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)]


Brain Tumor

Diseases Treated:

Brain tumors (recurrent and refractory)

Eligibility Overview:

  • 25 years or younger at time of registration
  • Histologically confirmed diagnosis of a primary central nervous system tumor
  • Positive test for the BRAFV600E or the BRAF Ins T mutation at a CLIA-approved laboratory


This study will enroll participants who have a brain tumor that is either growing or has come back (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 considered investigational.

The purpose of this study is to test the safety of the adult dose of Vemurafenib in children and young adults with brain tumors. Doctors want to find out the good and bad effects of the drug on brain tumors.

Primary Objectives

  • To determine if the maximum tolerated dose of Vemurafenib established in adults is safe and tolerable in pediatric patients with BRAFV600E or BRAF Ins T mutant brain tumors
  • To describe the toxicity profile and define the dose-limiting toxicity of Vemurafenib in children with recurrent or refractory BRAFV600E or BRAF Ins T mutant brain tumors
  • To characterize the pharmacokinetics of Vemurafenib in pediatric patients
  • To document anti-tumor activity of treatment with Vemurafenib, as measured by objective responses


Inclusion Criteria (among others):

  • 25 years old or younger
  • Histologically confirmed diagnosis of a primary central nervous system tumor.
  • Positive tumor test for the BRAFV600E mutation or the BRAF Ins T mutation at a CLIA-approved laboratory
  • Failed at least one prior therapy besides surgery:
    • Myelosuppressive chemotherapy: Received last dose at least three weeks prior to study registration or at least six weeks if nitrosurea
    • Biologic agent: Recovered from any toxicity and received last dose at least seven days prior to study registration
    • Monoclonal antibody treatment: At least three half-lives elapsed prior to registration
    • Radiation: Last fraction of local radiation to primary tumor or last fraction of craniospinal or total body irradiation at least 12 weeks prior to registration
    • Bone marrow transplant:
      • At least six months since allogeneic bone marrow transplant prior to registration
      • At least three  months since autologous bone marrow transplant prior to registration

Exclusion Criteria (among others):

  • Previous BRAF inhibitor use
  • Known diagnosis of Neurofibromatosis Type 1 or other known RAS-opathies
  • Currently receiving any other anticancer or investigational drug therapy
  • Unable to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy
  • History of allergic reaction attributable to compounds of similar chemical or biologic composition to Vemurafenib
  • Negative result of BRAFV600E and BRAF Ins T 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).


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


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

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.