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.
(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
19
sites
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Novartis Novartis, which was created in 1996 by the merger of the Swiss companies Ciba-Geigy...
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