Bevacizumab in Treating Patients With Recurrent or Progressive Glioma

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. PURPOSE: This phase II trial is studying how well bevacizumab works in treating patients with recurrent or progressive glioma.

Detailed Description
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OBJECTIVES: Determine the safety of single-agent bevacizumab in the treatment of patients with recurrent or progressive malignant glioma. Determine the efficacy of bevacizumab, in terms of progression-free survival at 6 months, in these patients. Assess changes in tumoral blood flow based on magnetic resonance (MR) perfusion and tissue changes by MR spectroscopy. OUTLINE: This is a pilot study. Patients receive bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 55 patients will be accrued for this study.

Official Title
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A Phase II Safety Study of Bevacizumab in Patients With Multiple Recurrent or Progressive Malignant Gliomas

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Biological: bevacizumab


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed malignant glioma, including the following: Glioblastoma multiforme Gliosarcoma Anaplastic astrocytoma or anaplastic glioma Malignant glioma not otherwise specified Evidence of tumor recurrence or progression by MRI or CT scan with contrast CT scan or MRI must be performed ≤ 96 hours post-operatively (≤ 2 weeks prior to study registration) or 4-6 weeks post-operatively to assess residual disease in patients who have undergone recent resection of recurrent or progressive tumor Steroid dosage must have been stable for ≥ 5 days Failed ≥ 1 prior systemic treatment with chemotherapy or biologic agents (excluding polifeprosan 20 with carmustine implant [Gliadel wafers]) Failed prior external-beam radiotherapy If received prior interstitial brachytherapy or stereotactic radiosurgery, true progressive disease (rather than radiation necrosis) must be confirmed by positron emission tomography, single-photon emission computer tomography with thallium, magnetic resonance (MR) spectroscopy, MR perfusion, or surgical documentation PATIENT CHARACTERISTICS: Karnofsky performance status 70-100% Life expectancy > 8 weeks WBC > 3,000/mm³ Absolute neutrophil count > 1,500/mm³ Platelet count > 100,000/mm³ Hemoglobin > 10 g/dL (transfusion allowed) SGOT and SGPT < 1.5 times upper limit of normal (ULN) Bilirubin < 1.5 times ULN Creatinine < 1.5 mg/dL Blood pressure ≤ 150/100 mm Hg No unstable angina No New York Heart Association class II-IV congestive heart failure No stroke or myocardial infarction within the past 6 months No clinically significant peripheral vascular disease No evidence of bleeding diathesis or coagulopathy Urine protein:creatinine ratio < 1.0 No significant medical illness that would preclude study participation or cannot be adequately controlled with appropriate therapy No other serious medical illness or infection No disease that would obscure toxicity or dangerously alter drug metabolism No significant traumatic injury within the past 28 days No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months No serious, nonhealing wound, ulcer, or bone fracture No history of any other cancer (except nonmelanoma skin cancer or carcinoma in situ of the cervix) unless cancer is in complete remission and patient is off all therapy for that cancer for ≥ 3 years Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: See Disease Characteristics More than 4 weeks since prior surgery for recurrent or progressive disease and recovered More than 28 days since prior major surgical procedure or open biopsy At least 4 weeks since prior cytotoxic therapy (6 weeks for nitrosoureas) At least 2 weeks since prior vincristine At least 3 weeks since prior procarbazine hydrochloride At least 1 week since prior noncytotoxic agents (e.g., interferon, tamoxifen, thalidomide, or isotretinoin) Radiosensitizer does not count At least 4 weeks since prior experimental biologic agents (e.g., epidermal growth factor receptor [EGFR] inhibitors) More than 7 days since prior minor surgery, such as fine-needle aspirations or core biopsies No concurrent combination anti-retroviral therapy for HIV-positive patients No concurrent enzyme-inducing anticonvulsants (EIACs) Patients on EIACs must switch to nonenzyme-inducing convulsants ≥ 2 weeks prior to study enrollment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Avastin<br> | Biological: bevacizumab<br>* Bevacizumab 15 mg/kg every 3 weeks over 30 to 90 minutes. One cycle = 3 weeks. Treatment continues until progressive disease or unacceptable toxicity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of Treatment | Safety of treatment will be defined by the number of patients that experience grade 3 and 4 adverse events where causal relationship with bevacizumab cannot be completely ruled out. Adverse events will be graded using Common Terminology Criteria for Adverse Events v3.0 (CTCAE) where: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE | From treatment initiation, throughout treatment and up to 30 days post-treatment, for up to 1 year. | 
| Progression-free Survival at 6 Months | The number of patients experiencing progression free survival (PFS) was calculated at the 6-month time point. | After all patients have surpassed the 6 month post-treatment timepoint | 
| Tumoral Blood Flow Changes | To assess changes in tumoral blood flow based on MR Perfusion and tissue changes by MR spectroscopy. | Before and after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult glioblastoma, adult gliosarcoma, recurrent adult brain tumor, adult anaplastic astrocytoma, adult giant cell glioblastoma