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

NCT00890786 | Completed Early Phase 1 DMC

• 1 other identifier: HGG
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Newly Diagnosed High-Grade Gliomas; Diffuse Intrinsic Pontine Glioma

Outcome Measures

Primary Outcomes (1)

• To determine the toxicities and feasibility of the proposed treatment regimen in patients with high-grade glioma and diffuse intrinsic brainstem glioma

  2-3 years

Secondary Outcomes (10)

• 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

  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

  2-3 years

• To estimate blood levels of VEGF in circulating endothelial cells in patients at different time points

  2-3 years

• To document changes in MR perfusion and diffusion within 24-48 hours after the 2nd dose of bevacizumab during radiotherapy

  2-3 years

• To correlate functional changes in tumor with responses to treatment using MR diffusion/perfusion imaging

  2-3 years

Study Arms (2)

HGG

EXPERIMENTAL

Temozolomide, Bevacizumab, and Irinotecan according to the treatment schedule in the intervention section.

Drug: Temozolomide; Drug: Bevacizumab; Drug: Irinotecan

DIPG

EXPERIMENTAL

Temozolomide, Bevacizumab, and Irinotecan according to the treatment schedule in the interventions section.

Drug: Temozolomide; Drug: Bevacizumab; Drug: Irinotecan

Interventions

Temozolomide DRUG

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.

Also known as: Temodar

DIPG; HGG

Bevacizumab DRUG

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).

Also known as: Avastin

DIPG; HGG

Irinotecan DRUG

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).

Also known as: Camptosar

DIPG; HGG

Eligibility Criteria

• Age: 3 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• Genentech, Inc.: collaborator

Study Sites (2)

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60614, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Conditions

Diffuse Intrinsic Pontine Glioma

Interventions

Temozolomide; Bevacizumab; Irinotecan

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids

Study Officials

• Maryam Fouladi, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2009
• First Posted: April 30, 2009
• Study Start: May 1, 2009
• Primary Completion: October 1, 2014
• Study Completion: December 1, 2017
• Last Updated: May 2, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)