Overview

This trial is active, not recruiting.

Conditions newly diagnosed high-grade gliomas, diffuse intrinsic pontine glioma
Treatments temozolomide, bevacizumab, irinotecan
Phase phase 0
Target VEGF
Sponsor Children's Hospital Medical Center, Cincinnati
Collaborator Genentech, Inc.
Start date May 2009
End date October 2014
Trial size 27 participants
Trial identifier NCT00890786, HGG

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Temozolomide, Bevacizumab, and Irinotecan according to the treatment schedule in the intervention section.
temozolomide Temodar
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.
bevacizumab Avastin
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).
irinotecan Camptosar
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).
(Experimental)
Temozolomide, Bevacizumab, and Irinotecan according to the treatment schedule in the interventions section.
temozolomide Temodar
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.
bevacizumab Avastin
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).
irinotecan Camptosar
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).

Primary Outcomes

Measure
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

Secondary Outcomes

Measure
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
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

Eligibility Criteria

Male or female participants from 3 years up to 30 years old.

Inclusion Criteria: - Patients must be ≥ 3 years of age and ≤ 30 years of age at the time of study entry. - Diagnosis: - High-grade glioma;Patients must have had histologically verified anaplastic astrocytoma, glioblastoma multiforme or gliosarcoma.Patients with primary spinal cord tumors are eligible. - Diffuse intrinsic pontine glioma (DIPG) are eligible. - Performance Level: Karnofsky ≥ 50% for patients > 10 years of age and Lansky ≥ 50 for patients ≤ 10 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. - Prior Therapy: no prior anticancer therapy. - Concomitant Medications: The use of steroids is permissible. - Organ Function Requirements All patients must have adequate organ function as defined below. - Adequate Bone Marrow Function - Adequate Renal Function - Adequate Liver Function - Adequate Blood Clotting Defined As: INR, Fibrinogen, and PTT < Grade 2 - Central nervous system function. Patients with seizures may be enrolled if the seizures are well-controlled with non-enzyme inducing anticonvulsants. - Informed Consent. Patients and/or parents/legal guardians must have signed an informed consent. Exclusion Criteria: - Patients with metastatic disease (i.e. M+ disease, or disease anywhere other than primary site). - Patients with evidence of a new intracranial hemorrhage that is larger than a punctate size on baseline MRI scan. - Allergies: Patients with a history of allergic reaction to Chinese hamster ovary cell products, or other recombinant human antibodies. - Pregnant or breast feeding women will not be entered on this study. - Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study. - Infection: Patients who require IV antibiotics at time of enrollment, or who are currently receiving treatment for Clostridium difficile infection are excluded. - Thrombosis: Patients must not have been previously diagnosed with a deep venous or arterial thrombosis (including pulmonary embolism), and must not have a known thrombophilic condition. - Serious or Non-Healing Wounds - Surgical Procedures: Patients who have had major surgery should not receive the first dose of bevacizumab until 28 days after major surgery. - Patients with uncontrolled systemic hypertension. - Proteinuria with a urine protein (albumin)/creatinine ratio of ≥1.0.

Additional Information

Official title A Pilot Study of Bevacizumab-Based Therapy in Patients With Newly Diagnosed High-Grade Gliomas and Diffuse Intrinsic Pontine Gliomas
Principal investigator Maryam Fouladi, MD
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by Children's Hospital Medical Center, Cincinnati.