Phase II Biomarker Study Comparing the Combination of BRAF Inhibitor Dabrafenib With MEK Inhibitor Trametinib Versus the Combination After Monotherapy With Dabrafenib or Trametinib

Sponsor
GlaxoSmithKline
Study ID
NCT02314143
Phase
PHASE2
Status
Terminated

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Dabrafenib — DRUG
    Dabrafenib will be provided as 50 mg and 75 mg capsules.
  • Trametinib — DRUG
    Trametinib study medication will be provided as 0.5 mg and 2.0 mg tablets.

Study Details

This is a three-arm, open-label, randomised Phase II study to evaluate whether the different sequencing of dabrafenib and trametinib monotherapies and the upfront combination has an impact on translational or clinical activity in subjects with BRAF mutant metastatic unresectable stage IIIc or IV melanoma. Both dabrafenib and trametinib have demonstrated clinical activity as monotherapies and in combination in BRAF-mutant melanoma. However, duration of responses seem to be limited due to acquired drug resistance. The goal of this protocol is to study the sequential effects of BRAF and MEK inhibition on skin, blood and tumour biomarkers and to study the correlation between biomarkers and response to treatment and intrapatient toxicity. Approximately 54 eligible subjects will be randomised in the ratio of 1:1:1 to one of the three treatment arms.

Key Dates

Start date
Nov 13, 2013
Status verified
Sep 2018
Primary completion
Jan 19, 2017
Completion
Jan 19, 2017

Study Design

Enrollment
48 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC

Arms

  • Experimental: Dabrafenib followed by combination therapy
    Eligible subjects will receive dabrafenib 150 milligrams (mg) twice a day (BID) continuously during 8 weeks of monotherapy treatment followed by the combination of trametinib 2 mg once daily with dabrafenib 150 mg BID until disease progression, death or unacceptable toxicity.
  • Experimental: Trametinib followed by combination therapy
    Eligible subjects will receive trametinib 2 mg per day continuously during 8 weeks of monotherapy treatment followed by the combination of trametinib 2 mg once daily with dabrafenib 150 mg BID until disease progression, death or unacceptable toxicity.
  • Experimental: Combination therapy
    Eligible subjects will receive trametinib 2 mg per day plus dabrafenib 150 mg BID continuously until disease progression, death or unacceptable toxicity.

Primary Outcome Measure

Number of Participants With Percentage Change From Baseline in Extracellular Signal-regulated Kinase (ERK) Phosphorylation (p-ERK) H Score From Week 0 to Week 2 [ Time Frame: Baseline (Week 0) and up to 2 weeks ]

Related Studies