Phase I study of vemurafenib in children with recurrent or progressive BRAFV600E mutant brain tumors: Pacific Pediatric Neuro-Oncology Consortium study (PNOC-002)
Theodore Nicolaides, Kellie J. Nazemi, John R. Crawford, Lindsay Kilburn, Jane E. Minturn, Amar Gajjar, Karen Gauvain, Sarah Leary, Girish Dhall, Mariam Aboian, Giles Robinson, Janel Long‐Boyle, Hechuan Wang, Annette M. Molinaro, Sabine Mueller, Michael D. Prados
Abstract
Background: BRAF V600E mutation is present in a subset of pediatric brain tumors. Vemurafenib is an oral, selective ATP-competitive inhibitor of BRAF V600E kinase. The goal of this multi-center study conducted through the Pacific Pediatric Neuro-Oncology Consortium (PNOC) was to determine the recommended phase 2 dose (RP2D) and dose limiting toxicities (DLTs) in children < 18 years with recurrent or progressive BRAF V600E mutant brain tumors. Results: Nineteen eligible patients were enrolled. Eleven patients had received three or more prior therapies. Data reported are from the start of treatment for the first patient (April 30 2014) through August 31 2019. The RP2D was defined as 550 mg/m 2 twice daily after DLT criteria adjustment for rash. Related grade 3 adverse events included secondary keratoacanthoma (n = 1); rash (n =16); and fever (n = 5). Subjects received a median of 23 cycles (range 3-63). Four patients remain www.oncotarget.com