Dabrafinib in Children with advanced BRAF V600 - Mutation Positive Solid Tumors

Author: Julia Dobke, erstellt am: 2016/12/21, Last modification: 2018/09/12

Dabrafinib in Children with advanced BRAF V600 - Mutation Positive Solid Tumors Phase I/IIa, 2-Part, Multi-Center, Single-Arm, Open-Label Study to Determine the Safety, Tolerability and Pharmacokinetics of Oral Dabrafenib in Children and Adolescent Subjects with Advanced BRAF V600-Mutation Positive Solid Tumors.Dabrafinib in Children with advanced BRAF V600 - Mutation Positive Solid Tumors
Disease Children and adolescent subjects with advanced BRAF V600-Mutation positive solid Tumors
Type A 2-part (part 1 dose escalation, part 2 tumor-specific expansion), Phase I/IIa, multi-center, open label, study
Problem / Objectives

Primary objectives

To determine the safe and tolerable dabrafenib dose(s) for chronic dosing in pediatric subjects (infants, children, and adolescents) that achieves similar exposures to the dabrafenib adult dose, in subjects with BRAF V600 mutation positive tumors.

Secondary objectives

  • To characterize the pharmacokinetics of dabrafenib, and its metabolites
  • To characterize the longer term safety and tolerability of dabrafenib
  • To assess any preliminary anti-tumor activity of dabrafenib
  • To determine the effect of age and weight on the pharmacokinetics of dabrafenib using a population pharmacokinetics approach
Inclusion Criteria
  • Male or female ≥12 months and <18 years of age at the time of signing the informed consent form.
  • Recurrent disease, refractory disease, or progressive disease after having received at least one standard therapy for their disease;
  • At least one evaluable lesion.
  • BRAF V600 mutation-positive tumor as confirmed in a CLIA-approved lab or equivalent. Please NOTE: Local BRAF testing may be subject to subsequent verification by centralized testing; centralized testing can confirm V600 E and V600K mutations only.
  • Performance score of >50% according to the Karnofsky/Lansky performance status scale
  • Must have adequate bone marrow, renal, liver and cardiac organ function as defined by the following values.
Exclusion Criteria
  • Part 2 ONLY: Previous treatment with dabrafenib, another RAF inhibitor, or a MEK inhibitor (exception: prior treatment with sorafenib is permitted)
  • Malignancy OTHER than the BRAF mutant malignancy under study
  • Had chemotherapy or radiotherapy within 3 weeks (or 6 weeks for nitrosoureas or mitomycin C) prior to administration of the first dose of study treatment
  • The subject has received an investigational product within the following time period prior to the first dosing day in the current study: 28 days or 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is warranted by the data)
  • History of another malignancy.
  • Unresolved toxicity greater than NCI CTCAE v4.0 [NCI, 2009] Grade 2 or higher from previous anti-cancer therapy, including major surgery, except those that in the opinion of the investigator are not clinically relevant given the known safety/toxicity profile of dabrafenib (e.g., alopecia and/or peripheral neuropathy related to platinum or vinca alkaloid based chemotherapy)
  • Has leukaemia
  • Autologous or allogeneic stem cell transplant within 3 months prior to enrolment [NOTE: subjects with evidence of active graft versus host disease are excluded]
EudraCT 2012-001499-12
Entry Study Register
Principal Investigator Prof. Dr. med. Olaf Witt, Dr. Cornelis van Tilburg
URL http://pediatric-neurooncology.dkfz.de/index.php/de/therapie/zipo
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Participants Heidelberg, Berlin, Regensburg
Sponsoring GlaxoSmithKline plc