Phase 2 clinical trial evaluating the safety and efficacy of selumetinib and dacarbazine in patients with advanced melanoma

This phase 2 clinical trial investigated the safety and efficacy dacarbazine and selumetinib for the treatment of patients who had advanced melanoma with a BRAF mutation.  

The BRAF gene makes a protein called B-Raf which is involved in cell growth processes. Approximately 50% of patients with metastatic (cancer of the pigmented cells of the skin that has spread to distant organs and tissues) melanoma have mutations (defects) in the BRAF gene. This dysfunctional gene may play a part in the fast and uncontrolled growth of this form of cancer. As a result, treatment for these patients aims to block the action and signaling of the BRAF gene, thus preventing further growth and spreading of the melanoma. Selumetinib is a drug still undergoing clinical trials that has shown anti-cancer properties in patients with BRAF-mutated melanomas when combined with chemotherapy. Dacarbazine is a chemotherapy drug commonly used as the first treatment for patients with metastatic melanoma. This treatment is given intravenously and aims to destroy the cancer cells. 

This clinical trial included 91 patients with advanced melanoma from 12 countries. Patients were randomly assigned to receive either selumetinib twice a day for 21 days plus dacarbazine on the first day of the 21-days treatment cycle (45 patients), or a daily placebo (a substance with no medical effects used as a control when testing new drugs) plus dacarbazine on the first day of the cycle (46 patients). After an average follow up period of 1 year, results showed that selumetinib added to dacarbazine showed a 37% improvement in the length of time the without any disease progression (progression-free survival), compared to dacarbazine alone (5.6 months versus 3.0 months). Overall survival was also improved in the selumetinib group, though not significantly (by 7%). Although both treatment groups experienced side effects, these were slightly more common in patients receiving the combination of selumetinib and dacarbazine. The most common side effects reported were nausea, vomiting, diarrhea and skin reactions such as acne and rash.

Overall, this study showed that selumetinib plus dacarbazine is a well tolerated treatment and gives significantly increased progression free survival time for patients with advanced melanoma and a smaller benefit in overall survival.

This was a phase 2 clinical trial and included a very small number of participants. The follow up period was also too short to determine the real effects of this drug combination in advanced melanoma patients. Further clinical trials are expected in order to determine the safety and efficacy of selumetinib. Also, selumetinib is not yet approved by the U.S. FDA for the treatment of patients with melanoma.

This study was funded by AstraZeneca, the manufacturer of selumetinib.