A phase II study of the farnesyl transferase inhibitor, tipifarnib, in children with recurrent or progressive high‐grade glioma, medulloblastoma/primitive neuroectodermal tumor, or brainstem glioma: A children's oncology group study

BACKGROUND. An open‐label Phase II study of tipifarnib was conducted to evaluate its safety and efficacy in children with recurrent or refractory medulloblastoma (MB)/primitive neuroectodermal tumor (PNET), high‐grade glioma (HGG), and diffuse intrinsic brainstem glioma (BSG). METHODS. Between January 2004 and July 2005, patients were enrolled and stratified as follows: Stratum 1, recurrent or refractory MB/PNET; Stratum 2, recurrent or refractory HGG; and Stratum 3, recurrent or refractory BSG. Patients received tipifarnib 200 mg/m 2 per dose twice daily for 21 days repeated every 28 days. Patients who received enzyme‐inducing anticonvulsants and other CYP3A4/5 inducers or inhibitors were excluded. The primary objective was to estimate the sustained response rate in all strata. RESULTS. Ninety‐seven patients with a median age of 11.2 years (range, 3.2–21.9 years) were enrolled on the study, and 81 patients were evaluable for response. One of 35 patients with BSG and 1 of 31 patients with HGG had a sustained partial response. No responses were observed in 15 patients with MB/PNET. Eight patients (3 HGG, 1 MB, and 4 BSG) remained stable for ≥4 courses (range, 4–25 courses). The median number of courses received was 2 (range, 1–25 courses). The most frequent grade 3 and 4 toxicities included neutropenia (18.7%), thrombocytopenia (14.3%), and leukopenia (14.3%). The 6‐month progression‐free survival rate (±standard deviation) was 14% ± 6% for HGG, 6% ± 6% for MB/PNET and 3% ± 3% for BSG. CONCLUSIONS. Tipifarnib tolerated well but had little activity as a single agent in children with recurrent central nervous system malignancies. Cancer 2007. © 2007 American Cancer Society.