- INCLUSION CRITERIA:
- Patients with histologically proven intracranial malignant glioma will be eligible
for this protocol.
- Malignant glioma include glioblastoma multiforme (GBM),
- 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
- 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
- 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
- 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,
- 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
- Patients who, in the view of the treating physician,
- have significant active cardiac,
- 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
- Concurrent anti-coagulation or anti-platelet medication (including aspirin,
- cyclooxygenase 2 (COX-2) inhibitors).
- Serious or non-healing wound,
- 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