Dabrafenib With Trametinib in the Adjuvant Treatment of High-risk BRAF V600 Mutation-positive Melanoma (COMBI-AD).
brief summary
This was a two-arm, randomized, double-blind Phase III study of dabrafenib in combination with trametinib versus 2 placebos in the adjuvant treatment of melanoma after surgical resection. Patients with completely resected, histologically confirmed, BRAF V600E/K mutation-positive, high-risk (Stage IIIa \[lymph node metastasis \>1 mm\], IIIb or IIIc) cutaneous melanoma were screened for eligibility. Approximately 852 patients were planned to be randomized in a 1:1 ratio, stratified by BRAF mutation status (V600E, V600K) and stage of disease (Stage IIIa, IIIb, IIIc). Patients received either dabrafenib (150 milligram (mg) twice daily \[BID\]) and trametinib (2 mg once daily \[QD\]) combination therapy or 2 matching placebos (one each for dabrafenib and trametinib) for 12 months or until disease recurrence, death, unacceptable toxicity, or withdrawal of consent. Patients were followed for disease recurrence and survival during and after the treatment period. The study did not permit crossover. Doses of study treatment could be modified and/or interrupted for management of toxicities associated with study treatment.
detailed description
The study periods were follows:
1. Screening: Assessments were to be completed within 28 days of randomization. 2. Treatment: The treatment period was 12 months. Discontinuation of study treatment could occur earlier than 12 months for disease recurrence, death, unacceptable toxicity or withdrawal of consent. 3. Post treatment follow-up (before recurrence): Patients were to be followed for disease recurrence every 3 months after the end of treatment until Month 24, every 6 months after Month 24 and annually after Month 60 (365 days +/- 14 days from last visit). 4. Post treatment follow-up (after recurrence): After disease recurrence patients remained on study for follow-up assessments every 3 months until Month 24, every 6 months after Month 24, and annually after Month 60 (365 days +/- 14 days from last visit).
official title
COMBI-AD: A Phase III Randomized Double Blind Study of Dabrafenib (GSK2118436) in COMBInation With Trametinib (GSK1120212) Versus Two Placebos in the ADjuvant Treatment of High-risk BRAF V600 Mutation-positive Melanoma After Surgical Resection