A Study Comparing Trametinib and Dabrafenib Combination Therapy to Dabrafenib Monotherapy in Subjects With BRAF-mutant Melanoma - Full Text View

Purpose

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.

Condition	Intervention	Phase
Melanoma	Drug: dabrafenib plus trametinib Drug: dabrafenib plus trametinib placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Melanoma

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

Progression-free survival [ Time Frame: Up to 13 months ] [ Designated as safety issue: No ]
Progression-free survival defined as the time from randomization until the earliest date of disease progression or death due to any cause

Secondary Outcome Measures:

Overall survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
Overall survival defined as the time from randomization until death due to any cause
Overalll response rate [ Time Frame: Up to 13 months ] [ Designated as safety issue: No ]
Overalll response rate defined as the percentage of subjects with a confirmed complete response [CR] or partial response [PR] at any time per Response Evaluation Criteria in Solid Tumors [RECIST], version 1.1
Duration of response [ Time Frame: Up to 13 months ] [ Designated as safety issue: No ]
Duration of response defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause among subjects who achieve a confirmed response [i.e., confirmed CR or PR]

Enrollment:	340
Study Start Date:	May 2012
Estimated Study Completion Date:	May 2015
Estimated Primary Completion Date:	May 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Combination trametinib plus dabrafenib combination	Drug: dabrafenib plus trametinib dabrafenib 150 mg twice daily and trametinib 2 mg once daily
Active Comparator: Dabrafenib monotherapy trametinib placebo plus dabrafenib	Drug: dabrafenib plus trametinib placebo dabrafenib 150 mg twice daily and trametinib placebo

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01584648

Show 108 Study Locations

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

More Information

No publications provided

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT01584648 History of Changes
Other Study ID Numbers:	115306
Study First Received:	April 23, 2012
Last Updated:	April 25, 2013
Health Authority:	Australia: Human Research Ethics Committee United States: Food and Drug Administration Canada: Health Canada

Keywords provided by GlaxoSmithKline:

Randomized study
combination therapy
BRAF inhibitor
GSK1120212
BRAF V600E/K mutation-positive cutaneous melanoma

trametinib
GSK2118436
MEK inhibitor
Phase III
dabrafenib

Additional relevant MeSH terms:

Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on May 23, 2013