Cetuximab, Bevacizumab and Irinotecan for Patients With Malignant Glioblastomas

Inclusion criteria

• Written informed consent
• Histological verification of primary GBM
• Recurrence or progression after standard treatment (debulking surgery of possible, radiotherapy and temozolamide within last six months)
• Evidence of measurable recurrent progressive primary GBM (CT/MRI scan)
• PS 0-2 (ECOG scale)
• Age > 18
• Life expectancy > 3 month
• Normal organ function:
• Platelets > 125 x 109/l
• Hemoglobin >6,2 mmol/l
• Leukocytes > 3 x 109/l
• ACN> 1,5 x 109/l
• ASAT and/or ALAT < 3 x upper normal limit
• Bilirubin < 1,5 x upper normal limit
• Creatinine clearance > 45 ml/min
• Creatinine < 1,5 x upper normal limit
• APTT < normal limit
• INR < normal limit
• Cholesterol < 7 mmol/l
• Fertile females must use oral contraceptive, IUD (intrauterine device) or preservatives. Fertile males must use preservatives.

Exclusion criteria

• Radiotherapy or chemotherapy within the last 4 weeks.
• Co-medication that may interfere with study results; e.g. immunosuppressive agents other than corticosteroids
• Prior EGFR- or VEGFR- based therapy.
• Any condition (medical, social, psychological), which would prevent adequate information and follow-up
• Any other active malignancy or previous malignancies within the last 5 years, except, adequately treated basal or squamous cell carcinoma of the skin, or carcinoma in situ.
• No hypercholesterolemia or hypertriglyceridemia (despite lipid-lowering therapy).
• Any significant cardiac disease (New York Heart Association Class II or greater), arrhythmia, congestive heart failure, acute myocardial infarction within 6 months or unstable angina pectoris.
• Clinically significant peripheral vascular disease
• Evidence of bleeding diathesis, coagulapathy or taking ASA, NSAIDs or clopidogrel
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 0, anticipation of need for major surgical procedure during the curse of the study
• Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to day 0
• History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 month prior to day 0
• History of known HIV, Hepatitis B and Hepatitis C negative
• Any ongoing infection, uncontrolled diabetes mellitus, serious non-healing wound, ulcer or bone fracture
• Pregnancy or breast feeding
• Requires therapeutic anti-coagulation
• Blood pressure > 150/100 mmHG
• Grade 2 or greater proteinuria