This trial is active, not recruiting.

Condition melanoma
Treatments aldesleukin, vemurafenib
Phase phase 2
Target BRAF
Sponsor Massachusetts General Hospital
Start date January 2013
End date February 2015
Trial size 49 participants
Trial identifier NCT01754376, 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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Oral vemurafenib twice a day IV infusion of aldesleukin
aldesleukin Interleukin 2
Intravenous therapy given every 8 hours for up to 14 doses per week.
vemurafenib Zelboraf
Tablets given twice daily.

Primary Outcomes

Efficacy of Vemurafenib + Aldesleukin
time frame: 2 years

Secondary Outcomes

Determine Response Rates (Complete, Partial and Durable)
time frame: 2 years
Overall Survival
time frame: 2 years
Toxicity and Safety of Aldesleukin and Vemurafenib
time frame: 2 years
Confirm Pre-Clinical Data
time frame: 2 years
Exploration of Biomarkers
time frame: 2 years

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title COMBAT 1: A Phase II Trial of Combined BRAF-Targeted Therapy and Immunotherapy for Melanoma
Principal investigator Ryan J Sullivan, MD
Description You will take oral vemurafenib twice a day for 2 weeks. Following this lead-in period, you will receive aldesleukin via IV infusion on Day 15 of the study. One course of aldesleukin is 12 weeks long; you will receive aldesleukin via IV infusion every 8 hours for the first five days. Youi will be hospitalized for the 5 days that you are receiving aldesleukin. This week that you are hospitalized will be referred to as Week 1. Week 1 of aldesleukin will be days 15-19 (M-F) of the 12 week cycle. Following Week 1 of therapy, you will be discharged from the hospital and only take vemurafenib at home for the following week. You wil then come in for one more week of aldesleukin during days 29-33 of the 12 week cycle. This is referred to as Week 2 of aldesleukin. You will continue to take vemurafenib twice daily during the course of aldesleukin. Your cancer will be evaluated at screening and at Week 12 following the beginning of the first aldesleukin course with a CT scan. After the first cycle, your tumor will be evaluated every 8 weeks for the first year, then every 12 weeks for years 2 and 3, every 6 months for year 5, and annually thereafter. During the research study, you will come into the clinic weekly for various tests and procedures. If scans show that your cancer has improved after the first course of aldesleukin, your doctor may allow you to continue on the a second course. In the event of a second course of aldesleukin, you will remain on vemurafenib throughout the second course. If your doctor decides you will not receive a second course of aldesleukin, you may still remain on vemurafenib until one of the following events occurs: Your cancer becomes worse, you experience serious side effects that are from taking vemurafenib, you request to discontinue taking vemurafenib/withdraw from the study, you develop another illness that prevents you from being able to take vemurafenib, the study is terminated by the sponsor or your study doctor decides it is in your best interest to discontinue treatment with vemurafenib. In some cases if your cancer does get worse, but you and your study doctor believe you are still benefitting from vemurafenib in some way, you may continue receiving it after you consult with the study director. After the final dose of the study drug we would like to keep track of your medical condition for the rest of your life. We would like to do this by calling you on the telephone once a year to see how you are doing. Keeping in touch with you and checking your condition every year helps us look at the long-term effects of the research study.
Trial information was received from ClinicalTrials.gov and was last updated in March 2016.
Information provided to ClinicalTrials.gov by Massachusetts General Hospital.