Overview

This trial is active, not recruiting.

Condition melanoma
Treatments dabrafenib plus trametinib, dabrafenib plus trametinib placebo
Phase phase 3
Sponsor GlaxoSmithKline
Start date May 2012
End date August 2013
Trial size 423 participants
Trial identifier NCT01584648, 115306

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
trametinib plus dabrafenib combination
dabrafenib plus trametinib
dabrafenib 150 mg twice daily and trametinib 2 mg once daily
(Active Comparator)
trametinib placebo plus dabrafenib
dabrafenib plus trametinib placebo
dabrafenib 150 mg twice daily and trametinib placebo

Primary Outcomes

Measure
Progression-Free Survival (PFS) as assessed by the investigator
time frame: From randomization until the earliest date of disease progression (PD) or death due to any cause (average of 9 study months)

Secondary Outcomes

Measure
Overall Survival (OS)
time frame: 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)
time frame: 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)
time frame: 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)
time frame: 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
time frame: 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
time frame: 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
time frame: 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
time frame: From Baseline up to Week 64
Number of participants with a worst-case on-therapy change from Baseline in heart rate
time frame: 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
time frame: From Baseline up to Week 64
Number of participants with a worst-case on-therapy change from Baseline in temperature
time frame: 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
time frame: 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
time frame: From Baseline up to Week 60
Number of participants with incidence of squamous cell carcinoma
time frame: From Baseline up to end of study (average of 9 study months)
Plasma concentrations of trametinib
time frame: 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
time frame: Week 8: pre-dose, 1-3 hours and 4-6 hours post dose; Week 16 pre-dose and Week 24 pre-dose

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

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 information was received from ClinicalTrials.gov and was last updated in April 2014.
Information provided to ClinicalTrials.gov by GlaxoSmithKline.