Study of Dabrafenib +/- Trametinib in Combination With Ipilimumab for V600E/K Mutation Positive Metastatic or Unresectable Melanoma

Part of paid clinical trials in Los Angeles, California.

Sponsor
GlaxoSmithKline
Study ID
NCT01767454
Phase
PHASE1
Status
Completed

Conditions

  • Solid Tumours

Eligibility Criteria

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

Interventions

  • Dabrafenib — DRUG
    Dabrafenib 100 mg or 150 mg BID orally will be administered. Capsules with unit dose strengths of 50 mg or 75 mg
  • Trametinib — DRUG
    Trametinib 1 mg or 2 mg once daily will be administered. Tablets with unit dose strengths of 0.5 mg or 2 mg
  • Ipilimumab — DRUG
    Ipilimumab 3 mg/kg intravenously over 90 minutes Q3W for a total of 4 doses will be administered. Supplied as Vials of 50 mg/10 mL (5 mg/mL) and 200 mg/40 mL (5 mg/mL)

Study Details

This is an open-label, multi-center, dose-finding Phase 1 study that will enroll subjects at least 18 years old with unresectable or metastatic melanoma and BRAF V600 mutations. The primary objective of the study is to describe the safety for the doublet therapy (dabrafenib and ipilimumab) and the triplet therapy (dabrafenib/trametinib and ipilimumab). Preliminary efficacy data will also be collected. Subjects will be assigned to receive either the doublet combination (dabrafenib and ipilimumab) or the triplet combination (dabrafenib, trametinib, and ipilimumab). Subjects will be enrolled to dose-finding cohorts in the doublet combination (dabrafenib + ipilimumab) in a sequential 3+3 fashion. Following establishment of a dose for the doublet combination, an expansion cohort will be opened. At the same time, enrollment to dose finding cohorts for the triplet combination (dabrafenib + trametinib + ipilimumab) will begin in a sequential 6+6 fashion. Enrollment into triplet cohorts will take priority when both the doublet expansion arm and the triplet dose-finding arm are open for enrollment at the same time. Approximately 9-24 subjects will be enrolled to the dose finding portion of the study. Approximately 30 subjects will be enrolled to doublet expansion cohort and 30 subjects will be enrolled in the triplet expansion cohort. A two-week run-in period without ipilimumab will be followed by 4 intravenous doses of ipilimumab at the recommended dose and schedule. Oral daily dosing of dabrafenib or dabrafenib + trametinib will continue from the two-week run-in, through combination with ipilimumab, and post-ipilimumab until no longer of clinical benefit, in the opinion of the treating physician, or until unacceptable AE or death

Key Dates

Start date
Feb 12, 2013
Status verified
Nov 2017
Primary completion
Sep 4, 2015
Completion
Sep 4, 2015

Study Design

Enrollment
38 participants (actual)
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Doublet arm
    Subjects will be started with dabrafenib 150 mg twice daily (BID) orally for 2 weeks (run-in). The doublet arm will comprise 2 cohorts. Cohort A1 (Dabrafenib 150 mg BID + ipilimumab). Cohort A-1 (Dabrafenib 100 mg BID +ipilimumab). Ipilimumab will be administered as 3 mg/kg every 3 weeks (Q3W) for a total of 4 infusions over approximately 12-16 weeks. Dabrafenib will be continued through combination with ipilimumab and post-ipilimumab until no longer of clinical benefit, in the opinion of the treating physician, or until unacceptable AE or death
  • Experimental: Triplet arm
    This arm will be initiated using dabrafenib and ipilimumab doses established in the doublet dose-finding. Subjects will be started with dabrafenib and trametinib orally for 2 weeks (run-in), followed by ipilimumab 3 mg/kg Q3W for a total of 4 infusions over approximately 12-16 weeks. The triplet arm will comprise 3 planned cohorts. Cohort B-1: Dabrafenib 100 mg BID + trametinib 1 mg once daily + ipilimumab, Cohort B1: Dabrafenib 150 mg BID + trametinib 1 mg once daily+ ipilimumab, Cohort B2: Dabrafenib 150 mg BID + trametinib 2 mg once daily + ipilimumab. Dabrafenib and trametinib wil be continued through combination with ipilimumab and post-ipilimumab until no longer of clinical benefit, in the opinion of the treating physician, or until unacceptable AE or death

Primary Outcome Measure

Number of subjects with Adverse Events (AEs) to assess the safety of dabrafenib +/- trametinib when administered in combination with ipilimumab [ Time Frame: Follow-up up to 6 months after last subject last dose ]

Locations (7)

FacilityCityStateZIPSite coordinators
GSK Investigational SiteLos AngelesCalifornia90025-
GSK Investigational SiteSan FranciscoCalifornia94115-
GSK Investigational SiteBostonMassachusetts02215-
GSK Investigational SiteSt LouisMissouri63110-
GSK Investigational SiteNew YorkNew York10065-
GSK Investigational SiteNashvilleTennessee37232-
GSK Investigational SiteHoustonTexas77030-

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