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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00352521
First received: July 13, 2006
Last updated: July 18, 2014
Last verified: February 2013
  Purpose

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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Dynamic Contrast-Enhanced Magnetic Resonance Imaging With Bevacizumab in Combination With Irinotecan for Malignant Gliomas

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Correlation of the acute permeability and blood flow response (24-48 hours) with progression-free survival (PFS) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Assessed by DCE-MRI


Secondary Outcome Measures:
  • Overall Survival and Tumor Response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Incidence and severity of central nervous system (CNS) hemorrhage and systemic hemorrhage [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Enrollment: 20
Study Start Date: April 2006
Study Completion Date: July 2009
Primary Completion Date: December 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Avastin
Drug: irinotecan
Other Name: Camptosar
Procedure: dynamic contrast-enhanced magnetic resonance imaging

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00352521

Locations
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Investigators
Study Chair: James J. Vredenburgh, MD Duke Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00352521     History of Changes
Other Study ID Numbers: Pro00012387, DUMC-8053-05-12R0, CDR0000481476
Study First Received: July 13, 2006
Last Updated: July 18, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Duke University:
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

Additional relevant MeSH terms:
Glioma
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Irinotecan
Bevacizumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on September 11, 2014