MEK116513 Dabrafenib plus trametinib vs vemurafinib in melanoma
Research type
Research Study
Full title
A phase III, randomised, open-label study comparing the combination of the BRAF inhibitor, dabrafenib and the MEK inhibitor, trametinib to the BRAF inhibitor vemurafenib in subjects with unresectable (stage IIIc) or metastatic (stage IV) BRAF V600E/K mutation positive cutaneous melanoma
IRAS ID
105638
Contact name
Egle Sungailaite
Contact email
Sponsor organisation
Novartis Pharma AG
Eudract number
2011-006088-23
Duration of Study in the UK
2 years, 6 months, 0 days
Research summary
Worldwide, approximately 37,000 people die of malignant melanoma annually. Recently, two drugs, a "BRAF inhibitor" (BRAFi) and an immunotherapy, have been licensed for treatment of patients with melanoma which has spread and cannot be removed by surgery. Unfortunately, neither of these drugs is curative and after the initial response, the disease progresses rapidly with BRAFi treatment alone. "MEK inhibitors" (MEKi) are as yet unlicensed, treatment for melanoma, which have been shown to be effective given alone.
This study seeks to demonstrate the superiority of the combination of dabrafenib (BRAFi) + trametinib (MEKi ) , compared to vermurafinib (BRAFi ) given alone. After Informed Consent, patients will have a test on a small piece of their tumour tissue for a mutation known as the V600 BRAF mutation which helps to select patients whose cancer is most likely to respond to the study drugs. Up to sixty percent of melanomas fall into this category. Approximately 694 subjects globally will be allocated between the two treatment arms, and both Investigators and patients will know what treatment they are receiving . In the combination treatment arm, dabrafenib and trametinib will be given orally at their recommended doses: dabrafenib 150mg twice daily and trametinib at 2mg once per day. Vemurafenib will be given at 960mg orally twice a day.Patients will continue treatment until disease progression, death, unacceptable toxicity, or withdrawal of consent. The benefit of the combination of dabrafenib and trametinib over vemurafenib alone will be judged by comparing Overall Survival i.e. the time a patient survives whilst on treatment. The study will end when enough patients have died to statistically analyse the difference between the 2 treatment arms. Patients still alive at the end of the study will have the option to continue to receive their treatment in a roll over study.
REC name
North West - Haydock Research Ethics Committee
REC reference
12/NW/0427
Date of REC Opinion
14 Jun 2012
REC opinion
Favourable Opinion