Conditions: Melanoma
Keywords: Randomized study combination therapy BRAF inhibitor GSK1120212 BRAF V600E/K mutation-positive cutaneous melanoma trametinib GSK2118436 MEK inhibitor Phase III dabrafenib
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 423
Healthy volunteers: no

Brief summary:
This was a two-arm, double-blinded, randomized, Phase III study comparing dabrafenib and trametinib combination therapy to dabrafenib administered with a placebo (dabrafenib monotherapy). Subjects with histologically confirmed cutaneous melanoma that is either Stage IIIC (unresectable) or Stage IV, and BRAF V600E/K mutation positive were screened for eligibility. Subjects who had prior systemic anti-cancer treatment in the advanced or metastatic setting were not eligible although prior systemic treatment in the adjuvant setting was allowed. Subjects were stratified according to the baseline lactate dehydrogenase level and BRAF genotype.

Detailed description:
Dabrafenib and trametinib was administered orally at their recommended monotherapy doses of 150 mg b.i.d and 2 mg q.d., respectively. Subjects in the combination therapy arm received both agents; subjects in the dabrafenib monotherapy arm received dabrafenib and placebo. Treatment was continued in both arms until disease progression, death, unacceptable toxicity, or withdrawal of consent.

After treatment discontinuation, subjects were followed for survival and disease progression as applicable to collect data for the secondary objective of overall survival (OS).

Crossover to the combination therapy arm was allowed for subjects still receiving study treatment on the dabrafenib monotherapy arm after the positive result for the final OS analysis.

Arms:
arm 1: Dabrafenib and Trametinib combination arm 2: Dabrafenib and Trametinib placebo

Interventions: intervention 1: Dabrafenib intervention 2: Trametinib intervention 3: Trametinib placebo
Intervention descriptions: intervention 1: Dabrafenib 150 mg twice daily intervention 2: Trametinib 2 mg once daily intervention 3: Dabrafenib 150 mg twice daily and trametinib placebo

Protocol document: