A Study of Bevacizumab Therapy in Patients With Newly Diagnosed High-Grade Gliomas and Diffuse Intrinsic Pontine Gliomas
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
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.
| Condition | Intervention |
|---|---|
|
Newly Diagnosed High-Grade Gliomas Diffuse Intrinsic Pontine Glioma |
Drug: Temozolomide Drug: Bevacizumab Drug: Irinotecan |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Pilot Study of Bevacizumab-Based Therapy in Patients With Newly Diagnosed High-Grade Gliomas and Diffuse Intrinsic Pontine Gliomas |
- 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 ] [ Designated as safety issue: Yes ]
- 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- To estimate blood levels of VEGF in circulating endothelial cells in patients at different time points [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- To correlate functional changes in tumor with responses to treatment using MR diffusion/perfusion imaging [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]
- To correlate the results of the biology studies in serum or tumor with PFS [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]
- To conduct gene expression profiling, CGH and SNP arrays in patients with high-grade gliomas [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]
- To assess telomerase activity, hTert expression, and telomere length in patients with high-grade gliomas [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- To assess functional abilities and level of independence of patients during and following treatment [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 35 |
| Study Start Date: | May 2009 |
| Estimated Study Completion Date: | September 2013 |
| Estimated Primary Completion Date: | September 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: HGG
Temozolomide, Bevacizumab, and Irinotecan according to the treatment schedule in the intervention section.
|
Drug: Temozolomide
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. Other Name: Temodar
Drug: Bevacizumab
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). Other Name: Avastin
Drug: Irinotecan
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). Other Name: Camptosar
|
|
Experimental: DIPG
Temozolomide, Bevacizumab, and Irinotecan according to the treatment schedule in the interventions section.
|
Drug: Temozolomide
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. Other Name: Temodar
Drug: Bevacizumab
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). Other Name: Avastin
Drug: Irinotecan
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). Other Name: Camptosar
|
Eligibility| Ages Eligible for Study: | 3 Years to 30 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations| Contact: Laura Mayer | 513-636-2799 | cancer@cchmc.org |
| United States, Illinois | |
| Ann & Robert H. Lurie Children's Hospital of Chicago | Recruiting |
| Chicago, Illinois, United States, 60614 | |
| Contact: Jillian Tabares 312-227-4810 JTabares@luriechildrens.org | |
| United States, Ohio | |
| Cincinnati Children's Hospital Medical Center | Recruiting |
| Cincinnati, Ohio, United States, 45229 | |
| Contact: Laura Mayer 513-636-2799 cancer@cchmc.org | |
| Principal Investigator: | Maryam Fouladi, MD | Children's Hospital Medical Center, Cincinnati |
More Information
No publications provided
| Responsible Party: | Children's Hospital Medical Center, Cincinnati |
| ClinicalTrials.gov Identifier: | NCT00890786 History of Changes |
| Other Study ID Numbers: | HGG |
| Study First Received: | April 29, 2009 |
| Last Updated: | May 7, 2013 |
| Health Authority: | United States: Institutional Review Board |
Additional relevant MeSH terms:
|
Glioma Pontine Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Astrocytoma Temozolomide Irinotecan Bevacizumab Antineoplastic Agents, Alkylating Alkylating Agents |
Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Antineoplastic Agents, Phytogenic Radiation-Sensitizing Agents Physiological Effects of Drugs Topoisomerase I Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Growth Inhibitors |
ClinicalTrials.gov processed this record on May 23, 2013