Combined BRAF-Targeted Therapy & Immunotherapy for Melanoma

Status: Recruiting
Phase: Phase 2
Diagnosis: Cutaneous Skin Cancer
NCT ID: NCT01754376 (View complete trial on
DFCI Protocol ID: 12-343


This research study is a Phase II clinical trial of an investigational combination of drugs (vemurafenib and aldesleukin) to learn whether the combination works in treating a specific cancer. While both vemurafenib and aldesleukin are approved by the FDA for the treatment of metastatic melanoma, the FDA has not yet approved the combination of vemurafenib and aldesleukin. Researchers have found that a large number of melanoma cells have mutations in the BRAF gene. It has been shown that vemurafenib blocks the effects of these mutations in the BRAF gene, and, as a result, may help to prevent cancer growth. Aldesleukin, also referred to as IL-2, is an immunotherapy drug administered via IV infusion that increases the growth of key cells within the immune system that are responsible for targeting cancer cells. Activating more of these key cells, called T-lymphocytes and natural-killer cells, leads to increased cancer cell death. The BRAF gene is located on a larger pathway called the MAPK pathway. Studies have shown that when a BRAF inhibitor, like vemurafenib is used to block the MAPK pathway, melanocytes, or cancer cells express more proteins on their surfaces, making them easier for T-lymphocytes and natural killer cells to recognize and kill them. This suggests that combining BRAF-targeted therapy with aldesleukin, which activates more of these white blood cells, can lead to an increase in the death of cancer cells. In this research study, we are looking to see whether the combination of vemurafenib, a BRAF-inhibitor combined with aldesleukin, an immunotherapy drug, work together to produce a better health outcome in people with metastatic melanoma.


Conducting Institutions:
Massachusetts General Hospital, Beth-Israel Deaconess Medical Center

Overall PI:
Jennifer Wargo, MD, Massachusetts General Hospital

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

Massachusetts General Hospital: Cancer Trials Call Center, 877-789-6100
Beth-Israel Deaconess Medical Center: Cancer Trials Call Center, 617-667-3060

Eligibility Criteria

Inclusion Criteria: - Histologically confirmed metastatic or unresectable melanoma with V600E mutation - Measurable disease - May have received prior immunotherapy (excluding interleukin 2) - Life expectancy greater than 3 months - Recovered from effects of previous surgery and/or traumatic injury - Must agree to use effective contraception Exclusion Criteria: - Pregnant or breastfeeding - Psychological, familial or other conditions that could hamper compliance with protocol - Receiving other study agents - History of carcinomatous meningitis - Known active brain metastases - Have received a BRAF inhibitor - Uncontrolled intercurrent illness - HIV positive on antiretroviral therapy - History of a different malignancy within past 5 years (except cervical cancer in situ or basal/squamous cell carcinoma of the skin) - Active hepatitis B or C - Have received allogenic bone marrow transplant or organ transplant
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