Treatment of primary glioblastoma multiforme with cetuximab, radiotherapy and temozolomide (GERT) – phase I/II trial: study protocol

BACKGROUND: The implementation of combined radiochemotherapy (RCHT) with temozolomide (TMZ) has lead to a significant increase in overall survival times in patients with Glioblastoma multiforme (GBM), however, outcome still remains unsatisfactory. The majority of GBMs show an overexpression and/or amplification of the epidermal growth factor receptor (EGFR). Therefore, addition of EGFR-inhibition with cetuximab to the current standard treatment approach with radiotherapy and TMZ seems promising. METHODS/DESIGN: GERT is a one-armed single-center phase I/II trial. In a first step, dose-escalation of TMZ from 50 mg/m(2 )to 75 mg/m(2 )together with radiotherapy and cetuximab will be performed. Should safety be proven, the phase II trial will be initiated with the standard dose of 75 mg/m(2 )of TMZ. Cetuximab will be applied in the standard application dose of 400 mg/m(2 )in week 1, thereafter at a dose of 250 mg/m(2 )weekly. A total of 46 patients will be included into this phase I/II trial. Primary endpoints are feasibility and toxicity, secondary endpoints are overall and progression-free survival. An interim analysis will be performed after inclusion of 15 patients into the main study. Patients' enrolment will be performed over a period of 2 years. The observation time will end 2 years after inclusion of the last patient. DISCUSSION: The goal of this study is to evaluate the safety and efficacy of combined RCHT-immunotherapy with TMZ and cetuximab as first-line treatment for patients with primary GBM.