Last updated: 11/07/2018 09:09:50
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 GSK Clinical Study Register is no longer maintained for this study.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, randomized, double-blinded study comparing the combination of the BRAF inhibitor, dabrafenib and the MEK inhibitor, trametinib to dabrafenib and placebo as first-line therapy in subjects with unresectable (Stage IIIC) or metastatic (Stage IV) BRAF V600E/K mutation-positive cutaneous melanoma
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, randomized, double-blinded study comparing the combination of the BRAF inhibitor, dabrafenib and the MEK inhibitor, trametinib to dabrafenib and placebo as first-line therapy in subjects with unresectable (Stage IIIC) or metastatic (Stage IV) BRAF V600E/K mutation-positive cutaneous melanoma
Trial description: This is a two-arm, double-blinded, randomized, Phase III study comparing dabrafenib (GSK2118436) and trametinib (GSK1120212) combination therapy to dabrafenib administered with a trametinib placebo (dabrafenib monotherapy). 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 340 subjects will be randomized 1:1 (combination therapy: dabrafenib monotherapy). Subjects will be stratified by lactate dehydrogenase (LDH) level (> the upper limit of normal (ULN) versus less than or equal to the ULN) and BRAF mutation (V600E versus V600K). The primary endpoint is investigator-assessed, progression-free survival for subjects receiving the combination therapy compared with those receiving dabrafenib monotherapy. Subjects will be followed for overall survival; crossover will not be permitted.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Progression-Free Survival (PFS) as assessed by the investigator
Timeframe: From randomization until the earliest date of disease progression (PD) or death due to any cause (average of 9 study months)
Secondary outcomes:
Overall Survival (OS)
Timeframe: From randomization until death due to any cause (average of 9 study months)
Number of participants with a confirmed response (complete response or partial response)
Timeframe: From randomization until the first documented complete response or partial response (average of 9 study months)
Duration of response for participants with a confirmed response (complete response or partial response)
Timeframe: From the time of the first documented response (CR or PR) until disease progression (average of 9 study months)
Number of participants with any adverse event (AE) or serious adverse event (SAE)
Timeframe: From the time the first dose of study treatment administered until 30 days after discontinuation of study treatment (average of 9 study months)
Number of participants with a worst-case on-therapy grade change from Baseline to Grade 3 and 4 for the indicated clinical chemistry parameters
Timeframe: From Baseline up to Week 64
Number of participants with a worst-case on-therapy grade change from Baseline to Grade 3 and 4 for the indicated hematology parameters
Timeframe: From Baseline up to Week 64
Number of participants with a worst-case on-therapy change from Baseline with respect to the normal range for the indicated hematology parameters
Timeframe: From Baseline up to Week 64
Number of participants with a worst-case on-therapy change from Baseline with respect to the normal range for the indicated clinical chemistry parameters
Timeframe: From Baseline up to Week 64
Number of participants with a worst-case on-therapy change from Baseline in heart rate
Timeframe: From Baseline up to Week 64
Number of participants with a worst-case on-therapy change from Baseline in systolic and diastolic blood pressure to Grade 2 or Grade 3
Timeframe: From Baseline up to Week 64
Number of participants with a worst-case on-therapy change from Baseline in temperature
Timeframe: From Baseline up to Week 64
Number of participants with a worse-case on-therapy change from Baseline in the Bazett's QTc to Grade 2 or Grade 3
Timeframe: From Baseline up to Week 60
Number of participants with worst-case on-therapy change from Baseline in Left Ventricular Ejection Fraction (LVEF) as assessed by echocardiogram
Timeframe: From Baseline up to Week 60
Number of participants with incidence of squamous cell carcinoma
Timeframe: From Baseline up to end of study (average of 9 study months)
Plasma concentrations of trametinib
Timeframe: Week 8: pre-dose, 1-3 hours and 4-6 hours post dose; Week 16 pre-dose and Week 24 pre-dose
Plasma Concentrations of dabrafenib and its metabolites
Timeframe: Week 8: pre-dose, 1-3 hours and 4-6 hours post dose; Week 16 pre-dose and Week 24 pre-dose
Interventions:
Enrollment:
422
Primary completion date:
2013-26-08
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Long GV, Stroiakovski D, Gogas H, Levchencko E, de Braud F, Larkin J, Garbe C, Jouary T, Hauschild A, Grob J, Chiarion-Sileni V, Lebbe C, Mandalà M, Millward M, Arance Fernández A, Bondarenko I, Haanen JBAG, Hansson J, Utikal J, Ferraresi V,...Flaherty K.Combined BRAF and MEK Inhibition Versus BRAF Inhibition Alone in Melanoma.N Engl J Med.2014;371:1877-1888
Schadendorf D, Amonkar MM, Stroyakovskiy D, Levchenko E, Gogas H, de Braud F, Grob JJ, Bondarenko I, Garbe C, Lebbe C, Larkin J, Chiarion-Sileni V, Millward M, Arance A, Mandalà M, Flaherty KT, Nathan P, Ribas A, Robert C, Casey M, DeMarini DJ....Health-related quality of life impact in a randomized phase III study of the combination of dabrafenib and trametinib versus dabrafenib monotherapy in patients with BRAF V600 metastatic melanoma .Eur J Cancer.2015;51(7):833-840
Medical condition
Melanoma
Product
dabrafenib, dabrafenib/trametinib, trametinib
Collaborators
Not applicable
Study date(s)
May 2012 to January 2018
Type
Interventional
Phase
2/3
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
none
- 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
- 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.)
Inclusion and exclusion 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
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
2013-26-08
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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