Avastin/Radiation (XRT)/Temozolomide (Temodar) Followed by Avastin/Temodar/Topotecan for Glioblastoma

Inclusion Criteria:

• Patients must have histologically confirmed diagnosis of WHO grade IV primarymalignant glioma (glioblastoma multiforme or gliosarcoma). Patients have to be within 6 weeks of the last major surgical procedure.
• Age > or = to 18 years.
• An interval of at least 2 weeks and not > 6 weeks between prior major surgicalprocedure and study enrollment.
• No prior radiotherapy or chemotherapy for a brain tumor
• Karnofsky > or = to 60%.
• Hemoglobin ≥ 9.0 g/dl, absolute neutrophil count (ANC) ≥ 1,500 cells/microliter,platelets ≥ 125,000 cells/microliter.
• Serum creatinine ≤ 1.5 mg/dl, serum glutamic oxaloacetic transaminase (SGOT) andbilirubin ≤ 1.5 times upper limit of normal.
• Signed informed consent approved by the Institutional Review Board
• If sexually active, patients must agree to use appropriate contraceptive measures forthe duration of the study and for 6 months afterwards as stated in the informedconsent.

Exclusion Criteria:

• Pregnancy or breast feeding.
• Co-medication that may interfere with study results; e.g. immuno-suppressive agentsother than corticosteroids.
• Active infection requiring IV antibiotics.
• Prior treatment with radiotherapy or chemotherapy for a brain tumor, irrespective ofthe grade of the tumor.
• Evidence of > grade 1 central nervous system (CNS) hemorrhage on baseline MRI on CTscan. Avastin-specific Exclusion Criteria:
• Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/ordiastolic blood pressure > 100 mmHg)
• Prior history of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association (NYHA) Grade II or greater congestive heart failure
• History of myocardial infarction or unstable angina within 6 months prior to studyenrollment
• History of stroke or transient ischemic attack within 6 months prior to studyenrollment
• Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair orrecent peripheral arterial thrombosis) within 6 months prior to study enrollment
• History of hemoptysis (≥ ½ teaspoon of bright red blood per episode) within 1 monthprior to study enrollment
• Evidence of bleeding diathesis or coagulopathy (in the absence of therapeuticanticoagulation)
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 daysprior to study enrollment or anticipation of need for major surgical procedure duringthe course of the study
• Core biopsy or other minor surgical procedure, excluding placement of a vascularaccess device, within 7 days prior to study enrollment
• History of abdominal fistula, gastrointestinal perforation within 6 months prior tostudy enrollment
• Serious, non-healing wound, active ulcer, or untreated 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 discoveredto have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hoururine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).
• Known hypersensitivity to any component of Avastin
• Pregnant (positive pregnancy test) or lactation. Use of effective means ofcontraception (men and women) in subjects of child-bearing potential