This phase 1 and 2 clinical trial recruiting in Lousiville, Kentucky will evaluate the safety of vemurafenib (Zelboraf) in combination with metformin (Glucophage) in advanced melanoma patients. The primary goal of phase 1 is to observe severe or life-threatening adverse events (grade 4) in 6 melanoma patients receiving vemurafenib with metformin. The primary goal of phase 2 will be to measure response to the treatment and overall survival (time from treatment until death from any cause).
The details
In advanced melanoma (stages 3 and 4), cancer spreads from the skin to other parts of the body. BRAF genes are often mutated in advanced melanoma. BRAF inhibitors such as vemurafenib block (inhibit) certain proteins in melanoma cells containing mutated BRAF genes. However, return of cancer after treatment with vemurafenib is common due to development of resistance. Metformin is a well-known drug for the treatment of type-2 diabetes. It has been found that metformin can overcome vemurafenib-resistance by inhibiting the same proteins. Therefore, a combination of vemurafenib and metformin could be an effective treatment in melanoma. However, adverse events associated with such treatment need to be evaluated.
Who are they looking for?
This study will recruit up to 55 patients with stage 3C or 4 unresectable (non-operable) melanoma with BRAF gene mutations. Ideal candidates should have normal liver, kidney, and blood functions. Pre-menopausal candidates should have negative pregnancy tests and should use birth control measures from the day of pregnancy testing to 90 days after the study.
Patients cannot take part in this study if they were treated with vemurafenib before. Pregnant or breast-feeding women cannot take part in this study. Patients cannot have uncontrolled infections, allergic reactions to metformin or other medical condition that could interfere with this study.
How will it work
In phase 1, 6 melanoma patients will be given 960 mg of oral vemurafenib daily. Oral metformin will be given in combination, first 500 mg twice daily for 2 weeks and then 850 mg twice daily. If 3 or more grade 4 or higher adverse events are observed among the 6 patients, the study will be halted.
If the study continues to phase 2, up to 55 patients will be treated with the same treatment combination as in phase 1, and response (such as tumor shrinkage) will be measured. Patients will be followed for up to 3 years following the end of treatment to determine overall survival rates.
