MEK115306 A study of dabrafeniib, trametinib & combination in melanoma
Research type
Research Study
Full title
A Phase III, randomized, double-blinded study comparing the combination of the BRAF inhibitor, dabrafenib and the MEK inhibitor, trametinib to dabrafenib and placebo as first-line therapy in subjects with unresectable (Stage IIIC) or metastatic (Stage IV) BRAF V600E/K mutation-positive cutaneous melanoma
IRAS ID
99579
Contact email
Sponsor organisation
Novartis Pharma AG
Eudract number
2011-006087-49
Clinicaltrials.gov Identifier
102,175, Investigational New Drug (IND) Number
Duration of Study in the UK
3 years, 0 months, 0 days
Research summary
Melanoma is the most aggressive form of skin cancer. Worldwide, approximately 37,000 people die of the disease 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 another, as yet unlicensed, treatment for melanoma, which have been shown to be effective given alone.
This study seeks to demonstrate that when a BRAFi (dabrafenib) is given in combination with a MEKi(trametinib), more subjects experience a more prolonged and profound response to treatment than with BRAFi alone. In this study, subjects with confirmed skin melanoma, which is advanced or has spread to other parts of the body will be assessed to see if they are suitable to take part in the study. Patients will have a test on a small piece of tumour tissue (usually archival) for V600 B-Raf mutation. Such tissue is sensitive to the agents in the study. Up to sixty percent of melanoma patients fall into this category. Approximately 340 subjects will be allocated randomly to treatment with dabrafenib/trametinib in combination or dabrafenib alone. Subjects in the dabrafenib only arm will receive dabrafenib with a placebo (inactive medicine looking like trametinib). In the combination treatment arm dabrafenib will be dosed at 150mg twice daily and trametinib at 2mg once per day. The benefit of the combination of dabrafenib and trametinib over dabrafenib alone will be judged by comparing the effect on the time the patient's disease does not get worse (progression free survival). This endpoint will be confirmed by an independent review committee. After treatment discontinuation, subjects will be followed to measure the effect on lifespan.REC name
North West - Liverpool Central Research Ethics Committee
REC reference
12/NW/0263
Date of REC Opinion
2 May 2012
REC opinion
Further Information Favourable Opinion