Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) With Bevacizumab and Irinotecan for Malignant 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 block blood flow to the tumor. Drugs used in chemotherapy, such as irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with irinotecan may kill more tumor cells. Diagnostic procedures, such as MRI, may help doctors predict a patient's response to treatment and help plan the best treatment. PURPOSE: This phase II trial is studying how well giving bevacizumab together with irinotecan works in treating patients with recurrent malignant glioma and how well MRI predicts response to treatment.

Detailed Description
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OBJECTIVES: Primary Examine the effect of bevacizumab and irinotecan on vascular permeability and blood flow in patients with recurrent malignant gliomas. Secondary Determine the reproducibility of dynamic contrast-enhanced (DCE-MRI) in malignant gliomas. Determine the predictive value of DCE-MRI in patients with recurrent malignant gliomas treated with bevacizumab and irinotecan. Describe the activity of the combination of bevacizumab with irinotecan as measured by response rate and progression-free survival. Describe the toxicity associated with the administration of bevacizumab with irinotecan. OUTLINE: Patients receive bevacizumab IV on days 1, 15, and 29 and irinotecan IV on days 2, 15, and 29 during the first 6-week cycle. After the first cycle, the irinotecan and bevacizumab will be given on days 1, 15 and 29. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo dynamic contrast-enhanced MRI 4 times.

Official Title
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Dynamic Contrast-Enhanced Magnetic Resonance Imaging With Bevacizumab in Combination With Irinotecan for Malignant Gliomas

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: bevacizumab
* Drug: irinotecan
* Procedure: dynamic contrast-enhanced magnetic resonance imaging


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of any of the following malignant gliomas: Glioblastoma multiforme Anaplastic astrocytoma Grade 3 or greater WHO astrocytic, oligodendroglial, or mixed glial tumors that were initially diagnosed by histologic examination of a tumor specimen obtained from biopsy or resection Recurrent disease No more than 3 prior recurrences Measurable recurrent or residual primary CNS neoplasm on contrast-enhanced MRI or CT scan No evidence of CNS hemorrhage on baseline MRI or CT scan PATIENT CHARACTERISTICS: Karnofsky performance status 60-100% Hematocrit > 29% Absolute neutrophil count > 1,500/mm³ Platelet count > 125,000/mm³ Creatinine < 1.5 mg/dL SGOT < 1.5 times upper limit of normal (ULN) Bilirubin < 1.5 times ULN Not pregnant or nursing Fertile patients must use effective contraception No active infection No significant traumatic injury within the past 28 days PRIOR CONCURRENT THERAPY: At least 6 weeks since prior surgical resection More than 28 days since prior major surgical procedure or open biopsy More than 7 days since prior minor surgical procedure, fine-needle aspirations, or core biopsies At least 6 weeks since prior chemotherapy* At least 4 weeks since prior radiotherapy* No concurrent immunosuppressive agents No concurrent therapeutic anticoagulation Concurrent corticosteroids allowed if dose has been stable for 1 week prior to study entry NOTE: * Unless there is unequivocal evidence of progressive disease

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: Bevacizumab and irinotecan<br>The bevacizumab will be dosed at 10 mg/kg every 14 days (days 1, 15 and 29) and the irinotecan on days 2, 15, and 29 of the first six week schedule. The irinotecan dose will depend on whether the patient is on an enzyme-inducing antiepileptic drug (EIAED). If the patient is on an EIAED, the patient will receive 340 mg/m2 on days 2, 15, and 29 of the first six week schedule. If the patient is not on an EIAED, the dose of irinotecan will be 125 mg/m2 on days 2, 15, and 29 of the first six week schedule. After the first cycle, the irinotecan and bevacizumab will be given on days 1, 15 and 29. | Drug: bevacizumab<br> <br> * Other names: Avastin;Drug: irinotecan<br> <br> * Other names: Camptosar;Procedure: dynamic contrast-enhanced magnetic resonance imaging<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of the acute permeability and blood flow response (24-48 hours) with progression-free survival (PFS) | Assessed by DCE-MRI | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival and Tumor Response |  | 2 years | 
| Incidence and severity of central nervous system (CNS) hemorrhage and systemic hemorrhage |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult anaplastic astrocytoma, adult mixed glioma, adult giant cell glioblastoma, adult gliosarcoma, recurrent adult brain tumor, adult glioblastoma, adult anaplastic ependymoma, adult anaplastic oligodendroglioma, adult pineal gland astrocytoma