The outcome for children with high-grade gliomas and diffuse intrinsic brainstem gliomas remains poor despite the use of multi-modal therapy with surgery, radiation therapy and chemotherapy.
Novel therapies are needed to improve the outcome of these children. Recent studies have demonstrated very promising results of treatment with bevacizumab/irinotecan in patients with recurrent high grade gliomas. Based on these promising results, and the tolerability of the irinotecan and bevacizumab in children with recurrent CNS malignancies both anecdotally and in a study conducted by the Pediatric Brain Tumor Consortium, we have designed a novel study incorporating concurrent radiation therapy with bevacizumab ± temozolomide followed by bevacizumab, irinotecan ±temozolomide in patients with newly diagnosed high-grade gliomas and diffuse intrinsic pontine gliomas.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
27
High Grade Glioma Temozolomide during radiotherapy: 90mg/m2/day PO daily (for patients ≤ 18 years of age); 75mg/m2/day PO daily (for patients ≥ 19 years of age); must begin by Day 5 of radiotherapy for a total of 42 days consecutively. High Grade Glioma Temozolomide during maintenance chemotherapy: 150mg/m2/day PO on Days 1-5.
High Grade Glioma Bevacizumab during radiotherapy: 10 mg/kg as a 90 minute infusion on Day 22 (± 2 days)and Day 36 (± 2 days) of radiotherapy. High Grade Glioma Bevacizumab during maintenance chemotherapy:10 mg/kg as a 90 minute infusion on Day 1 (+ 2 days)and Day 15 (± 2 days) of each course. Diffuse Intrinsic Pontine Gliomas Bevacizumab during radiotherapy: 10 mg/kg as a 90 minute infusion on Days 1 (+ 2 days),15, 29, and 43(±2 days for all 3 doses) of radiotherapy. Diffuse Intrinsic Pontine Gliomas Bevacizumab during maintenance chemotherapy: 10 mg/kg as a 90 minute infusion on Day 1 (+2 days)and 15 (±2 days).
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
To determine the toxicities and feasibility of the proposed treatment regimen in patients with high-grade glioma and diffuse intrinsic brainstem glioma
Time frame: 2-3 years
To determine 1-year EFS, median PFS and median OS in newly diagnosed patients with high-grade glioma treated with radiotherapy and concurrent temozolomide, bevacizumab followed by bevacizumab, irinotecan and temozolomide for 12 courses
Time frame: 2-3 years
To determine the 1-year EFS, median PFS and median OS in newly diagnosed patients with diffuse intrinsic brainstem glioma treated with radiotherapy and concurrent bevacizumab followed by bevacizumab and irinotecan for 12 courses
Time frame: 2-3 years
To estimate blood levels of VEGF in circulating endothelial cells in patients at different time points
Time frame: 2-3 years
To document changes in MR perfusion and diffusion within 24-48 hours after the 2nd dose of bevacizumab during radiotherapy
Time frame: 2-3 years
To correlate functional changes in tumor with responses to treatment using MR diffusion/perfusion imaging
Time frame: 2-3 years
To correlate the results of the biology studies in serum or tumor with PFS
Time frame: 2-3 years
To conduct gene expression profiling, CGH and SNP arrays in patients with high-grade gliomas
Time frame: 2-3 years
To assess telomerase activity, hTert expression, and telomere length in patients with high-grade gliomas
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High Grade Glioma Irinotecan during maintenance chemotherapy:125 mg/m2/day IV over 90 minutes on Days 1 (+ 2 days)and 15 (±2 days) of each course, given no sooner than one hour after temozolomide on Day 1. Diffuse Intrinsic Pontine Gliomas Irinotecan maintenance chemotherapy: 125 mg/m2/day IV on Day 1 (+2 days)and Day 15 (±2 days).
Time frame: 2-3 years
To assess the health-related quality of life of patients by parent report, and when possible, patient report at key points in therapy
Time frame: 2-3 years
To assess functional abilities and level of independence of patients during and following treatment
Time frame: 2-3 years