Clinical Trial Finder

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  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

Background.

• - In vivo experiments have documented the ability of anti-vascular endothelial growth factor (VEGF) antibodies like bevacizumab to inhibit tumor growth in various preclinical tumor models, including gliomas.

• - Given the pronounced neovasculature associated with over-expression of VEGF in malignant gliomas, and abundant published data demonstrating the dependence of glioma growth on the maintenance and proliferation of this neovasculature, bevacizumab represents a potentially promising new therapeutic approach to these otherwise refractory tumors.

Objective.

• - To establish data regarding the anti-tumor activity of bevacizumab in patients with recurrent high-grade gliomas as determined by progression-free-survival.

• - To obtain information regarding the safety of bevacizumab administered to patients with recurrent high-grade gliomas.

Eligibility.

• - Adult patients with histologically proven intracranial malignant glioma.

• - Patients must have evidence for tumor progression by magnetic resonance imaging (MRI) scan.

• - 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.

Design.

• - Patients will be treated with bevacizumab by intravenous injection at a dose of 10mg/kg every two weeks on a 4-week cycle.

• - Prior to the first dose of bevacizumab and at the completion of the first 4-weeks of treatment, patients will undergo a fludeoxyglucose 18F -positron emission tomography (FDG-PET) scan (in cycle one only and then as needed) and a MRI perfusion scan.

• - Peripheral blood circulating endothelial progenitor cells will be collected at the time of each MRI-perfusion scan.

Additionally, patients will undergo a MRI perfusion scan within 48-96 hours of their first dose of bevacizumab (in cycle one only).

• - For patients who are clinically/neurologically stable and with stable or responding radiographic disease at the end of each treatment cycle, treatment will continue with bevacizumab every 2 weeks, repeating MRI-perfusion scans at the conclusion (e.g. prior to another administration of bevacizumab) of each 4 week cycle.

A total of 88 patients will be enrolled on this study.

Arms

Other: Anaplastic Glioma (AG)

Anaplastic astrocytoma Anaplastic oligodendroglioma Anaplastic mixed oligoastrocytoma Malignant astrocytoma (not otherwise specified) 10 mg/kg intravenously over 90 minutes every 2 weeks on a 28 day cycle. First dose is given over 90 minutes and subsequent doses are given over 30 minutes.

Other: Glioblastoma Multiforme (GBM)

Glioblastoma multiforme Gliosarcoma 10 mg/kg intravenously over 90 minutes every 2 weeks on a 28 day cycle. First dose is given over 90 minutes and subsequent doses are given over 30 minutes.

Interventions

Drug: - Bevacizumab

10 mg/kg intravenously over 90 minutes every 2 weeks on a 28 day cycle. First dose is given over 90 minutes and subsequent doses are given over 30 minutes.