Last updated: 11/07/2018 10:33:08
This product has been transferred to Novartis. GSK Clinical Study Register is no longer maintained for this study. The most up to date information is available on clinicaltrials.gov
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 melanomaCOMBI-v
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
No longer a GSK study
No longer a GSK study
Trial overview
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 description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
Overall survival
Timeframe: From randomization until death due to any cause (up to Study Week 92)
Secondary outcomes:
Progression-free survival, as assessed by the Investigator
Timeframe: 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
Timeframe: Screening, Week 8 and every 8 weeks thereafter through Week 56, and then every 12 weeks
Duration of response, as assessed by the Investigator
Timeframe: 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)
Interventions:
Enrollment:
704
Primary completion date:
2014-17-04
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Robert,Karaszewska,Schachter,Rutkowski,Mackiewicz,Stroiakovski,Lichinitser,Dummer,Grange,Mortier,Chiarion-Sileni,Drucis,Krajsova,Hauschild,Lorigan,Wolter,Long,Flaherty,Nathan,Ribas,Martin,Sun,Crist,Legos,Rubin,Little,Schadendorf.Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametinib.N Engl J Med.2015;372:30-39
Medical condition
Melanoma
Product
dabrafenib, dabrafenib/trametinib, trametinib, vemurafenib
Collaborators
Not applicable
Study date(s)
June 2012 to September 2018
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
none
- >= 18 years of age
- Stage IIIc or Stage IV BRAF V600E/K cutaneous melanoma
- 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
Inclusion and exclusion criteria
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)
Trial location(s)
This study does not involve prospective enrollment of participants.
Study documents
Scientific result summary
Available language(s): English
Protocol
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
No longer a GSK study
Actual primary completion date
2014-17-04
Actual study completion date
Not applicable
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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