Bevacizumab and Irinotecan to Treat Brain Tumors

High-Grade Gliomas Clinical Trial

Official title: A Phase II Trial of Bevacizumab and Irinotecan for Patients With Recurrent High-Grade Gliomas Immediately Following Tumor Progression After Treatment w/Bevacizumab Alone: A Companion Trial to NCI Study 06-C-0064 (NCT00271609)(Bevacizumab Alone for Recurrent Gliomas)

Status Terminated

Clinical Trial Summary

Background:

• Bevacizumab is a genetically engineered antibody that blocks the growth of new blood vessels in tumors. It has shown activity against human brain tumors in laboratory tests and human clinical trials.

• Irinotecan causes damage to the deoxyribonucleic acid (DNA) in cancer cells so that the cells cannot reproduce or repair themselves. It is approved for treating patients with colorectal cancer.

• Bevacizumab and irinotecan in combination are more effective against colon cancer than either drug alone.

Objectives:

• To determine the safety of bevacizumab and irinotecan and any side effects associated with the combination of the two drugs when given to patients with high grade gliomas.

• To determine if the combination of bevacizumab and irinotecan can help patients with brain tumors that have grown after treatment with bevacizumab alone.

Eligibility:

-Patients 18 years of age and older who have been treated on National Cancer Institute (NCI) trial 06-C-0064 (NCT00271609), "Bevacizumab Alone for Recurrent Gliomas," and whose tumor has progressed.

Design:

Participants receive infusions of bevacizumab and irinotecan through a vein once every 2 weeks in 4-week treatment cycles, plus the following procedures:

• History, physical and neurological examinations every 2 weeks for the first treatment cycle and then every 4 weeks

• Magnetic Resonance Imaging (MRI) scan of the head every 4 weeks.

• Routine lab every week.

• Quality-of-life questionnaire every 4 weeks

Clinical Trial Description

Background:

• Bevacizumab is a humanized IgG1 monoclonal antibody (MAb) that binds all biologically active isoforms of human vascular endothelial growth factor (VEGF, or VEGF-A) with high affinity (kd = 1.1 nM ). The antibody consists of a human IgG1 framework and the antigen-binding complementarity-determining regions from the murine anti-VEGF MAb A.4.6.1.

• Irinotecan is a semisynthetic derivative of camptothecin that possesses greater aqueous solubility, greater in vitro and in vivo activity, and is associated with less severe and more predictable toxicity than camptothecin.

• We now propose treating patients whose tumors progress on our bevacizumab alone protocol with the combination of bevacizumab with irinotecan. We believe that this trial design has significant power to detect a true synergistic effect between the two agents given that the single agent activity of irinotecan is so low in patients with recurrent malignant gliomas (2-5% response rate) and the patients being treated on this trial will have tumors that have already progressed through bevacizumab.

Objective:

• To establish data and safety regarding the anti-tumor activity of bevacizumab plus irinotecan in patients with recurrent high-grade gliomas that have progressed on bevacizumab alone as determined by objective radiographic response rate.

• To determine the 6 month progression-free survival of treated patients and to characterize the pattern of changes in the number of endothelial progenitor cells over time and across patients.

• To obtain preliminary data regarding how response to treatment (stable disease or radiographic response) effects monthly measurements of quality of life while on study.

Eligibility:

• Patients must have been treated on the National Cancer Institute (NCI) trial 06-C-0064; bevacizumab alone for recurrent gliomas and now have evidence for tumor progression by magnetic resonance imaging (MRI) scan.

• Patients with histologically proven intracranial malignant glioma.

Design:

-Patients will be treated with bevacizumab by intravenous injection at a dose of 10mg/kg and irinotecan at a dose of 125 mg/m^2 for patients on non-enzyme-inducing anti-epileptic drugs (NEIAED) and 340 mg/m^2 for patients on enzyme-inducing anti-epileptic drugs (EIAED) every two weeks on a 4-week cycle. ;

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glioma
• High-Grade Gliomas

• NCT number: NCT00393094
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Terminated
• Phase: Phase 2
• Start date: September 2006
• Completion date: March 2010