Bevacizumab for Recurrent Malignant Glioma

* INCLUSION CRITERIA:
* Patients with histologically proven intracranial malignant glioma will be eligible for this protocol.
* Malignant glioma include glioblastoma multiforme (GBM),
* gliosarcoma,
* anaplastic astrocytoma (AA),
* anaplastic oligodendroglioma (AO),
* anaplastic mixed oligoastrocytoma (AMO),
* or malignant astrocytoma NOS (not otherwise specified).
* Patients must have evidence for tumor progression by magnetic resonance imaging (MRI) or computed tomography (CT) scan.
* This scan should be performed within 14 days prior to registration and on a fixed dose of steroids for at least 5 days.
* If the steroid dose is increased between the date of imaging and registration a new baseline MR/CT is required.
* The same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement.
* Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply:
* They have recovered from the effects of surgery.
* Residual disease following resection of recurrent tumor is not mandated for eligibility into the study.
* To best assess the extent of residual disease post-operatively, a CT/ MRI should be done:
* no later than 96 hours in the immediate post-operative period or
* at least 4 weeks post-operatively, and
* within 14 days of registration, and
* on a steroid dosage that has been stable for at least 5 days.
* If the 96 hour scan is more than 21 days before registration, the scan needs to be repeated.
* If the steroid dose is increased between the date of imaging and registration, a new baseline MRI/CT is required on a stable steroid dosage for at least 5 days.
* Patients must have progressed after radiation therapy and must have an interval of greater than or equal to 4 weeks from the completion of radiation therapy to study entry.
* All patients must sign an informed consent indicating that they are aware of the investigational nature of this study.
* Patients must be greater than or equal to 18 years old,
* and with a life expectancy greater than 8 weeks.
* Patients must have a Karnofsky performance status of greater than or equal to 60.
* Patients must have recovered from the toxic effects of prior therapy:
* 2 weeks from any investigational agent,
* 4 weeks from prior cytotoxic therapy,
* two weeks from vincristine,
* 6 weeks from nitrosoureas,
* 3 weeks from procarbazine administration,
* and 1 week for non-cytotoxic agents, e.g., interferon,
* tamoxifen,
* thalidomide,
* cis-retinoic acid, etc. (radiosensitizer does not count).
* Any questions related to the definition of non-cytotoxic agents should be directed to the Study Chair.
* Patients must have adequate bone marrow function (white blood count (WBC) -greater than or equal to 3,000/microliters,
* absolute neutrophil count (ANC) greater than or equal to 1,500/mm\^3,
* platelet count of greater than or equal to 100,000/mm\^3,
* and hemoglobin greater than or equal to 10 gm/dl),
* adequate liver function (serum glutamic oxaloacetic transaminase (SGOT) and -bilirubin less than 2 times upper limit of normal (ULN)),
* and adequate renal function (creatinine less than 1.5 mg/dL and/or creatinine -clearance greater than or equal to 60 cc/min) before starting therapy.
* These tests must be performed within 14 days prior to registration. -Eligibility level for hemoglobin may be reached by transfusion.
* Patients must not have any 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
* This study was designed to include women and minorities, but was not designed to measure differences of intervention effects.
* Males and females will be recruited with no preference to gender.
* No exclusion to this study will be based on race.
* Minorities will actively be recruited to participate.
* Urine protein should be screened by dipstick or urine analysis for Urine Protein Creatinine (UPC) ratio.
* For proteinuria greater than or equal to 1+ or urine protein:
* creatinine UPC ratio greater than 1.0,
* 24-hour urine protein should be obtained and the level should be less than 1000 mg for patient enrollment.
* Patients must practice adequate contraception

EXCLUSION CRITERIA:

* Patients who, in the view of the treating physician,
* have significant active cardiac,
* hepatic,
* renal,
* or psychiatric diseases are ineligible.
* No concurrent use of other standard chemotherapeutics or investigative agents.
* Patients known to have a malignancy that has required treatment in the last 12 months and/or is expected to require treatment in the next 12 months (except non-melanoma skin cancer or carcinoma in-situ in the cervix).
* Patients who have an active infection.
* Pregnant (positive pregnancy test) or nursing women.
* Both fertile men and women must agree to use adequate contraceptive measures during study therapy and for at least 6 months after the completion of bevacizumab therapy.
* Patients who have any disease that will obscure toxicity.
* Patients with evidence of acute intracranial/intratumoral hemorrhage on pre-study CT scan.
* Concurrent anti-coagulation or anti-platelet medication (including aspirin, -non-steroidal anti-inflammatories,
* cyclooxygenase 2 (COX-2) inhibitors).
* Serious or non-healing wound,
* ulcer
* or bone fracture
* History of abdominal fistula,
* gastrointestinal perforation
* or intra-abdominal abscess within 28 days
* Invasive procedures defined as follows:
* Major surgical procedure,
* open biopsy
* or significant traumatic injury within 28 days prior to Day 1 therapy
* Anticipation of need for major surgical procedures during the course of the study
* Core biopsy within 7 days prior to day 1 (D1) therapy
* Patients with clinically significant cardiovascular disease
* History of cerebrovascular accident (CVA) within 6 months
* Uncontrolled hypertension (greater than 150/100 mmHg)
* Myocardial infarction or unstable angina within 6 months
* New York Heart Association grade II or greater congestive heart failure
* Serious cardiac arrhythmia requiring medication
* Unstable angina pectoris
* Clinically significant peripheral vascular disease
* Evidence of bleeding diathesis or coagulopathy
* Prothrombin time (PT) international normalized ratio (INR) greater than 1.5
* Patients with known hypersensitivity of Chinese hamster ovary cell products or other recombinant human antibodies