Pilot Efficacy Study of vemurafenib, an oral inhibitor of BRAFV600E, in Children with Recurrent/Refractory BRAFV600E-mutant gliomas


Trial Requirements and Treatment

Please note, this study has closed to accrual and is no longer accepting patients. || Patients will receive vemurafenib once daily by mouth. One course is 28 days. Subsequent courses will immediately follow, with no break in the administration of the drug. Clinical assessment will be required every 2 months for the first 6 months, then every 3 months for the next 6 months.

Rationale for Study

This trial is testing the drug vemurafenib (also called PLX4032) in children with pediatric astrocytomas that have the BRAFV600E mutation. Vemurafenib works by blocking the activity of BRAF, a key protein in the RAS/RAF/MAPK pathway that is overactive in these tumors. In normal cells, the molecules in this pathway deliver signals to one another that regulate important processes such as cell proliferation, natural cell death (also called apoptosis) and cell growth. A significant fraction of pediatric astrocytomas contain the BRAFV600E mutation, and this mutation is thought to be vital to tumor maintenance.

Subsequently, the study will attempt to document vemurafenib drug levels within surgically resected tumor samples. If drug levels are found to be meet our goals, an expanded cohort will be opened to measure efficacy of this drug in children with recurrent tumors.

Primary Objectives

The primary objectives of this study are:

  1. To characterize the pharmacokinetics of vemurafenib in pediatric patients
  2. During the pilot efficacy study, to document antitumor activity of treatment with vemurafenib, as measured by objective responses.

Secondary Objectives

  1. To document intra-tumoral drug concentration in patients treated with vemurafenib and compare them to serum drug levels pre-surgery
  2. To describe progression-free survival of patients treated on vemurafenib


Funding is provided by Genentech.