• Progression free survival at 6 months [ Designated as safety issue: No ]
• Safety [ Designated as safety issue: Yes ]

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well bevacizumab works in treating patients with recurrent high-grade glioma.

OBJECTIVES:

Primary

• Determine the antitumor activity of bevacizumab, as determined by progression-free survival, in patients with recurrent high-grade glioma.
• Determine the safety of bevacizumab in these patients.

Secondary

• Estimate the objective radiographic response rate.
• Correlate objective radiographic response rates with progression-free survival.
• Evaluate the utility of serial MRI blood perfusion scans immediately prior to and after administration of bevacizumab as a tool to evaluate response.
• Correlate changes in serial PET scans with progression-free survival.
• Characterize pattern of changes in the number of endothelial progenitor cells over time and across patients.
• Determine the effects of response to treatment (stable disease or radiographic response) on quality of life of these patients.

OUTLINE: This is an open-label study. Patients are stratified according to tumor type (glioblastoma multiforme or gliosarcoma vs anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed oligoastrocytoma, or malignant astrocytoma [not otherwise specified]).

Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15. Courses repeat every 28 days for up to approximately 1 year in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at the baseline, prior to each course of study treatment, and then within 2 weeks after completion of study treatment.

After completion of study treatment, patients are followed within 2 weeks.

PROJECTED ACCRUAL: A total of 88 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically proven intracranial malignant glioma, including the following:

  • Glioblastoma multiforme
  • Gliosarcoma
  • Anaplastic astrocytoma
  • Anaplastic oligodendroglioma
  • Anaplastic mixed oligoastrocytoma
  • Malignant astrocytoma not otherwise specified
• Recurrent disease

• Patients must have evidence of tumor progression by MRI or CT scan (performed within the past 14 days and while on a fixed dose of steroids for at least 5 days)

  • Progressive disease after radiation therapy
• No evidence of acute intracranial/intratumoral hemorrhage

PATIENT CHARACTERISTICS:

• Life expectancy > 8 weeks
• Karnofsky performance status ≥ 60%
• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10 g/dL
• SGOT and bilirubin < 2 times upper limit of normal
• Creatinine < 1.5 mg/dL and/or creatinine clearance ≥ 60 mL/min
• No significant medical illnesses that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the patients' ability to tolerate this therapy
• No proteinuria by dipstick or urinalysis OR urine protein < 1,000 mg by 24-hour urine collection (for patients with proteinuria ≥ 1+ or urine protein:creatinine ratio > 1.0)
• Not pregnant or nursing
• Fertile patients must use effective contraception during and for ≥ 6 months after completion of study therapy
• No significant active cardiac, hepatic, renal, or psychiatric diseases
• No other malignancy that has required treatment in the past 12 months or will require treatment in the next 12 months, except for nonmelanoma skin cancer or carcinoma in situ of the cervix
• No active infections
• No disease that would obscure toxicity of the study drug
• No serious or nonhealing wound, ulcer, or bone fracture
• No significant traumatic injury within the past 28 days
• No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
• PT INR ≤1.5
• No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies

• No clinically significant cardiovascular disease, including any of the following:

  • Cerebrovascular accident within the past 6 months
  • Uncontrolled hypertension (> 150/100 mm Hg)
  • Myocardial infarction or unstable angina within the past 6 months
  • New York Heart Association class II-IV congestive heart failure
  • Serious cardiac arrhythmia requiring medication
  • Unstable angina pectoris
  • Clinically significant peripheral vascular disease
• No evidence of bleeding diathesis or coagulopathy

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Recent resection of recurrent or progressive tumor allowed provided patient has recovered from effects of surgery

  • Residual disease allowed, but not required
• No radiation therapy within the past 4 weeks
• Recovered from toxic effects of prior therapy
• At least 2 weeks since prior investigational agent
• At least 4 weeks since prior cytotoxic therapy
• At least 2 weeks since prior vincristine
• At least 6 weeks since prior nitrosoureas
• At least 3 weeks since prior procarbazine

• At least 1 week since prior noncytotoxic agents (e.g., interferon, tamoxifen, thalidomide, and tretinoin)

  • Does not include radiosensitizers
• No concurrent standard anticancer chemotherapy, investigational agents, radiotherapy, or immunotherapy
• No other concurrent anticoagulation or antiplatelet medication, including aspirin, nonsteroidal anti-inflammatories, or cyclooxygenase-2 inhibitors
• No major surgical procedure or open biopsy within the past 28 days
• No core biopsy within the past 7 days
• No major surgical procedures during the course of the study