This trial is active, not recruiting.

Condition melanoma
Treatments dabrafenib, vemurafenib, trametinib
Phase phase 3
Targets BRAF, MEK
Sponsor GlaxoSmithKline
Start date June 2012
End date September 2018
Trial size 704 participants
Trial identifier NCT01597908, 116513


This is a two-arm, open-label, randomised, Phase III study comparing dabrafenib (GSK2118436) and trametinib (GSK1120212) combination therapy to vemurafenib. Subjects with histologically confirmed cutaneous melanoma that is either stage IIIc (unresectable) or stage IV, and BRAF V600E/K mutation positive will be screened for eligibility. Subjects who have had prior systemic anti-cancer treatment in the advanced or metastatic setting will not be eligible although prior systemic treatment in the adjuvant setting will be allowed. Approximately 694 subjects will be randomised 1:1 (combination therapy:vemurafenib). The primary endpoint is overall survival (OS) for subjects receiving the combination therapy compared with those receiving vemurafenib.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
BRAF inhibitor plus MEK inhibitor
dabrafenib 150 mg twice daily po
trametinib 2 mg once daily po
(Active Comparator)
BRAF inhibitor
vemurafenib 960 mg twice daily po

Primary Outcomes

Overall Survival
time frame: From randomization until death due to any cause (up to Study Week 92)

Secondary Outcomes

Progression-free Survival, as Assessed by the Investigator
time frame: From randomization to the first documented occurrence of disease progression or death due to any cause (up to Study Week 80)
Overall Response, as Assessed by the Investigator
time frame: Screening, Week 8 and every 8 weeks thereafter through Week 56, and then every 12 weeks
Duration of Response, as Assessed by the Investigator
time frame: From the first documented evidence of a CR or PR until the earliest date of disease progression or death due to any cause (up to Study Week 80)

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - >= 18 years of age - Stage IIIc or Stage IV BRAF V600E/K cutaneous melanoma - Measurable disease according to RECIST 1.1 - Women of childbearing potential with negative serum pregnancy test prior to randomisation - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 - Adequate baseline organ function Exclusion Criteria: - Any prior use of a BRAF or MEK inhibitor - Prior systemic anti-cancer treatment in the advanced or metastatic setting; prior systemic treatment in the adjuvant setting is allowed - History of another malignancy (except subjects who have been disease free for 3 years or with a history of completely resected non-melanoma skin cancer) - Known HIV, HBV, HCV infection (except chronic or cleared HBV and HCV infection which will be allowed) - Brain metastases (except if all known lesions were previously treated with surgery or stereotactic radiosurgery and lesions, if still present, are confirmed stable for >= 12 weeks prior to randomisation or if no longer present are confirmed no evidence of disease for >= 12 weeks, and are asymptomatic with no corticosteroid requirements for >= 4 weeks prior to randomisation, and no enzyme inducing anticonvulsants for >= 4 weeks prior to randomisation - History or evidence of cardiovascular risk (LVEF < LLN; QTcB >= 480 msec; blood pressure or systolic >=140 mmHg or diastolic >= 90 mmHg which cannot be controlled by anti-hypertensive therapy) - History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)

Additional Information

Official title A Phase III, Randomised, Open-label Study Comparing the Combination of the BRAF Inhibitor, Dabrafenib and the MEK Inhibitor, Trametinib to the BRAF Inhibitor Vemurafenib in Subjects With Unresectable (Stage IIIc) or Metastatic (Stage IV) BRAF V600E/K Mutation Positive Cutaneous Melanoma
Trial information was received from ClinicalTrials.gov and was last updated in December 2014.
Information provided to ClinicalTrials.gov by GlaxoSmithKline.
Location data was received from the National Cancer Institute and was last updated in July 2016.