Evaluation of the Irinotecan/Bevacizumab Association for Naive Unresectable Glioblastoma

Inclusion criteria

All the eligibility criteria must be met before registration :

• delay upper or equal to 14 days from stereotaxic biopsy and 28 days from surgical biopsy
• Histopathologically proven diagnosis of glioblastoma (WHO grade IV astrocytoma)
• Patient belonging to the RPA V class or associated
• only supratentorial glioblastoma
• Diagnosis must be obtained by a stereotactic or surgical biopsy
• Age between 18 and 70
• A contrast-enhanced MRI must be performed within 28 days prior to study registration
• Total or partial surgical resection deemed as not possible by a neurosurgeon
• Karnofsky Index (KI) performance status over 50
• Life expectancy of at least 3 months
• A stable dose of corticosteroid for at least 7 days to control intracranial pressure and neurological symptoms
• Adequate blood function : absolute neutrophil count > 1.5 x 109/L, platelets count > 100 x 109/L platelets; hemoglobin > 10 g/dl after blood transfusion if required
• Adequate liver function: bilirubin < 1.5 ULN (upper limit of normal), ALT and AST < 2.5 ULN, Prothrombin rate > 75 %
• Adequate renal function: creatinine < 1.2 ULN; proteinuria test 0 or trace (or urine protein concentration < 1g/24h if proteinuria test is + or ++).
• Negative pregnancy test for women of childbearing potential and adequate contraception for men and women.
• systolic arterial blood pressure at rest ≤ 170 mmHg
• Patient must have been informed and must have signed the specific informed consent form.
• holder of a coverage by the health insurance

Exclusion criteria

• patient belonging to the RPA III or IV
• prior malignant tumor in the recent 5 years or concomitant malignancy
• prior anti-tumoral chemotherapy or radiotherapy
• prior gross resection of the brain tumor
• patient receiving gliadel
• cardiovascular contra-indications to bevacizumab : prior angina pectoris, prior myocardial infarction, prior brain stroke, even transient, distal severe arteriopathy, uncontrolled high blood pressure
• anticomitial drug p450 cytochrome inductors
• other substances inducing p450 cytochrome
• proteinuria ≥ 1g/L
• concurrent anticoagulant or platelet anti-aggregant treatment
• congenital haemorrhagic pathology (haemophilia, Willebrandt)
• sign of brain haemorrhage on the RMI initial exam
• non resolved infectious disease
• non controlled arterial hypertension (≥170 mmHg)
• intracranial high pressure not controlled by a stable dose of steroids for at least 7 days
• pregnancy or refusal of the contraception for women and men
• psychiatric, behavioural disorders or geographical situation precluding the administration or follow-up of the protocol (including claustrophobia)
• digestive haemorrhage and / or gastro-duodenal ulcer occurring in the last 3 months
• pregnant, nursing woman, or without contraception
• private individuals of freedom or under tutelage (including legal guardianship)