The Effect of BRAF Inhibition with Vemurafenib on the Innate and Adaptive Immune Systems in Patients with Unresectable Stage III or Stage IV Melanoma Expressing a V600 BRAF Mutation
ID Number 13-0427Principal Investigator(s)
Department(s) or Division(s)
Hematology and Medical Oncology
The purpose of this study is to learn if and how treatment with vemurafenib affects the immune system. The 'immune system' defends against infection-causing foreign organisms (like viruses or bacteria), and other diseases (like cancer) and tries to protect the body by making antibodies (special proteins) to destory the organisms or cancer. There is some suggestion that vemurafenib may have anti-tumor abilities by having an effect on parts of the immune system, but this has not been thoroughly studied. The research will include receiving vemurafenib and collecting blood and tumor tissue by biopsy at several time points so that the blood and tumor tissue can be studied in a laboratory to determine if there are changes in the immune system when taking vemurafenib. A biopsy is a procedure performed to remove a small piece of tissue from your tumor for laboratory evaluation and will only be performed if tumor is present of the skin surface or just below the skin.
Vemurafenib is Food and Drug Administration (FDA)-approved for treatment of people with stage IV melanoma with specific V600E mutation in a cell protein called BRAF. BRAF regulates cell growth. A mutation is a permanent change in a cell's DNA. Vemurafenib is an oral medication that blocks the activity of BRAF. It was FDA-approved because treatment leads to a statistically significant (meaning researchers are very sure that the findings are reliable and didn't happen by chance) overall survival or living longer benefit. The FDA-approved dosing is 960 milligrams orally twice a day and that is the dosing to be used in the study.
As part of this study you will receive vemurafenib at the FDA-approved dosing and in addition to your standard of care, you will have extra blood drawn for research purposes at specified time points. This extra blood will be used to study the effects of vemurafenib treatment on the function of the immune system in the blood. In addition, if your tumor spreads on the skin or just below the skin, you may have biopsies of the tumor at specific time points to be used to learn the effect of vemurafenib on the immune system in the tumor directly.
You may qualify to take part in this research study because you have stage III or stage IV melanoma with a V600 BRAF mutation that cannot be removed by surgery. At least 5 of the 15 subjects in the study must have at least two areas where the tumor has spread on or just below the skin that can be biopsied and at least 5 of the 15 patients in the study must agree to these biopsies of tumor.
Funds for conducting this research are provided by Genentech, the manufacturer of vemurafenib, and by the Tisch Cancer Institute at Mount Sinai Medical Center.
Recruiting Patients: Yes