coBRIM: A Phase 3 Study Comparing GDC-0973 (Cobimetinib), a MEK Inhibitor, in Combination With Vemurafenib vs Vemurafenib Alone in Patients With Metastatic Melanoma
Basic Trial Information
|Phase III||Biomarker/Laboratory analysis, Treatment||Closed||18 and over||Pharmaceutical / Industry||GO28141|
This multicenter, randomized, double-blind, placebo-controlled phase 3 study will evaluate the safety and efficacy of vemurafenib alone and vemurafenib in combination with GDC-0973 (cobimetinib), a MEK inhibitor, in previously untreated BRAF V600 mutation-positive patients with unresectable locally advanced or metastatic melanoma. Patients will be randomized to one of two treatment arms, Arm A: vemurafenib 960 mg twice a day (days 1-28 of each cycle) and placebo (days 1-21 of each cycle); Arm B: vemurafenib 960 mg twice a day (days 1-28 of each cycle) and GDC-0973 (cobimetinib) 60 mg once daily (days 1-21 of each cycle). Patients will receive treatment until disease progression, unacceptable toxicity or withdrawal of consent.
- Patients with histologically confirmed melanoma, either unresectable stage IIIc or stage IV metastatic melanoma, as defined by the American Joint Committee on Cancer 7th edition.
- Unresectability of stage IIIc disease must have confirmation from a surgical oncologist.
- Patients must be naïve to treatment for locally advanced unresectable or metastatic disease (i.e., no prior systemic anti-cancer therapy for advanced disease; stage IIIc and IV). Prior adjuvant immunotherapy (including ipilimumab) is allowed.
- Documentation of BRAFV600 mutation-positive status in melanoma tumor tissue (archival or newly obtained tumor samples) using the cobas 4800 BRAF V600 mutation test.
- Measurable disease per RECIST v1.1.
- Eastern Clinical Oncology Group performance status of 0 or 1.
- Consent to provide archival for biomarker analyses.
- Consent to undergo tumor biopsies for biomarker analyses.
- Life expectancy >/= 12 weeks.
- Adequate hematologic and end organ function
- History of prior RAF or MEK pathway inhibitor treatment.
- Palliative radiotherapy within 14 days prior to the first dose of study treatment.
- Major surgery or traumatic injury within 14 days prior to first dose of study treatment.
- Active malignancy other than melanoma that could potentially interfere with the interpretation of efficacy measures. Patients with a previous malignancy within the past 3 years are excluded except for patients with resected basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) of the skin, melanoma in-situ, carcinoma in-situ of the cervix, and carcinoma in-situ of the breast.
- History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, retinal vein occlusion (RVO), or neovascular macular degeneration.
- Uncontrolled glaucoma with intra-ocular pressures
- Serum cholesterol >/= Grade 2
- Hypertriglyceridemia >/= Grade 2
- Hyperglycemia (fasting) >/= Grade 2
- History of clinically significant cardiac dysfunction
- Patients with active CNS lesions (including carcinomatous meningitis) are excluded. However, patients are eligible if:
1. All known CNS lesions have been treated with stereotactic therapy or surgery, AND
2. There has been no evidence of clinical and radiographic disease progression in the CNS for >/= 3 weeks after radiotherapy or surgery
- Current severe, uncontrolled systemic disease.
- History of malabsorption or other condition that would interfere with absorption of study drugs.
- Pregnant, lactating, or breast feeding.
Trial Contact Information
Trial Lead Organizations/Sponsors
F. Hoffmann - La Roche, Limited
Link to the current ClinicalTrials.gov record.
NLM Identifier NCT01689519
ClinicalTrials.gov processed this data on May 19, 2015
Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.