib in combination with GDC-0973
time frame: Cycle 1: Day 28
Maximum tolerated dose of vemurafenib in combination with GDC-0973
time frame: Cycle 1: Day 28
Safety (Incidence of adverse events)
time frame: Approximately 2 years
Steady state plasma concentrations
time frame: Cycle 1: Predose, Days 1, 2, 8, 14, 15, 16, 17; Cycle 2: Day 1, 8; Cycle 3: Day 8; at disease progression

Secondary Outcomes

Measure
Objective response
time frame: Approximately 2 years
Progression-free survival
time frame: Approximately 2 years
Duration of response
time frame: Approximately 2 years
Overall survival
time frame: Approximately 2 years
Pharmacodynamics: Change in fluorodeoxyglucose-positron emission tomography (FDG-PET)
time frame: At baseline; Cycle 1, Day 14: Cycle 2, Day 14; at disease progression
Pharmacodynamics: Immunohistochemical assessment of biopsies (MAP kinase)
time frame: At baseline; Cycle 1: Day 14; at disease progression

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Adult patients, age >/=18 years - Patients with histologically confirmed metastatic melanoma (unresectable Stage IIIc and Stage IV, American Joint Committee on Cancer (AJCC) metastatic melanoma) - Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 - Eastern Cooperative Oncology Group (ECOG) Performance Status of /=12 weeks Exclusion Criteria: - History of prior significant toxicity from another RAF or MEK pathway inhibitor requiring discontinuation of treatment - Palliative radiotherapy within 2 weeks prior to first dose of study drug treatment - Experimental therapy within 4 weeks prior to first dose of study drug treatment except vemurafenib - Major surgery within 4 weeks of first dose of study drug treatment or planning a major surgery during the study

Additional Information

Official title A Phase IB, Open-Label, Dose-Escalation Study Evaluating the Safety, Tolerability and Pharmacokinetics of Vemurafenib in Combination With GDC-0973 When Administered in BRAFV600E Mutation-Positive Patients Previously Treated (But Without Prior Exposure to BRAF or MEK Inhibitor Therapy) or Previously Untreated for Locally- Advanced/Unresectable or Metastatic Melanoma or Those Who Have Progressed After Treatment With Vemurafenib
Trial information was received from ClinicalTrials.gov and was last updated in December 2015.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.