Evaluation of the Irinotecan/Bevacizumab Association as Neo-adjuvant and Adjuvant Treatment of Chemoradiation With Temozolomide for Naive Unresectable Glioblastoma. Phase II Randomized Study With Comparison to Chemoradiation With Temozolomide
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)