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

Sponsors and Collaborators:	Children's Hospital Medical Center, Cincinnati Genentech
Information provided by:	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	Phase
Newly Diagnosed High-Grade Gliomas Diffuse Intrinsic Pontine Glioma	Drug: Temozolomide Drug: Bevacizumab Drug: Irinotecan	Phase I Phase II

MedlinePlus related topics: Cancer Radiation Therapy

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

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Pilot Study of Bevacizumab-Based Therapy in Patients With Newly Diagnosed High-Grade Gliomas and Diffuse Intrinsic Pontine Gliomas

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, BFGF, TSP-1, I-CAM, v-CAM and 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 with high-grade gliomas 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; 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 21 and Day 35 (+or-1 day) of radiotherapy.

High Grade Glioma Bevacizumab during maintenance chemotherapy:10 mg/kg as a 90 minute infusion on Day 1 and Day 15 (+or-1 day) of each course.

Diffuse Intrinsic Pontine Gliomas Bevacizumab during radiotherapy: 10 mg/kg as a 90 minute infusion on Days 1,15, 29, and 43(+or -1 day) of radiotherapy.

Diffuse Intrinsic Pontine Gliomas Bevacizumab during maintenance chemotherapy: 10 mg/kg as a 90 minute infusion on Day 1 and 15 (+or-1 day).

High Grade Glioma Irinotecan during maintenance chemotherapy:125 mg/m2/day IV over 90 minutes on Days 1 and 15 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 and Day 15.

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, Ohio
Cincinnati Children's Hospital Medical Center
3333 Burnet Avenue, Ohio, United States, 45229
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229

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:	CIncinnati Children's Hospital Medical Center ( Maryam Fouladi, MD )
Study ID Numbers:	HGG
Study First Received:	April 29, 2009
Last Updated:	May 4, 2009
ClinicalTrials.gov Identifier:	NCT00890786 History of Changes
Health Authority:	United States: Institutional Review Board

Study placed in the following topic categories:

Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Irinotecan
Neuroepithelioma
Antineoplastic Agents, Alkylating
Bevacizumab

Glioma
Angiogenesis Inhibitors
Antineoplastic Agents, Phytogenic
Alkylating Agents
Temozolomide
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Neoplasms, Nerve Tissue
Irinotecan
Enzyme Inhibitors
Bevacizumab
Angiogenesis Inhibitors
Temozolomide
Pharmacologic Actions

Neuroectodermal Tumors
Neoplasms
Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
Growth Inhibitors
Angiogenesis Modulating Agents
Glioma
Antineoplastic Agents, Alkylating
Neoplasms, Neuroepithelial
Antineoplastic Agents, Phytogenic
Alkylating Agents
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on May 07, 2009