The Effects of Treatment With Vemurafenib on the Immune System in Advanced Melanoma
Status:
Terminated
Trial end date:
2015-11-01
Target enrollment:
Participant gender:
Summary
Approximately 40-60 % of cutaneous melanomas select for a mutation in a protein called BRAF
which is part of a signaling pathway called the Mitogen Activated Protein Kinase (MAPK)
pathway. When BRAF is mutated the MAPK pathway remains active allowing for melanoma to grow.
Vemurafenib is an oral treatment which blocks the activity of BRAF which leads to decreasing
the activity of the MAPK pathway. When patients with melanoma expressing specific mutation in
BRAF are treated with vemurafenib approximately 50% will develop a response to treatment with
shrinkage of tumor. When compared to a standard chemotherapy called dacarbazine used to treat
melanoma, treatment with vemurafenib leads to a statistically significant overall survival or
living longer benefit. Because of this survival benefit vemurafenib was Food and Drug
Administration (FDA) approved for the treatment of metastatic melanoma expressing a BRAF
mutation called V600E BRAF. There is increasing evidence that the immune system can also be
important in affecting melanoma growth and survival and there are immune treatments FDA
approved for the treatment of metastatic melanoma. There is some limited evidence that
blocking BRAF with vemurafenib may affect the activity of components of the immune system. It
is important to better characterize and understand the effects of vemurafenib treatment on
various components of the immune system. The purpose of this study is to systematically
evaluate the effects of vemurafenib treatment (at FDA approved dosing regimen) on parts of
the immune systems called the innate and adaptive immune systems. The hypothesis is that
vemurafenib treatment will affect the immune system.