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

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

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.

Study Overview

• Status: Completed
• Conditions: Brain and Central Nervous System Tumors
• Intervention / Treatment: Procedure: dynamic contrast-enhanced magnetic resonance imaging; Drug: bevacizumab; Drug: irinotecan

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 Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

Procedure: dynamic contrast-enhanced magnetic resonance imaging; Drug: bevacizumab; Other Names: Avastin; Drug: irinotecan; Other Names: Camptosar

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: James J. Vredenburgh, MD, Duke Cancer Institute

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): December 1, 2006
• Study Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: July 13, 2006
• First Submitted That Met QC Criteria: July 13, 2006
• First Posted (Estimate): July 14, 2006

Study Record Updates

• Last Update Posted (Estimate): July 22, 2014
• Last Update Submitted That Met QC Criteria: July 18, 2014
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma; recurrent adult brain tumor; adult anaplastic astrocytoma; adult anaplastic ependymoma; adult anaplastic oligodendroglioma; adult mixed glioma; adult pineal gland astrocytoma
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma; Nervous System Neoplasms; Central Nervous System Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Topoisomerase I Inhibitors; Bevacizumab; Irinotecan
• Other Study ID Numbers: Pro00012387; DUMC-8053-05-12R0; CDR0000481476 (Other Identifier: NCI)