EORTC 26083 phase I/II trial of dasatinib in combination with CCNU in patients with recurrent glioblastoma

Enrico Franceschi, Roger Stupp, Martin J. Van Den Bent, Carla Van Herpen, Florence Laigle Donadey, Thierry Gorlia, Monika Hegi, Benoit Lhermitte, Lewis C. Strauss, Anouk Allgeier, Denis Lacombe, Alba A. Brandes*

*Corresponding author for this work

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

The treatment of patients with recurrent glioblastoma remains a major oncologic problem, with median survival after progression of 7-9 months. To determine the maximum tolerated dose and dose-limiting toxicity (DLT), the combination of dasatinib and cyclonexyl-chloroethyl-nitrosourea (CCNU) was investigated in this setting. The study was designed as multicenter, randomized phase II trial, preceded by a lead-in safety phase. The safety component reported here, which also investigated pharmacokinetics and preliminary clinical activity, required expansion and is therefore considered a phase I part to establish a recommended dosing regimen of the combination of CCNU (90-110 mg/m2) and dasatinib (100-200 mg daily). Overall, 28 patients were screened, and 26 patients were enrolled. Five dose levels were explored. DLTs, mainly myelosuppression, occurred in 10 patients. Grade 3 or 4 neutropenia was recorded in 7 patients (26.9) and thrombocytopenia in 11 patients (42.3). No significant effect of CCNU coadministration on dasatinib pharmacokinetics was found. Median progression-free survival (PFS) was 1.35 months (95 confidence interval: 1.2-1.4) and 6-month PFS was 7.7. In this phase I study of recurrent glioblastoma patients, the combination of CCNU and dasatinib showed significant hematological toxicities and led to suboptimal exposure to both agents.

Original languageEnglish (US)
Pages (from-to)1503-1510
Number of pages8
JournalNeuro-oncology
Volume14
Issue number12
DOIs
StatePublished - Dec 2012

Keywords

  • CCNU
  • dasatinib
  • recurrent glioblastoma

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

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    Franceschi, E., Stupp, R., Van Den Bent, M. J., Van Herpen, C., Laigle Donadey, F., Gorlia, T., Hegi, M., Lhermitte, B., Strauss, L. C., Allgeier, A., Lacombe, D., & Brandes, A. A. (2012). EORTC 26083 phase I/II trial of dasatinib in combination with CCNU in patients with recurrent glioblastoma. Neuro-oncology, 14(12), 1503-1510. https://doi.org/10.1093/neuonc/nos256