A Study to Determine Safety, Tolerability and Pharmacokinetics of Oral Dabrafenib In Children and Adolescent Subjects
Condition: Neoplasms, Brain
MeSH terms: Brain Neoplasms
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This was a 2-part, Phase I/IIa, multi-center, open label, study in pediatric and adolescent
      patients with advanced BRAF V600 mutation-positive solid tumors. Part 1 was a dose escalation
      study in patients with any BRAF V600 mutation-positive solid tumor using a modified Rolling 6
      Design (RSD). Part 2 was an expansion study to further evaluate the safety, tolerability, and
      clinical activity of dabrafenib in 4 tumor-specific pediatric populations. Patients
      participated in only either part 1 or part 2 of the study.
    

Detailed description: 
      Part 1 was a dose escalation study in subjects with any BRAF V600 mutation-positive solid
      tumor, designed to optimize efficiency of enrollment, minimize the number of subjects being
      treated at potentially sub-efficacious dose levels, and incorporating the evolving
      pharmacokinetic, safety and efficacy data from the adult development program. Dose escalation
      part of the study was to determine the maximum tolerated dose (MTD) and recommend the dose
      for phase 2 studies (RP2D). An MTD has not been identified for dabrafenib in the adult
      population. This does not preclude the identification of an MTD in the pediatric population.
      Modified RSD was employed to determine the MTD. Part 1 used dual criteria of dose limiting
      toxicity (DLT) and observed dabrafenib exposures to make decisions to advance to the next
      dose level. Target exposure criteria based on adults treated at the approved adult dose of
      300 mg (150 mg given BID) were observed in this study before meeting criteria for stopping
      dose escalation due to observations of DLTs, and served as the criteria for determining the
      RP2D for dabrafenib in pediatric subjects. Thus, MTD has not been established in pediatric
      population, similar to the previous dose finding efforts in adult subjects.

      Part 2 was a tumor specific expansion study to further evaluate the safety/tolerability
      profile and to discover possible clinical efficacy of dabrafenib in 4 tumor-specific
      pediatric populations known to have BRAFV600 activation: high grade glioma (HGG), low grade
      glioma (LGG), Langerhans cell histiocytosis (LCH), miscellaneous tumors including melanoma
      and papillary thyroid carcinoma (Other). The exposures for subjects dosed on the basis of
      weight were also evaluated by age categories.
    

Intervention name(s): Dabrafenib
Intervention type(s): Drug
Intervention description(s): Dabrafenib is available as 50 mg or 75 mg capsules and as oral suspension (10 mg/mL for subjects unable to swallow capsules). Dabrafenib (either formulation) will be administered orally as a single dose on Day 1 and twice daily from Day 2, based on weight at the appropriate study dose level.
Other intervention name(s): DRB436
Intervention MeSH terms: Dabrafenib
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Children and Adolescents; BRAF; dabrafenib; dose escalation; BRF116013; V600-mutation positive; BRF