INCLUSION CRITERIA:
-Patients with histologically proven intracranial malignant glioma will be eligible for this protocol. Malignant gliomas 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 MRI or 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:
a) They have recovered from the effects of surgery.
b) 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:
1. no later than 96 hours in the immediate postoperative period or
2. at least 4 weeks post-operatively, and
3. within 14 days of registration, and
4. 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 or their previously designated DPA (if the patient is deemed by the treating physician to be impaired or questionably impaired in such a way that the ability of the patient to give informed consent is questionable) 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, and 1 week for noncytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cisretinoic acid, etc. (radiosensitizer does not count). Any questions related to the definition of non-cytotoxic agents should be directed to the Principal Investigator.
-Patients must have adequate bone marrow function (WBC greater than or equal to 3,000/?l, ANC greater than or equal to 1,500/mm(3), platelet count of greater than 100,000/mm(3), and hemoglobin greater than or equal to 10 gm/dl), adequate liver function (SGOT and bilirubin less than 2 times 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
-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
-Head CT Scan without contrast (to rule out significant acute hemorrhage) within 7 days prior to starting treatment.
-Chest x-ray
-An echocardiogram to be performed within 14 days of registration.
-A 12 lead electrocardiogram (ECG) to be performed within 2 weeks of trial entry with QTc less than 460 msec.
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 (i.e. vasculitis, congentital hyopercoagubility syndromes, uncontrolled primary hypertension, idiopathic thrombocytopenia).
-Evidence of significant recent hemorrhage on mandatory CT scan (defined as 1 cm or more of acute blood) of the brain within 7 days of patient accrual with the following exceptions: resolving hemorrhagic changes related to surgery, and/or presence of punctate hemorrhages in the tumor.
-Concurrent anti-coagulation or anti-platelet medication (including aspirin, non-steroidal anti-inflammatories, COX-2 inhibitors).
-Serious or non-healing wound, ulcer or bone fracture
-History of abdominal fistula, gastrointestinal perforation or intraabdominal abscess within 6 months
-Invasive procedures defined as follows:
a. Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1 therapy
b. Anticipation of need for major surgical procedures during the course of the study
c. Core biopsy within 7 days prior to D1 therapy
-Patients with clinically significant cardiovascular disease
a. History of CVA or TIA within 6 months
b. Uncontrolled hypertension (greater than 150/100 mmHg) while on antihypertensive medications
c. Myocardial infarction or unstable angina within 6 months
d. New York heart association grade II or greater congestive heart failure
e. Serious cardiac arrhythmia requiring medication
f. Unstable angina pectoris
g. Clinically significant peripheral vascular disease
-Evidence of bleeding diathesis or coagulopathy
-PT INR greater than 1.5
-Patients with known hypersensitivity of Chinese hamster ovary cell products or other recombinant human antibodies
-QTc with Bazett's correction that is unmeasurable or greater than or equal to 460 msec on screening ECG. If a patient has QTc greater than or equal to 460 msec on screening ECG, a second screen ECG may be repeated at least 24 hours later. The average QTc from the 2 screening ECGs must be less than 460 msec in order for the patient to be eligible for the study.
-Patients with clinically significant pericardial effusion on mandatory echocardiogram.