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 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:
-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 (WBC greater than or equal to 3,000/microliters, ANC greater than or equal to 1,500/mm(3), platelet count of greatert than or equal to 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
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 than1000 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, 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 D1 therapy
Patients with clinically significant cardiovascular disease
-History of CVA within 6 months
-Uncontrolled hypertension (greater than150/100 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
PT INR greater than 1.5
Patients with known hypersensitivity of Chinese hamster ovary cell products or other recombinant human antibodies
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 01/13/2009