Pharmacokinetics of Repeat Oral Doses of Dabrafenib and the Combination of Dabrafenib and Trametinib in Chinese Subjects With Melanoma

Sponsor
GlaxoSmithKline
Study ID
NCT02447939
Phase
PHASE1
Status
Withdrawn

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. Each capsule will contain 50 mg or 75 mg of free base (present as the mesylate salt).
  • Trametinib — DRUG
    Trametinib study will be provided as 0.5 mg and 2.0 mg tablets. Each tablet will contain 0.5 mg or 2.0 mg of trametinib parent (present as the DMSO solvate)

Study Details

Present clinical study will be conducted in China to evaluate the pharmacokinetics (PK) of single and repeat oral doses of dabrafenib alone and dabrafenib and trametinib in combination, the safety profile and the clinical activity of dabrafenib in combination with trametinib in Chinese melanoma subjects with BRAF V600E/K mutation. Approximately 20 evaluable subjects will be enrolled in the study, out of which, the first 10 subjects will be enrolled into cohort A (Part I and II) and remaining 10 subjects will be enrolled in cohort B. Subjects in cohort A (Part I) will receive dabrafenib 150 mg twice daily (BID) and subjects in cohort A (Part II) and Cohort B will receive combination of dabrafenib 150 mg BID and trametinib 2 mg once daily (QD). Study treatment will continue until disease progression, death or unacceptable toxicity. After disease progression, all enrolled subjects will be followed up for overall survival. The study will be completed after all subjects have died or surviving subjects have had at least 5 years of follow-up, whichever occurs first.

Key Dates

Start date
May 31, 2017
Status verified
Jan 2017
Primary completion
Oct 31, 2018
Completion
Dec 31, 2018

Study Design

Enrollment
0 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Dabrafenib and Trametinib
    Subject will be assigned in 2 cohorts, in cohort A, subjects will be administered dabrafenib (150 mg BID) monotherapy from Day1 to Day 21 (first part), followed by dabrafenib (150 mg BID) and trametinib (2mg QD) combination (second part, starting from day 22). After the last subject in cohort A has finished the last pharmacokinetic sampling(1st part ), another 10 subjects will be enrolled in cohort B with administration of dabrafenib (150 mg BID) in combination with oral trametinib (2mg QD).

Primary Outcome Measure

Composite of PK parameters of dabrafenib and its metabolites following single and repeat dabrafenib (150 mg BID) dose: Cmax,Tmax and AUC(0-tau) [ Time Frame: At Day 1: Pre dose, 1,2, 3, 4, 6, 8, 12 and 24 h post dose. ]

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