Bevacizumab and Irinotecan or Bevacizumab and Temozolomide With Concomitant Radiotherapy for Primary Glioblastoma Multiforme (GBM)

• 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