Avastin in Combination With Radiation and Temozolomide, Followed by Avastin, Temozolomide and Irinotecan for Glioblastoma Multiformes and Gliosarcomas

Inclusion Criteria:

- Patients must have histologically confirmed diagnosis of World Health Organization
(WHO) grade IV primary malignant glioma (glioblastoma multiforme or gliosarcoma).
Patients have to be within 4 weeks of the last major surgical procedure.

- Age > 18 years.

- An interval of at least 2 weeks and not > 6 weeks between prior major surgical
procedure and study enrollment.

- No prior radiotherapy or chemotherapy for a brain tumor

- Karnofsky ≥ 60 percent.

- Hemoglobin ≥ 9.0 g/deciliter (dl), absolute neutrophil count (ANC) ≥ 1,500 cells/
microliter, platelets ≥ 125,000 cells/microliter.

- Serum creatinine ≤ 1.5 mg/dl, serum serum glutamic-oxaloacetic transaminase (SGOT)
and bilirubin ≤ 1.5 times upper limit of normal (ULN).

- For patients on corticosteroids, they must be on a stable or decreasing dose for 1
week prior to entry, and the dose should not be escalated over entry dose level, if
clinically possible.

- Signed informed consent approved by the Institutional Review Board

- No evidence of > grade 1 central nervous system (CNS) hemorrhage on the baseline MRI
or CT scan.

- If sexually active, patients will take contraceptive measures for the duration of
treatment as stated in the informed consent.

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 intravenous (IV) antibiotics.

- Prior 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 on CT scan.

Avastin-Specific Concerns:

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

- Blood pressure of 150/100 mmHg

- Unstable angina

- New York Heart Association (NYHA) Grade II or greater congestive heart failure

- History of myocardial infarction within 6 months

- History of stroke within 6 months

- Clinically significant peripheral vascular disease

- Evidence of bleeding diathesis

- Coagulopathy (prothrombin time (PT) or partial thromboplastin time (PTT) >1.5x normal
or a history of > three grade 2 or greater hemorrhages)

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to first Avastin infusion during XRT/Temodar or anticipation of need for major
surgical procedure during the course of the study

- Minor surgical procedures, fine needle aspirations or core biopsies within 7 days
prior to first Avastin infusion during XRT/Temodar

- Pregnant (positive pregnancy test) or lactating

- Urine protein >1.0 + at screening

- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to first Avastin infusion during XRT/Temodar

- Serious, non-healing wound, ulcer, or bone fractures.

- Inability to comply with study and/or follow-up procedures.