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