Clinical trial NCT00393094
Conditions: High-Grade Gliomas
Keywords: Brain Tumor Chemotherapy Progression Radiotherapy Antiangiogenesis Glioma
Sponsor: National Cancer Institute (NCI)
Start date: 2006-09-01; Completion date: 2010-03-01
Enrollment: 31 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief 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

Detailed 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.

Arms: arm 1: Bevacizumab - 10 mg/kg intravenous injection Irinotecan - 125 mg/m\^2 if patient is on a non-enzyme inducing anti-epileptic drugs 340 mg/m\^2 if patient is on enzyme inducing anti-epileptic drugs every two weeks on a 4 week cycle
Interventions: intervention 1: Bevacizumab intervention 2: Irinotecan hydrochloride
Intervention descriptions: intervention 1: 10 mg/kg intravenous injection intervention 2: 125 mg/m\^2 if patient is on a non-enzyme inducing anti-epileptic drugs 340 mg/m\^2 if patient is on enzyme inducing anti-epileptic drugs every two weeks on a 4 week cycle

Protocol documents: