Bevacizumab and Carmustine in Treating Patients With Relapsed or Progressive High-Grade Glioma

OBJECTIVES:

Primary

- To determine the 6-month progression-free survival of patients with relapsed or
progressive high-grade gliomas treated with bevacizumab and carmustine.

Secondary

- To evaluate the radiographic response to this regimen as measured by MRI and PET scan
with image fusion.

- To utilize novel brain imaging to differentiate between a radiographic response due to
tumor shrinkage and a radiographic response due to decreased vasogenic edema.

- To evaluate the safety and toxicity of this regimen in these patients.

- To evaluate the overall survival of these patients.

OUTLINE: Patients receive bevacizumab IV on days -7, 8, 22, 36, and 50 of course 1 and on
days 8, 22, 36, and 50 of all subsequent courses. Patients also receive carmustine IV over 4
hours on day 1. Treatment repeats every 56 days for up to 6 courses in the absence of
disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed every 3 months.

Inclusion Criteria:

- Histologically confirmed GBM, anaplastic astrocytoma, anaplastic oligoastrocytoma or
anaplastic oligodendroglioma.

- Disease progression (confirmed by MRI, PET or both) after radiation therapy

- At least 28 days have elapsed since chemotherapy, major surgery or radiation therapy.

- No other malignancy within 3 years except for non-melanomatous skin cancer or in situ
cervical cancer.

- Karnofsky performance score at least 70

- Platelet count ≥ 130/mm3.

- Absolute neutrophil count ≥ 1500/mm3

- Calculated creatinine clearance greater than 45 mg/dl

- AST < 2 times the upper limit of normal

- Bilirubin < 1.5 times the upper limit of normal

- Ability to give signed informed consent

- Patients must be 18 years of age or older.

Exclusion Criteria:

- Prior intravenous or oral nitrosoureas (BCNU, CCNU) or prior VEGF targeted therapy
including bevacizumab. No more than two prior chemotherapy regimens are allowed.
Prior or current steroid use is allowed.

- Evidence of CNS hemorrhage

- Requirement for therapeutic anticoagulation

- Any grade 3 or greater hemorrhage within the previous 28 days

- Active inflammatory bowel disease

- Inadequately controlled hypertension

- Any prior history of hypertensive crisis or hypertensive encephalopathy

- New York Heart Association 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

- 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

- Pregnant (or lactating). Use of effective means of contraception in subjects of
child-bearing potential

- Prior organ transplantation

- Known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human antibodies

- Known acquired immune deficiency syndrome (AIDS) or HIV positive status