Overview

This trial is active, not recruiting.

Condition melanoma
Treatments dabrafenib, trametinib, placebos
Phase phase 3
Targets BRAF, MEK
Sponsor GlaxoSmithKline
Start date January 2013
End date December 2017
Trial size 852 participants
Trial identifier NCT01682083, 115532

Summary

This is 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 will be screened for eligibility. Subjects will be 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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Experimental)
Subjects will receive dabrafenib (150 mg twice daily) and trametinib (2 mg once daily) orally for 12 months.
dabrafenib
Each capsule contains 50 mg or 75 mg of free base (present as the mesylate salt)
trametinib
Each tablet contains 0.5 mg or 2.0 mg of trametinib parent (present as the DMSO solvate)
(Placebo Comparator)
Subjects will receive matching placebos orally for 12 months
placebos
The placebo capsules and tablets contain the same inactive ingredients and film coatings as the dabrafenib and trametinib study treatment

Primary Outcomes

Measure
Relapse-free survival (RFS)
time frame: Approximately 32 months

Secondary Outcomes

Measure
Overall survival (OS) of dabrafenib and trametinib as a combination therapy versus placebo
time frame: approximately 5 years
Distant metastasis-free survival (DMFS) of dabrafenib and trametinib as a combination therapy versus placebo
time frame: approximately 32 months
Freedom from relapse (FFR) of dabrafenib and trametinib as a combination therapy versus placebo
time frame: approximately 32 months
Safety of dabrafenib and trametinib as a combination therapy in the overall study population
time frame: approximately 5 years

Eligibility Criteria

Male or female participants at least 18 years old.

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. 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)

Additional Information

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
Trial information was received from ClinicalTrials.gov and was last updated in December 2016.
Information provided to ClinicalTrials.gov by GlaxoSmithKline.