Dabrafenib With Trametinib in the Adjuvant Treatment of High-risk BRAF V600 Mutation-positive Melanoma (COMBI-AD).
Condition: Melanoma
MeSH terms: Melanoma
Intervention: Dabrafenib; Trametinib; Placebos
Intervention description: Each capsule contained 50 mg or 75 mg of free base (present as the mesylate salt); Each tablet contained 0.5 mg or 2.0 mg of trametinib parent (present as the DMSO solvate); The placebo capsules and tablets contained the same inactive ingredients and film coatings as the dabrafenib and trametinib study treatment
Intervention MeSH terms: Trametinib; Dabrafenib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 870.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: MEK inhibitor; trametinib; Oncology; adjuvant melanoma; dabrafenib; dabrafenib and trametinib combination therapy; BRAF mutation-positive melanoma; BRAF inhibitor

Summary:

      This was a two-arm, randomized, double-blind Phase III study of dabrafenib in combination
      with trametinib versus two 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. Subjects were randomized to receive either
      dabrafenib (150 milligram (mg) twice daily [BID]) and trametinib (2 mg once daily [QD])
      combination therapy or two placebos for 12 months.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Completely resected histologically confirmed high-risk [Stage IIIa (LN metastasis more
             than 1 mm), IIIb or IIIc cutaneous melanoma determined to be V600E/K mutation positive
             by a central laboratory. Patients presenting with initial resectable lymph node
             recurrence after a diagnosis of Stage I or II melanoma are eligible.

          -  Surgically rendered free of disease no more than 12 weeks before randomization.

          -  Recovered from definitive surgery (e.g. no uncontrolled wound infections or indwelling
             drains).

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.

          -  Adequate hematologic, hepatic, renal and cardiac function.

        Key Exclusion Criteria:

          -  Known mucosal or ocular melanoma or the presence of unresectable in-transit
             metastases.

          -  Evidence of distant metastatic disease.

          -  Prior systemic anti-cancer treatment and radiotherapy for melanoma; prior surgery for
             melanoma is allowed.

          -  History of another malignancy or concurrent malignancy including prior malignant
             melanoma. Exceptions to this include: Patients who have been disease-free for 5 years
             or patients with a history completely resected non-melanoma skin cancer or
             successfully treated in situ carcinoma are eligible, for example cervical cancer in
             situ, atypical melanocytic hyperplasia or melanoma in situ, multiple primary
             melanomas, or other malignancies for which the patient has been disease free for > 5
             years.

          -  History or current evidence of cardiovascular risk.

          -  History or current evidence of retinal vein occlusion (RVO) or central serous
             retinopathy (CSR)