Trial of Vemurafenib/Cobimetinib With or Without Bevacizumab in Patients With Stage IV BRAFV600 Mutant Melanoma

Conditions

• Melanoma
• Metastatic Melanoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Vemurafenib — DRUG
  Vemurafenib will be given at a dose of 960 mg, orally, 2X a day to all patients until disease progression, intolerable toxicity, patient request for discontinuation, or study termination by the sponsor.
• Bevacizumab — DRUG
  Patients assigned to the combination arm will also receive bevacizumab at 15mg/kg, intravenously, every 3 weeks.
• Cobimetinib — DRUG
  Cobimetinib will be given at a dose of 60mg, orally, 1X a day to all patients for 21 days, then 7 days off, in a 28 day treatment cycle.

Study Details

This phase 2 clinical trial randomizes patients with BRAF mutant melanoma to either (1) standard of care (SOC) - BRAF inhibitor vemurafenib in combination with MEK inhibitor cobimetinib; or, (2) SOC plus bevacizumab, an anti-VEGF antibody that suppresses new blood vessel formation and can stimulate the immune system. Previous clinical studies in melanoma have shown that bevacizumab may improve clinical benefit (progression free survival) if combined with ipilimumab or abraxane. Preclinical studies suggest that VEGF increase plays a role in resistance to BRAF inhibitors. This randomized study will ask whether the addition of bevacizumab to targeted therapy SOC in BRAF mutant melanoma can improve response rates and clinical benefit. Patients may have received no therapy for advanced disease or up to 2 prior therapies, excluding BRAF and MEK inhibitors.

Key Dates

First listed

Dec 21, 2011

Start date

Aug 31, 2013

Status verified

Sep 2017

Primary completion

Jan 31, 2016

Completion

Jun 30, 2016

Study Design

Enrollment

10 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Active Comparator: Vemurafenib/Cobimetinib
  Vemurafenib will be given at a dose of 960 mg, orally, 2X a day to all patients. Cobimetinib will be given at a dose of 60mg, orally, 1X a day to all patients for 21 days, then 7 days off, in a 28 day treatment cycle. Patients will be assessed for toxicity every 4 weeks and be restaged for tumor response/progression every 8 weeks until week 48, then every 12 weeks thereafter. Patients will be followed until disease progression.
• Experimental: Vemurafenib/Cobimetinib + Bevacizumab
  Vemurafenib will be given at a dose of 960 mg, orally, 2X a day to all patients. Cobimetinib will be given at a dose of 60mg, orally, 1X a day to all patients for 21 days, then 7 days off, in a 28 day treatment cycle. Bevacizumab will be administered at the MTD (determined by phase Ib safety lead-in), intravenously, every 2 weeks. Patients will be assessed for toxicity every 4 weeks and be restaged for tumor response/progression every 8 weeks until week 48, then every 12 weeks thereafter. Patients will be followed until disease progression.
• Active Comparator: Vemurafenib
  Vemurafenib will be given at a dose of 960 mg p.o. BID to all patients. Patients will be assessed for toxicity every 3 or 6 weeks (depending on the specific toxicity) and be restaged for tumor response/progression every 6 weeks until week 48, then every 12 weeks thereafter. Patients will be followed until disease progression.
• Experimental: Vemurafenib + Bevacizumab
  Vemurafenib will be given at a dose of 960 mg p.o. BID to all patients. Patients assigned to the combination arm will also receive bevacizumab 15 mg/kg every IV every 3 weeks. Patients will be assessed for toxicity every 3 or 6 weeks (depending on the specific toxicity) and be restaged for tumor response/progression every 6 weeks until week 48, then every 12 weeks thereafter. Patients will be followed until disease progression.

Primary Outcome Measure

Maximum Tolerated Dose [ Time Frame: Until MTD determined (up to 6 months) ]

Locations (14)

Find similar trials in Los Angeles, CA

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