A Study Comparing Vemurafenib Versus Vemurafenib Plus Cobimetinib in Participants With Metastatic Melanoma
Condition: Malignant Melanoma
MeSH terms: Melanoma
Intervention: Placebo; Vemurafenib; Cobimetinib
Intervention description: Placebo supplied as tablets; Vemurafenib supplied as tablets; Cobimetinib supplied as tablets
Intervention MeSH terms: Vemurafenib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 495.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Zelboraf; vemurafenib; RG7204; PLX4032; Genentech MEK inhibitor; Genentech BRAF inhibitor; Roche MEK inhibitor; Roche BRAF inhibitor; RO5185426; metastatic melanoma; BRAF positive melanoma; BRAF mutant melanoma; advanced melanoma; Genentech RAF inhibitor; Roche RAF inhibitor; BRAF V600E kinase inhibitor; Oncogenic BRAF inhibitor; BRAF kinase inhibitor; GDC-0973; XL518; melanoma

Summary:

      To evaluate the efficacy of vemurafenib in combination with cobimetinib (GDC-0973), compared
      with vemurafenib and placebo, in previously untreated BRAF V600 mutation-positive patients
      with unresectable locally advanced or metastatic melanoma, as measured by progression-free
      survival (PFS), assessed by the study site investigator.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants 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

          -  Participants must be naïve to treatment for locally advanced unresectable or
             metastatic disease (ie, no prior systemic anti-cancer therapy for advanced disease;
             stage IIIc and IV). Prior adjuvant immunotherapy (including ipilimumab) is allowed

          -  Documentation of BRAF V600 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 greater than or equal to (≥) 12 weeks

          -  Adequate hematologic and end organ function

        Exclusion Criteria:

          -  History of prior rapidly accelerated fibrosarcoma or mitogen-activated protein kinase
             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. Participants with a previous malignancy within
             the past 3 years are excluded except for participants with resected basal cell
             carcinoma or squamous cell carcinoma 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 ophthalmological examination that is
             considered a risk factor for neurosensory retinal detachment, retinal vein occlusion,
             or neovascular macular degeneration

          -  Uncontrolled glaucoma with intraocular pressure

          -  Serum cholesterol ≥ Grade 2

          -  Hypertriglyceridemia ≥ Grade 2

          -  Hyperglycemia (fasting) ≥ Grade 2

          -  History of clinically significant cardiac dysfunction

          -  Participants with active central nervous system (CNS) lesions (including carcinomatous
             meningitis) are excluded. However, participants 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 women