Bevacizumab and Temozolomide Following Radiation and Chemotherapy for Newly Diagnosed Glioblastoma Multiforme

Inclusion Criteria

• Disease-Specific Concerns Histologically confirmed GBM as determined by central pathology review Supratentorial location
• General Medical Concerns 18 years of age; Karnofsky performance status > 60; Tumor-related contrast enhancement on initial and post-operative Gd-MRI; Recovery from effects of surgery and/or its complications prior to initiating radiotherapy; Radiotherapy must begin 10 grams hematocrit > 30%, platelets > 100,000 per mm3, BUN 100 mmHg on antihypertensive medications); Any prior history of hypertensive crisis or hypertensive encephalopathy; History of myocardial infarction or unstable angina within 6 months prior to study enrollment; History of stroke or transient ischemic attack within 6 months prior to study enrollment; New York Heart Association (NYHA) Grade II or greater CHF (see Appendix E); Significant vascular disease (e.g., aortic aneurysm, aortic dissection); Symptomatic peripheral vascular disease; Evidence of bleeding diathesis or coagulopathy; History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment; History of intracerebral abscess within 6 months prior to study enrollment; Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment (exclusive of craniotomy); anticipation of need for major surgical procedure during the course of the study; Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment; Serious non-healing wound, ulcer, or bone fracture; Proteinuria at screening as demonstrated by either; Urine protein:creatinine (UPC) ratio 1.0 at screening OR Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible); Known hypersensitivity to any component of Avastin. c. General Medical Exclusions

Subjects meeting any of the following criteria are ineligible for study entry:

Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored Avastin cancer study; History of any other malignancy within 5 years (except non-melanoma skin cancer or carcinoma in situ of the cervix);Pregnant or nursing females; Unstable systemic disease, including active infection, uncontrolled hypertension, or serious cardiac arrhythmias requiring medication;

Screening clinical laboratory values:

Absolute neutrophil count 1.6 mg.dl, AST/ALT > 1.5 x the upper limit of normal ( ULN), Creatinine > 1.2 x ULN, Urine protein/creatinine ratio > 1.0, International normalized ration (INR) > 1.5 and activated partial thromboplastin time (aPTT) > 1.5 x ULN (except for subjects receiving anticoagulation therapy) in the absence of therapeutic intent to anticoagulate the subject. Therapeutic anticoagulation is permitted.