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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Melanoma Research Foundation Breakthrough Consortium
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
Melanoma Research Foundation Breakthrough Consortium
ClinicalTrials.gov Identifier:
NCT01495988
First received: December 9, 2011
Last updated: April 15, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Melanoma
Metastatic Melanoma
Drug: Vemurafenib
Drug: Bevacizumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase II Trial of Vemurafenib (PLX4032/RG7204) With or Without Bevacizumab in Patients With Stage IV BRAFV600 Mutant Melanoma

Resource links provided by NLM:


Further study details as provided by Melanoma Research Foundation Breakthrough Consortium:

Primary Outcome Measures:
  • Median progression free survival [ Time Frame: Time between randomization and disease progression (~6-11 months) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: Time between randomization and death due to any cause (overall survival rates also to be assessed at 12 and 18 months) ] [ Designated as safety issue: No ]
  • Response rates and response durations [ Time Frame: From time of randomization to time of disease progression (restaging for tumor response to occur every 6 wks until wk 48, then every 12 wks thereafter) ] [ Designated as safety issue: No ]
  • Serious adverse events associated with the addition of bevacizumab [ Time Frame: While on study, patients assessed for safety/ toxicity every 3 or 6 weeks (depending on the specific toxicity) until wk 48, then every 12 wks thereafter ] [ Designated as safety issue: Yes ]
  • Effects of the addition of bevacizumab on tumor perfusion and immune function [ Time Frame: Upon completion of the protocol (3 years) ] [ Designated as safety issue: No ]
  • Correlate blood markers of B-RAFV600 mutation with treatment efficacy [ Time Frame: Upon completion of the protocol (3 years) ] [ Designated as safety issue: No ]

Estimated Enrollment: 180
Study Start Date: August 2013
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Vemurafenib alone
Vemurafenib will be given at a dose of 960 mg, orally, 2X a day 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.
Drug: Vemurafenib
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.
Other Name: Zelboraf
Experimental: Combination Vemurafenib and Bevacizumab
Patients will receive vemurafenib at a dose of 960 mg, orally, 2X a day. Bevacizumab will be administered at a dose of 15mg/kg, intravenously, 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.
Drug: Vemurafenib
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.
Other Name: Zelboraf
Drug: Bevacizumab
Patients assigned to the combination arm will also receive bevacizumab at 15mg/kg, intravenously, every 3 weeks.
Other Name: Avastin

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Metastatic or unresectable stage IIIc & clearly progressive melanoma
  • Melanoma must be documented to contain a BRAFV600E or BRAFV600K 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01495988

Contacts
Contact: Michael B Atkins, MD 617-632-9250 matkins@bidmc.harvard.edu
Contact: F. Stephen Hodi, MD 617-632-5053 stephen_hodi@dfci.harvard.edu

Locations
United States, District of Columbia
Georgetown University Medical Center Recruiting
Washington, District of Columbia, United States, 20007
Contact: Sampada Apte    202-784-2512      
Principal Investigator: Michael B Atkins, MD         
Sub-Investigator: Kellie Parks, PA         
Washington Cancer Institute at MedStar Washington Hospital Center Recruiting
Washington, District of Columbia, United States, 20010
Contact: Kate Burdekin    202-877-9374      
Principal Investigator: Sekwon Jang, MD         
Sub-Investigator: David J Perry, MD         
United States, Maryland
Harry and Jeannette Weinberg Cancer Institute at Franklin Square Recruiting
Baltimore, Maryland, United States, 21237
Contact: Jean Flack, RN    443-777-7364    jean.flack@medstar.net   
Principal Investigator: Pallavi Kumar, MD         
United States, Massachusetts
Beth Israel Deaconess Medical Center (BIDMC) Recruiting
Boston, Massachusetts, United States, 02215
Contact: Mekailah Simpson    617-632-9260      
Principal Investigator: David McDermott, MD         
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: F. Stephen Hodi, MD    617-632-5053    stephen_hodi@dfci.harvard.edu   
Principal Investigator: F S Hodi, MD         
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02114
Contact: Courtney Coughlin       ccoughlin3@partners.org   
Principal Investigator: Donald Lawrence, MD         
United States, New York
NYU Clinical Cancer Center Recruiting
New York, New York, United States, 10016
Contact: Caroline Sorlie, RN    212-731-5682    caroline.sorlie@nyumc.org   
Principal Investigator: Anna C Pavlick, DO         
NYU Langone Medical Center Recruiting
New York, New York, United States, 10016
Contact: Caroline Sorlie, RN    212-731-5682    caroline.sorlie@nyumc.org   
Principal Investigator: Anna C Pavlick, DO         
United States, Pennsylvania
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Carrie Muniz       munizca@upmc.edu   
Principal Investigator: John Kirkwood, MD         
Sub-Investigator: Hussein Tawbi, MD         
United States, Tennessee
Vanderbilt-Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: VICC Clinical Trials Information Program    800-811-8480      
Principal Investigator: Jeffrey Sosman, MD         
United States, Washington
University of Washington Medical Center Recruiting
Seattle, Washington, United States, 98195
Contact: Linda Mendelson    206-667-5767    lmendels@fhcrc.org   
Principal Investigator: Kim Margolin, MD         
Seattle Cancer Care Alliance Recruiting
Seattle, Washington, United States, 98109
Contact: Linda Mendelson    206-667-5767    lmendels@fhcrc.org   
Principal Investigator: Kim Margolin, MD         
Sponsors and Collaborators
Melanoma Research Foundation Breakthrough Consortium
Genentech
Investigators
Principal Investigator: Michael B Atkins, MD Beth Israel Deaconess Medical Center
Principal Investigator: F. Stephen Hodi, MD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Melanoma Research Foundation Breakthrough Consortium
ClinicalTrials.gov Identifier: NCT01495988     History of Changes
Other Study ID Numbers: ML27894, GEN-01
Study First Received: December 9, 2011
Last Updated: April 15, 2014
Health Authority: United States: Institutional Review Board
United States: Data and Safety Monitoring Board

Keywords provided by Melanoma Research Foundation Breakthrough Consortium:
Metastatic melanoma
BRAF-mutant
Stage IV melanoma
Vemurafenib
Bevacizumab

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 24, 2014