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

Status: Recruiting
Phase: Phase 2
Diagnosis: Cutaneous Skin Cancer
NCT ID: NCT01495988 (View complete trial on
DFCI Protocol ID: 12-342


In this study, the drugs being used are vemurafenib and bevacizumab. Vemurafenib works by blocking a protein called B-RAF. Researchers have found that a large number of melanomas have mutations (changes) in the BRAF gene. The BRAF gene codes for a protein called B-RAF, which is involved in sending signals in cells that can lead to cell growth. Research has determined that mutations in the BRAF gene at the V600 position cause a change in the B-RAF protein that can drive the growth and spread of melanoma cells. Vemurafenib works by preventing these altered B-RAF proteins from working, and thereby may block the growth and spread of cancer cells in patients with melanoma. Information from prior research studies suggests that this drug can shrink melanoma tumors in the majority of patients, delay tumor growth and prolong overall survival relative to standard chemotherapy. As a consequence, vemurafenib received FDA approval in August 2011 for the treatment of patients with B-RAFV600 mutant melanoma. Bevacizumab is a humanized monoclonal antibody (a type of protein that is normally made by the immune system to help defend the body from infection and cancer) directed against vascular endothelial growth factor (VEGF). VEGF is a potent growth factor with a well-defined role in normal and abnormal blood vessel formation. In the cancer setting, VEGF promotes the growth of blood vessels that bring nutrients to tumor cells. Its expression by the tumor has been associated with worse outcome in patients with a number of tumor types including melanoma. In laboratory experiments, bevacizumab inhibits the growth of several different types of human cancer cells by blocking the effects of VEGF. Bevacizumab has been approved by the FDA for use in combination with first line chemotherapies for treatment of patients with colorectal, breast and lung cancer; however, bevacizumab has not been approved for use in patients with metastatic melanoma. The purpose of this research study is to determine the effectiveness of using vemurafenib and bevacizumab together relative to vemurafenib alone. This study will investigate whether using both study drugs lengthens the amount of time before a patient's melanoma worsens, increases the number of people whose melanoma responds to treatment and what side effects are associated with the use of both drugs together rather than separately.


Conducting Institutions:
Dana-Farber Cancer Institute, Brigham and Women's Hospital, Beth-Israel Deaconess Medical Center, Massachusetts General Hospital

Overall PI:
Frank Stephen Hodi, MD, Dana-Farber Cancer Institute

Site-responsible Investigators:
David McDermott, MD, Beth Israel Deaconess Medical Center

Dana-Farber Cancer Institute: Suzanne MacRae, 617-632-5906,
Beth-Israel Deaconess Medical Center: Cancer Trials Call Center, 617-667-3060

Eligibility Criteria

Inclusion Criteria: - Metastatic or unresectable stage IIIc & clearly progressive melanoma - Melanoma must be documented to contain a BRAFV600 mutation - Measurable disease - No more than 2 prior systemic treatment regimens for distant metastatic disease. The following prior therapy is permitted in either the adjuvant or metastatic setting: immunotherapy consisting of interferon, interleukin-2, GM-CSF, ipilimumab, anti-PD1 or other experimental agent; and cytotoxic chemotherapy consisting of dacarbazine, temozolomide, carboplatin +/- paclitaxel - ECOG performance status of 0, 1, or 2 Exclusion Criteria: - Pregnant or nursing mothers - Treatment with a prior VEGF pathway, BRAF, or MEK inhibitor(s) - Receipt of any other investigational agents during the period on study or the four weeks prior to entry - Clinical evidence of active brain metastasis - Concurrent uncontrolled malignancies that require therapy or other intervention - Major surgical procedure, open biopsy (excluding skin cancer resection), or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study - Core biopsy, skin cancer resection, or other minor surgical procedure within 7 days prior to Day 1 of the protocol - Serious intercurrent illness - HIV-positive patients receiving combination anti-retroviral therapy
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