Inclusion Criteria

Inclusion criteria:

- Signed informed consent

- Histological verified primary glioblastoma multiforme

- No prior therapy for GBM, except for primary surgical resection or biopsy

- PS 0-2

- Age > 18

- Expected survival > 3 months

- Adequate liver, renal and bone-marrow function, determined as:

- Thrombocytes > 100 x 109/liter

- Hemoglobin >6.2 mmol/liter

- Leukocytes > 3 x 109/liter

- Neutrophil granulocytes > 1.5 x 109/liter

- ASAT and/or ALAT < 3 x upper normal limit

- Bilirubin < 1.5 x upper normal limit

- Serum-creatinin < upper normal limit or glomerular filtration rate >60 ml/min
(corrected for age) determined by measurement of clearance of Cr-EDTA

- APTT < upper normal limit

- INR < upper normal limit

- Fertile women of childbearing age must use proper anti-conception (oral
contraceptives, IUD and/or condom). Fertile men must use condom

- No sign of cerebral bleeding on cerebral MR-scanning at baseline.

Exclusion criteria:

- Previous therapy of GBM, including radiotherapy and the use of biological " targeted"
drug, e.g. drugs targeted against the VEGF- or EGFR pathway

- Concurrent use of medication that can affect the interpretation of the results from
the study, e.g. use of immunosuppressive drugs, except corticosteroids

- Conditions (medical, social or physical) that may compromise proper information
and/or follow-up

- Other concurrent or previous cancer within 5 years, except adequately treated basal
or planocellular skin cancer, or cervical carcinoma in situ

- Significant heart disease (according to the New York Heart Association class II or
more severe), clinically significant arrhythmia or unstable angina pectoris/acute
myocardial infarction within last 6 months

- Clinical significant peripheral arterial disease

- Known or suspected disorders of coagulation or concurrent therapy with ASA, NSAID or
clopidogrel

- Major surgery, open biopsy or greater trauma, or expectations thereof, within 28 days
prior to start of therapy

- Minor surgery or needle biopsy, or expectations thereof, within 7 days prior to start
of therapy

- Known or suspected abdominal fistulas, gastrointestinal perforations or
intra-abdominal abscesses within 6 months prior to start of therapy

- Chronic inflammatory intestinal disease and/or intestinal obstruction

- Known or active HIV or Hepatitis B/C infection

- Concurrent ongoing significant infection or diabetes mellitus not adequately
controlled medically

- Clinically significant non-healing ulcers

- Active ventricular or duodenal ulcers within 6 months prior to start of therapy

- Recent bone-fracture (<3 months)

- Pregnancy or lactation

- Need for systemic anticoagulant therapy at time of start of therapy

- Blood pressure > 150/100 mmHg (patients are allowed to receive proper
antihypertensive medication)

- Proteinuria ≥ 1 gram/day

- Known allergy toward irinotecan (or related substance) or vehicle

- Known allergy toward temozolomide (or related substance) or vehicle

- Known allergy toward bevacizumab (or related substance) or vehicle