A Study of Bevacizumab Therapy in Patients With Newly Diagnosed High-Grade Gliomas and Diffuse Intrinsic Pontine Gliomas - Full Text View

Sponsor:	Children's Hospital Medical Center, Cincinnati
Collaborator:	Genentech
Information provided by (Responsible Party):	Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier:	NCT00890786

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:	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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Temozolomide Irinotecan U 101440E Irinotecan hydrochloride Bevacizumab

U.S. FDA Resources

Further study details as provided by Children's Hospital Medical Center, Cincinnati:

Primary Outcome Measures:

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 ]

Secondary Outcome Measures:

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:	April 2012
Estimated Primary Completion Date:	April 2012 (Final data collection date for primary outcome measure)

Intervention Details:

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

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

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

Criteria

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00890786

Contacts

Contact: Rebecca Turner, MS, CCRP

513-636-2799

Rebecca.Turner@CCHMC.org

Locations

United States, Illinois
Children's Memorial Hospital	Recruiting
Chicago, Illinois, United States, 60614
Contact: Nicole Reinholdt 773-880-4708 nreinholdt@childrensmemorial.org
United States, Ohio
Cincinnati Children's Hospital Medical Center	Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Rebecca Turner, MS, CCRP 513-636-2799 Rebecca.Turner@cchmc.org

Sponsors and Collaborators

Children's Hospital Medical Center, Cincinnati

Genentech

Investigators

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:	February 9, 2012
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 February 09, 2012