In:
Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 25, No. 24 ( 2019-12-15), p. 7294-7302
Abstract:
The 2-part, phase I/IIa, open-label study (NCT01677741) sought to determine the safety, tolerability, pharmacokinetics, and preliminary activity of dabrafenib in pediatric patients with advanced BRAF V600–mutated cancers. Patients and Methods: This phase I dose-finding part treated patients ages 1 to & lt;18 years with BRAF V600 mutation–positive tumors with oral dabrafenib 3 to 5.25 mg/kg/day to determine the RP2D based on safety and drug exposure target. Results: Between May 2013 and November 2014, 27 patients [12 male; median age, 9 years (range, 1–17 years)] with BRAF V600–mutant solid tumors recurrent/refractory to treatment (low- or high-grade glioma, Langerhans cell histiocytosis, neuroblastoma, or thyroid cancer) were enrolled. The median treatment duration was 75.6 weeks (range, 5.6–148.7 weeks), with 63% treated for & gt;52 weeks and 52% undergoing treatment at data cutoff date. The most common grade 3/4 adverse events suspected to be related to study drug were maculopapular rash and arthralgia (2 patients each). No dose-limiting toxicities were observed. Pharmacokinetic analyses showed a dose-dependent increase in AUC0–12 and achievement of adult exposure levels at the recommended phase II doses of 5.25 mg/kg/day (age & lt;12 years) and 4.5 mg/kg/day (age ≥12 years) divided into 2 equal doses daily, not exceeding 300 mg daily. Conclusions: In this first clinical trial in pediatric patients with pretreated BRAF V600–mutant tumors, dabrafenib was well tolerated while achieving target exposure levels; the average treatment duration was & gt;1 year with many patients still on treatment. The phase II component is also closed and will be reported separately.
Type of Medium:
Online Resource
ISSN:
1078-0432
,
1557-3265
DOI:
10.1158/1078-0432.CCR-17-3572
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2019
detail.hit.zdb_id:
1225457-5
detail.hit.zdb_id:
2036787-9
Permalink