BRF116: A Study to Determine Safety, Tolerability and Pharmacokinetics of Oral Dabrafenib In Children and Adolescent Subjects

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 Advance BRAF V600-Mutation Positive Solid Tumors

Categories:

Brain Tumor

Solid Tumor

Phase I/II

Diseases Treated:

Solid tumors, giomas, hystiocytosis

Eligibility Overview:

  • Participant is greater or equal to 12 months and less than 18 years at the time of signing the informed consent form.
  • Participant has BRAF V600 mutation positive tumor as confirmed in a CLIA-approved laboratory or equivalent
  • Participant has recurrent disease, refractory disease, or progressive disease after having received at least one standard therapy for their disease, OR participant has metastatic (or surgically unresectable) melanoma, and is being enrolled for first-line treatment. Melanoma participants with CNS involvement may be enrolled.

Description

The purpose of the study is to test the safety of dabrafenib given at different doses and find out what effects; good or bad, dabrafenib has on children one year to 17 years old who have certain kinds of cancerous tumors (BRAF V600 mutation positive tumors), as well as to find out how much of the drug gets into the blood stream and how long the body takes to get rid of it.

The study has two parts. Each participant will take part in only one part of the study. In Part 1, dabrafenib will be given at different doses to see which dose is safest to give to children. In Part 2, the dose will be set depending on the results of Part 1. In Part 2, dabrafenib will be further tested for how safe, how well tolerated and how active it is.

Dabrafenib has been approved by the Food and Drug Administration (FDA) for doctors to prescribe to adult patients with metastatic melanoma. So far, over 1,000 adults and five children less than 18 years of age have received dabrafenib in other studies. Dabrafenib has not been approved by the FDA for use in children; therefore, the use of dabrafenib in this study is experimental.

Objectives (Primary and Secondary)

  • To determine the safe and tolerable Dabrafenib dose(s) for chronic dosing in pediatrics (infants, children, and adolescents) that achieves similar exposures to the Dabrafenib adult dose, in subjects with BRAF V600 mutation positive tumors. (Primary)
  • To characterize the pharmacokinetics of Dabrafenib, and its metabolites.
  • To assess any preliminary anti-tumor activity in Dabrafenib.
  • To characterize the long term safety and tolerability of Dabrafenib.
  • To determine the effect of age and weight on the pharmacokinetics of Dabrafenib using a population pharmacokinetics approach.

Eligibility criteria, among others, include:

  • Participant is greater or equal to 12 months and less than 18 years at the time of signing the informed consent form.
  • Participant has BRAF V600 mutation positive tumor as confirmed in a CLIA-approved laboratory or equivalent
  • Participant has recurrent disease, refractory disease, or progressive disease after having received at least one standard therapy for their disease, OR participant has metastatic (or surgically unresectable) melanoma, and is being enrolled for first-line treatment. Melanoma participants with CNS involvement may be enrolled.
  • Participant has at least one evaluable lesion.
  • Participant has a performance score = or >50 according to the Karnofsky/Lansky performance scores
  • Participant does NOT have Leukemia
  • Participant has NOT had chemotherapy or radiotherapy within 3 weeks ( or 6 weeks for nitrosureas or mitomycin C) prior to administration of the first dose of the study drug
  • Participant does not have a malignancy OTHER than the BRAF mutant malignancy under study

Contact

Alberto Broniscer, MD

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Phone: 901-595-2544 or 901-595-4599
Fax: 901-595-6211

OR

Tabatha E. Doyle, RN
Coordinator, Brain Tumor Program
MS 260
262 Danny Thomas Place
Memphis, TN 38105
Phone: (901) 595-2544
FAX: (901) 595-6211

Referring or consulting clinicians only: protocolinfo@stjude.org
For all other inquiries about St. Jude Children's Research Hospital studies: referralinfo@stjude.org

The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.