Basic Trial Information
Trial Description
     Summary
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

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.

Eligibility 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 Contact Information

Trial Lead Organizations/Sponsors

GlaxoSmithkline

GSK Clinical Trials

Study Director

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01584648
Information obtained from ClinicalTrials.gov on April 29, 2013

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