PNOC002: A Safety Phase 0, and Pilot Efficacy Study of Vemurafenib, an oral inhibitor of BRAFV600E in Children with Recurrent/Refractory BRAFV600E-Mutant Brain Tumors [PNOC-002, CC #120819, IND#116870 (exempt)]

Category:

Brain Tumor

Diseases Treated:

Brain tumors (recurrent and refractory)

Eligibility Overview:

  • Participant enrolling on the MTD cohort is less than eight-teen (18) years of age at registration or if enrolling on the expansion cohort is less than or equal to twenty-five (25) years of age at time of registration.
  • Participant has histologically confirmed diagnosis of glioma (WHO Grades I-IV).
  • Participant tumor has tested positive for the BRAFV600E mutation at a CLIA approved laboratory.

Description

This study will enroll participants who have a brain tumor that is either growing or has comeback (recurred) after receiving standard therapy. People not on a study are usually treated with additional surgeries, radiation, and/or chemotherapy using drugs that are considered standard of care. In this study the drug Vemurafenib is used. This drug is approved by the FDA as a treatment for skin cancer. However this drug has not been approved to treat brain tumors and is therefore considered investigational. The purpose of this study is to test the safety of the adult dose of Vemurafenib in pediatric patients with brain tumors. The doctor(s) want to find out what effects either good or bad the drug has on brain tumors. This study has two parts, the pre-screen which will be used to determine eligibility for the actual treatment phase of the study. In the pre-screen a tissue sample will be taken to determine if the participant meets diagnostic criteria for participation in the treatment phase of the study. The treatment phase has two groups or cohorts. Participants will be enrolled in the maximum tolerated dose (MTD) group or the expansion group.

Objectives

  • To determine if the maximum tolerated dose of Vemurafenib established in adults is safe and tolerable in pediatric patients with BRAFV600E mutant gliomas (dose is adjusted for pediatric use. Weighted dose extrapolated from FDA approved standard adult dose).
  • To describe the toxicity profile and define the dose limiting toxicity of Vemurafenib in children with recurrent or refractory BRAFV600E mutant gliomas.
  • To characterize the pharmacokinetics of Vemurafenib in pediatric patients.
  • To document anti-tumor activity of treatment with Vemurafenib, as measured by objective responses.

Eligibility

Inclusion Criteria (among others):

  • Participant enrolling on the MTD cohort is less than eight-teen (18) years of age at registration or if enrolling on the expansion cohort is less than or equal to twenty-five (25) years of age at time of registration.
  • Participant has histologically confirmed diagnosis of glioma (WHO Grades I-IV).
  • Participant tumor has tested positive for the BRAFV600E mutation at a CLIA approved laboratory.
  • Participant has failed at least one prior therapy besides surgery- radiation or chemotherapy (either cytotoxic or biologic agent prior to registration).
  • Participant received his or her last dose of myelosuppressive anti-cancer chemotherapy at least three (3) weeks prior to study registration or at least six weeks (6) if nitrosurea.
  • Participant had his/her last fraction of local radiation to primary tumor or last fraction of cransiospinal or total body irradiation greater than or equal to twelve (12) weeks prior to registration.
  • Participant is greater than or equal to six (6) months since allogeneic bone marrow transplant or three (3) months since autologous bone marrow transplant prior to registration.

Exclusion:

  • Participant is unable to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.
  • Participant has history of allergic reaction attributable to compounds of similar chemical or biologic composition to Vemurafenib.
  • Participant has negative result of BRAFV600E pre-screening test.

For the current eligibility status of this clinical study, referring physicians must contact St. Jude Children's Research Hospital at 1-866-2ST-JUDE (1-866-278-5833).

Contact

Ibrahim Qaddoumi, 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.