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

Status:	Active, not recruiting
Conditions:	Skin Cancer
Therapuetic Areas:	Oncology
Healthy:	No
Age Range:	18 - Any
Updated:	8/16/2018
Start Date:	May 4, 2012
End Date:	October 15, 2018

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

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.

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

We found this trial at

sites

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

Use our guide to learn which trials are right for you!

Select your condition

Common Conditions

All Conditions