Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) With Bevacizumab and Irinotecan for Malignant Glioma

Sponsor

Duke University (Other)

Overall Status

Completed

CT.gov ID

NCT00352521

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors	Drug: bevacizumab Drug: irinotecan Procedure: dynamic contrast-enhanced magnetic resonance imaging	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Apr 1, 2006

Actual Primary Completion Date :

Dec 1, 2006

Actual Study Completion Date :

Jul 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bevacizumab and irinotecan 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 Other Names: Avastin Drug: irinotecan Other Names: Camptosar Procedure: dynamic contrast-enhanced magnetic resonance imaging

Arm

Intervention/Treatment

Experimental: Bevacizumab and irinotecan

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

Other Names:

Avastin

Drug: irinotecan

Other Names:

Camptosar

Procedure: dynamic contrast-enhanced magnetic resonance imaging

Outcome Measures

Primary Outcome Measures

Correlation of the acute permeability and blood flow response (24-48 hours) with progression-free survival (PFS) [1 year]
Assessed by DCE-MRI

Secondary Outcome Measures

Overall Survival and Tumor Response [2 years]
Incidence and severity of central nervous system (CNS) hemorrhage and systemic hemorrhage [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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