Avastin/Temozolomide/Irinotecan for Unresectable/Multifocal Glioblastoma Multiforme

Inclusion Criteria: * Patients must have histologically confirmed diagnosis of WHO grade IV primary malignant glioma (glioblastoma multiforme or gliosarcoma). Patients will be unresectable or have multifocal disease. * Age \> or = to 18 years and a life expectancy of \>12 weeks. * Evidence of measurable primary Central Nervous System (CNS) neoplasm on contrast enhanced MRI. * An interval of at least one week between prior biopsy or four weeks from surgical resection and enrollment on this protocol. * Karnofsky \> or = to 60%. * Hemoglobin \> or = to 9g/dl, absolute neutrophil count (ANC) \> or = to 1,500 cells/microliter, platelets \> or = to 125,000 cells/microliter. * Serum creatinine ≤ 1.5 mg/dl, serum serum glutamic oxaloacetic transaminase (SGOT) and direct bilirubin ≤ 1.5 times upper limit of normal (if the total bilirubin is greater than or equal to 1.5 x the upper limit of normal, then the direct bilirubin must be ≤ 1.5 x the upper limit of normal). * Signed informed consent approved by the Institutional Review Board prior to patient entry. * If sexually active, patients will take contraceptive measures for the duration of the treatments. Exclusion Criteria: * Pregnancy or breast feeding * Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids. * Active infection requiring IV antibiotics. * Treatment with radiotherapy or chemotherapy for a brain tumor, irrespective of the grade of the tumor. * Evidence of \> grade 1 CNS hemorrhage on baseline MRI or CT scan. Avastin-specific Exclusion Criteria: * Inadequately controlled hypertension (defined as systolic blood pressure \> 150 and/or diastolic blood pressure \> 100 mmHg on antihypertensive medications) * Any 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 study enrollment * History of stroke or transient ischemic attack within 6 months prior to study enrollment * Significant vascular disease (e.g., aortic aneurysm, aortic dissection) * Symptomatic peripheral vascular disease * Evidence of bleeding diathesis or coagulopathy * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or 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 * History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment * Serious, non-healing wound, ulcer, or bone fracture * Proteinuria at screening as demonstrated by either urine protein:creatinine (UPC) ratio \> or = to 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 * Pregnant (positive pregnancy test) or lactating. Use of effective means of contraception (men and women) in subjects of child-bearing potential