A Study Comparing Trametinib and Dabrafenib Combination Therapy to Dabrafenib Monotherapy in Subjects With BRAF-mutant Melanoma
Condition: Melanoma
MeSH terms: Melanoma
Intervention: Dabrafenib; Trametinib; Trametinib placebo
Intervention description: Dabrafenib 150 mg twice daily; Trametinib 2 mg once daily; Dabrafenib 150 mg twice daily and trametinib placebo
Intervention MeSH terms: Trametinib; Dabrafenib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 423.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Randomized study; combination therapy; BRAF inhibitor; GSK1120212; BRAF V600E/K mutation-positive cutaneous melanoma; trametinib; GSK2118436; MEK inhibitor; Phase III; dabrafenib

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed cutaneous melanoma that is either Stage IIIC (unresectable)
             or Stage IV (metastatic), and determined to be BRAF V600E/K mutation-positive using
             the bioMerieux (bMx) investigational use only (IUO) THxID BRAF Assay (IDE: G120011).
             The assay will be conducted by a central reference laboratory. Subjects with ocular or
             mucosal melanoma are not eligible.

          -  The subject must have a radiologically measurable tumor

          -  The subject is able to carry out daily life activities without significant difficulty
             (ECOG performance status score of 0 or 1).

          -  Able to swallow and retain oral medication

          -  Sexually active subjects must use acceptable methods of contraception during the
             course of the study

          -  Adequate organ system function and blood counts

        Exclusion Criteria:

          -  Prior treatment with a BRAF or a MEK inhibitor

          -  Prior systemic anti-cancer treatment for Stage IIIC (unresectable) or Stage IV
             (metastatic) melanoma. Prior systemic treatment in the adjuvant setting is allowed.
             (Note: Ipilimumab treatment must end at least 8 weeks prior to randomization.)

          -  The subject has received major surgery or certain tyes of cancer therapy with 21 days
             of starting treatment

          -  Current use of prohibited medication listed in the protocol

          -  Left ventricular ejection fraction less than the lower limit of normal

          -  Uncontrolled blood pressurl

          -  History or current evidence of retinal vein occlusion or central serous retinopathy

          -  Brain metastases unless previously treated with surgery or stereotactic radiosurgery
             and the disease has been stable for at least 12 weeks

          -  The subject is pregnant or nursing