Clinical Trial Finder

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

Arms

Experimental: arm I

Bevacizumab + Irinotecan and concomitant radiotherapy

Experimental: Arm II

Bevacizumab and Temozolomide and concomitant radiotherapy

Interventions

Drug: - bevacizumab and Irinotecan and radiotherapy

- Bevacizumab 10 mg/kg is administered on days 1 and 15. - Irinotecan: - Irinotecan 125 mg/m2 is administered on days 1 and 15 to patients NOT receiving enzyme-inducing antiepileptic drugs (EIAED). - Irinotecan 340 mg/m2 is administered on days 1 and 15 to patients receiving EIAEDs. - During concomitant chemoradiotherapy, bevacizumab and irinotecan are given in the same doses and schedules as before and after chemoradiotherapy. Radiotherapy is delivered during 3rd and 4th cycle of chemotherapy and consists of fractionated focal irradiation at a dose of 2 Gy per fraction given once daily five days per week (Monday to Friday) over a period of six weeks for a total dose of 60 Gy.

Drug: - Bevacizumab and Temozolomide and radiotherapy

Bevacizumab 10 mg/kg is administered on days 1 and 15. Temozolomide dosing before start concomitant chemoradiotherapy: 150 mg/m2/day on days 1-5 during the first 28 days treatment cycle, then 200 mg/m2/day on the subsequent cycles until radiotherapy. Temozolomide administered concomitantly with the radiotherapy: Temozolomide 75 mg/m2/day for 7 days per week is administered on each day of radiotherapy. After completed chemoradiotherapy, temozolomide is dosed and administered as it was prior to start chemoradiotherapy, i.e. temozolomide 200 mg/m2/day on days 1-5 out of a 28 days schedule, taking into consideration any previous dose-reductions already made. Radiotherapy is delivered during 3rd and 4th cycle of chemotherapy and consists of fractionated focal irradiation at a dose of 2 Gy per fraction given once daily five days per week (Monday to Friday) over a period of six weeks for a total dose of 60 Gy.