Clinical Trials Logo

Clinical Trial Summary

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.


Clinical Trial Description

In this study, the drugs being used are vemurafenib, cobimetinib, and bevacizumab. Vemurafenib has been approved by the FDA for treatment of patients with advanced melanoma that harbors a BRAF mutation. However, vemurafenib in combination with cobimetinib has not been approved by the FDA for the treatment of cancer. 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. Bevacizumab has not been approved for use in patients with metastatic melanoma.

Vemurafenib and cobimetinib attack different proteins that cause cancer cells to grow. 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. Cobimetinib works by blocking a protein called MEK. MEK has been known to promote growth in cancer that carries either a mutation in the BRAF or KRAS genes. The vemurafenib/cobimetinib combination has been used in prior clinical studies. Information from those other research studies suggests that these drugs can shrink melanoma tumors in the majority of patients and slow tumor growth as compared to standard chemotherapy. Another drug to block the BRAF and MEK proteins was recently approved by the FDA in the treatment of patients with B-RAFV600 mutant melanoma. The researchers want to see if using vemurafenib and cobimetinib together will work in a similar way to treat malignant 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) produced by using recombinant DNA technology. Bevacizumab is an antibody directed against vascular endothelial growth factor or VEGF. VEGF is a potent, specific growth factor with a well-defined role in normal and abnormal blood vessel formation. It is present in a wide variety of normal tissues, but is produced in excess by most solid cancers (tumors). In the setting of cancer, 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 tumors types including melanoma. In laboratory experiments, bevacizumab inhibits the growth of several different types of human cancer cells by blocking the effects of VEGF.

The purpose of this research study is to determine the effectiveness of using the study drugs vemurafenib, cobimetinib, and bevacizumab together relative to vemurafenib and cobimetinib alone. This study will investigate whether using both study drugs lengthens the amount of time before participants' melanoma worsens, increases the number of people whose melanoma responds to treatment and what the side effects are of using the drugs together rather than separately. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT01495988
Study type Interventional
Source Melanoma Research Foundation Breakthrough Consortium
Contact
Status Terminated
Phase Phase 2
Start date August 2013
Completion date June 2016

See also
  Status Clinical Trial Phase
Recruiting NCT05094804 - A Study of OR2805, a Monoclonal Antibody Targeting CD163, Alone and in Combination With Anticancer Agents Phase 1/Phase 2
Completed NCT03979872 - Risk Information and Skin-cancer Education for Undergraduate Prevention N/A
Recruiting NCT04986748 - Using QPOP to Predict Treatment for Sarcomas and Melanomas
Enrolling by invitation NCT00068003 - Harvesting Cells for Experimental Cancer Treatments
Recruiting NCT05707286 - Pilot Study to Determine Pro-Inflammatory Cytokine Kinetics During Immune Checkpoint Inhibitor Therapy
Active, not recruiting NCT05470283 - Phase I, Open-Label, Study of Tumor Infiltrating Lymphocytes Engineered With Membrane Bound IL15 Plus Acetazolamide in Adult Patients With Metastatic Melanoma Phase 1
Recruiting NCT05077137 - A Feasibility Study Utilizing Immune Recall to Increase Response to Checkpoint Therapy Phase 1
Active, not recruiting NCT02721459 - XL888 + Vemurafenib + Cobimetinib for Unresectable BRAF Mutated Stage III/IV Melanoma Phase 1
Completed NCT00341939 - Retrospective Analysis of a Drug-Metabolizing Genotype in Cancer Patients and Correlation With Pharmacokinetic and Pharmacodynamics Data
Recruiting NCT05839912 - Excision of Lymph Node Trial (EXCILYNT) (Mel69) N/A
Recruiting NCT04971499 - A Study of Dapansutrile Plus Pembrolizumab in Patients With PD-1 Refractory Advanced Melanoma Phase 1/Phase 2
Recruiting NCT05263453 - HL-085+Vemurafenib to Treat Advanced Melanoma Patients With BRAF V600E/K Mutation Phase 2
Active, not recruiting NCT05060432 - Study of EOS-448 With Standard of Care and/or Investigational Therapies in Participants With Advanced Solid Tumors Phase 1/Phase 2
Not yet recruiting NCT06413680 - A First-In Human (FIH) Trial to Find Out if REGN10597 is Safe and How Well it Works for Adult Participants With Advanced Solid Organ Malignancies Phase 1/Phase 2
Terminated NCT03399448 - NY-ESO-1-redirected CRISPR (TCRendo and PD1) Edited T Cells (NYCE T Cells) Phase 1
Completed NCT03348891 - TNF in Melanoma Patients Treated With Immunotherapy N/A
Completed NCT03171064 - Exercise as a Supportive Measure for Patients Undergoing Checkpoint-inhibitor Treatment Phase 2
Not yet recruiting NCT05539118 - Interferon-α1b Combined With Toripalimab and Anlotinib Hydrochloride in Advanced Unresectable Melanoma Phase 1/Phase 2
Recruiting NCT05171374 - pRospective Evaluation of Clinical Outcomes in Patients With metAsTatIс melanOma Treated With dabrafeNib and trAmetinib in reaL practicE
Withdrawn NCT02854488 - Yervoy Pregnancy Surveillance Study