What is the purpose of this study?
This is a
2-part, study to determine the safety, tolerability and pharmacokinetics of
oral dabrafenib in pediatric subjects with advanced BRAF
mutation-positive solid tumors. Part 1 (dose escalation study) will identify
the recommended Part 2 (tumor-specific expansion study) dose and regimen using
a dose-escalation procedure.
6 to 18 subjects will participate in Part 1 and will receive a starting dose of
3 mg/kg and dose will deescalate or escalate between
(mg)/kilogram (kg) and 4.5 mg/kg. Up to 6 subjects will be enrolled at one dose
level dependent upon the number of subjects at the current dose level, the
number of subjects who have experienced a dose limiting toxicity (DLT) at the
current dose level, and the number of subjects enrolled but with data pending
at the current dose level. Escalation may proceed until either a maximum
tolerated dose (MTD) is established, or until the dose in which the median
pharmacokinetic parameters consistent with exposure in adults are achieved.
Cohorts may be added in order to evaluate additional dose levels.
consists of four disease-specific cohorts of subjects with tumors known to have
BRAF V600 activation (pediatric low -grade gliomas, pediatric high-grade
gliomas, Langerhans cell histiocytosis [LCH], and other tumors such as melanoma
and papillary thyroid carcinoma [PTC]). Each cohort will enroll at least 10
subjects with a pre-dose and at least 1 post-dose disease assessment.
In both the
parts of the study, on Day 1, a single first dose will be administered, and
repeat dosing will begin on Day 2. PK sampling will be performed on Day 1 and
Day 15 for subjects >=25 kg in weight. For subjects <25 kg in weight,
blood samples for PK analysis will be collected after repeated administration
on Day 15 only.
tolerability will be assessed throughout the study. Treatment with dabrafenib
will be continued until disease progression or until no clinical benefit or
development of an unacceptable toxicity, or until they withdraw consent or
begin a new therapy. At the end of treatment, a final study visit
Study Type: Interventional
Masking: Open Label
Primary Purpose: Treatment