MRI in Patients Receiving Bevacizumab and Irinotecan for Recurrent Malignant Glioma

• Reproducibility of dynamic contrast-enhanced (DCE)-MRI [ Designated as safety issue: No ]
• Predictive value of DCE-MRI [ Designated as safety issue: No ]
• Response rate [ Designated as safety issue: No ]
• Progression-free survival [ Designated as safety issue: No ]
• Toxicity [ Designated as safety issue: Yes ]

• Reproducibility of dynamic contrast-enhanced (DCE)-MRI
• Predictive value of DCE-MRI
• Response rate
• Progression-free survival
• Toxicity

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.

OBJECTIVES:

Primary

• Examine the effect of bevacizumab and irinotecan hydrochloride on tumor vascular permeability and blood flow in patients with recurrent malignant gliomas.

Secondary

• Determine the reproducibility of dynamic contrast-enhanced (DCE)-MRI in these patients.
• Determine the predictive value of DCE-MRI in patients treated with bevacizumab and irinotecan hydrochloride.
• Describe the activity of this regimen, as measured by response rate and progression-free survival, in these patients.
• Describe the toxicity associated with this regimen.

OUTLINE: Patients receive bevacizumab IV and irinotecan IV 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.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

• Biological: bevacizumab
• Drug: irinotecan hydrochloride
• Procedure: dynamic contrast-enhanced magnetic resonance imaging

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