Phase II Trial to Assess the Radiosensitizing Effect of ZARNESTRA in Patients With Glioblastoma Multiforme

Phase I/II Trial to Assess the Radiosensitizing Effect of ZARNESTRA in Patients With Glioblastoma Multiforme

The purpose of this study is to determine the efficacy by the determination of the Time To Progression (TTP) in patients with resectable GBM or non surgical GBM with a size less than 5 cm treated with the combination of ZARNESTRA plus Radiation therapy.

Inclusion Criteria:

• Patients must have pathologically confirmed (histology or cytology), resectable or non resectable, glioblastoma multiforme with a size < 5 cm on MRI if non resectable
• Patients must be at least 7 days but no more than 2 months since surgery or biopsy.
• Patients must have an ECOG Performance Status ≤ 2.
• Patients must be aged 18
• Patient has signed the informed consent form

Exclusion Criteria:

• Patients with unresectable glioblastoma with a size >5 cm on MRI
• Patients with clinically apparent leptomeningeal metastases
• Patients with uncontrolled seizures despite standard anticonvulsant therapy
• Any prior systemic treatment (chemotherapy, immunotherapy, hormonal therapy) for glioblastoma multiforme
• Significantly abnormal haematological status as judged by:

Absolute neutrophil count (ANC) < 1500/mm3 (1.5*109/l) Platelet count <100,000/mm3 (100*109/l)

• Serum bilirubin >2 mg/dl (>34 mmol/l) or Transaminase >2.5x the upper limit of institutional normal or Creatinine >1.5 mg/dl (>132 mmol/l)
• Inability to co-operate with the treatment protocol
• Patients who cannot undergo imaging evaluations
• Participation in an investigational drug trial in the 30 days prior to selection
• Pregnant or nursing mothers. (Female patients of childbearing potential must use adequate contraception.)
• Any malignancy within the past five years. Exceptions are: superficial basal cell carcinoma or non-metastatic squamous cell cancer of the skin, cervix cancer (cervical intra-epithelial neoplasia -CIN or FIGO stage 1) or prostate intra-epithelial neoplasia (PIN), biochemical relapse free for at least 3 years.
• Any prior systemic chemotherapy in the past five years for any malignancy in the medical history
• Any concurrent disease that in the opinion of the investigator would constitute a hazard for participating in this study
• Known sensitivity to imidazole derivatives
• Patients under law protection
• Medical history of phlebitis or pulmonary embolism, thrombocytosis, myocardiopathy, or other relevant cardiac pathology (auricular flutter, auricular fibrillation)
• Medical history of immuno-allergic pneumopathy