Clinical trial NCT00271609
Conditions: Recurrent High-Grade Gliomas Malignant Gliomas
Keywords: AVASTIN Recurrence Chemotherapy Anti-Angiogenesis Radiotherapy Brain Tumor Malignant Glioma
Sponsor: National Cancer Institute (NCI)
Start date: 2005-12-01; Completion date: 2014-02-01
Enrollment: 88 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Background:

Bevacizumab is a genetically engineered antibody that blocks the growth of new blood vessels in tumors. Inhibiting the formation of these blood vessels may slow or stop disease progression by diminishing the supply of life-sustaining nutrients and oxygen the blood delivers to the tumor.

Bevacizumab is approved for treating colorectal cancer and has shown activity against brain tumor cells in laboratory and animal tests.

Objectives:

To examine the safety and side effects of bevacizumab in patients with recurrent brain tumors.

To determine the anti-tumor activity of bevacizumab in patients with recurrent brain tumors.

Eligibility:

Patients 18 years of age and older with a brain tumor that continues to grow after receiving standard treatments.

Design:

Patients complete the following procedures during the study:

* Infusions of bevacizumab through a vein once every 2 weeks in 4-week treatment cycles.
* Positron emission tomography (PET) scan before the first dose of bevacizumab, at the end of the first treatment cycle, and as needed after that.
* Magnetic resonance imaging (MRI) scan before the first dose of bevacizumab, within 48-96 hours after the first dose of bevacizumab in the first treatment cycle, and then every 4 weeks. One tube of blood for research is collected at the time of each MRI scan to look at specific cells.
* Physical and neurological examinations every 2 weeks for the first treatment cycle and then every 4 weeks.
* Quality-of-life questionnaires every 4 weeks.

Detailed description:
Background

* In vivo experiments have documented the ability of anti-vascular endothelial growth factor (VEGF) antibodies like bevacizumab to inhibit tumor growth in various preclinical tumor models, including gliomas.
* Given the pronounced neovasculature associated with over-expression of VEGF in malignant gliomas, and abundant published data demonstrating the dependence of glioma growth on the maintenance and proliferation of this neovasculature, bevacizumab represents a potentially promising new therapeutic approach to these otherwise refractory tumors.

Objective

* To establish data regarding the anti-tumor activity of bevacizumab in patients with recurrent high-grade gliomas as determined by progression-free-survival.
* To obtain information regarding the safety of bevacizumab administered to patients with recurrent high-grade gliomas.

Eligibility

* Adult patients with histologically proven intracranial malignant glioma
* Patients must have evidence for tumor progression by magnetic resonance imaging (MRI) scan
* Patients must have progressed after radiation therapy and must have an interval of greater than or equal to 4 weeks from the completion of radiation therapy to study entry

Design

* Patients will be treated with bevacizumab by intravenous injection at a dose of 10mg/kg every two weeks on a 4-week cycle.
* Prior to the first dose of bevacizumab and at the completion of the first 4-weeks of treatment, patients will undergo a fludeoxyglucose 18F -positron emission tomography (FDG-PET) scan (in cycle one only and then as needed) and a MRI perfusion scan.
* Peripheral blood circulating endothelial progenitor cells will be collected at the time of each MRI-perfusion scan. Additionally, patients will undergo a MRI perfusion scan within 48-96 hours of their first dose of bevacizumab (in cycle one only).
* For patients who are clinically/neurologically stable and with stable or responding radiographic disease at the end of each treatment cycle, treatment will continue with bevacizumab every 2 weeks, repeating MRI-perfusion scans at the conclusion (e.g. prior to another administration of bevacizumab) of each 4 week cycle.

A total of 88 patients will be enrolled on this study.

Arms: arm 1: Anaplastic astrocytoma Anaplastic oligodendroglioma Anaplastic mixed oligoastrocytoma Malignant astrocytoma (not otherwise specified) 10 mg/kg intravenously over 90 minutes every 2 weeks on a 28 day cycle. First dose is given over 90 minutes and subsequent doses are given over 30 minutes. arm 2: Glioblastoma multiforme Gliosarcoma 10 mg/kg intravenously over 90 minutes every 2 weeks on a 28 day cycle. First dose is given over 90 minutes and subsequent doses are given over 30 minutes.
Interventions: intervention 1: Bevacizumab
Intervention descriptions: intervention 1: 10 mg/kg intravenously over 90 minutes every 2 weeks on a 28 day cycle. First dose is given over 90 minutes and subsequent doses are given over 30 minutes.

Protocol documents: