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

Primary Purpose

Newly Diagnosed High-Grade Gliomas, Diffuse Intrinsic Pontine Glioma

Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Temozolomide
Bevacizumab
Irinotecan
Sponsored by
Children's Hospital Medical Center, Cincinnati
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Newly Diagnosed High-Grade Gliomas

Eligibility Criteria

3 Years - 30 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Cincinnati Children's Hospital Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

HGG

DIPG

Arm Description

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

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

Outcomes

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

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
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
To estimate blood levels of VEGF in circulating endothelial cells in patients at different time points
To document changes in MR perfusion and diffusion within 24-48 hours after the 2nd dose of bevacizumab during radiotherapy
To correlate functional changes in tumor with responses to treatment using MR diffusion/perfusion imaging
To correlate the results of the biology studies in serum or tumor with PFS
To conduct gene expression profiling, CGH and SNP arrays in patients with high-grade gliomas
To assess telomerase activity, hTert expression, and telomere length in patients with high-grade gliomas
To assess the health-related quality of life of patients by parent report, and when possible, patient report at key points in therapy
To assess functional abilities and level of independence of patients during and following treatment

Full Information

First Posted
April 29, 2009
Last Updated
May 1, 2018
Sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00890786
Brief Title
A Study of Bevacizumab Therapy in Patients With Newly Diagnosed High-Grade Gliomas and Diffuse Intrinsic Pontine Gliomas
Official Title
A Pilot Study of Bevacizumab-Based Therapy in Patients With Newly Diagnosed High-Grade Gliomas and Diffuse Intrinsic Pontine Gliomas
Study Type
Interventional

2. Study Status

Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
May 2009 (undefined)
Primary Completion Date
October 2014 (Actual)
Study Completion Date
December 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
Genentech, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Newly Diagnosed High-Grade Gliomas, Diffuse Intrinsic Pontine Glioma

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
HGG
Arm Type
Experimental
Arm Description
Temozolomide, Bevacizumab, and Irinotecan according to the treatment schedule in the intervention section.
Arm Title
DIPG
Arm Type
Experimental
Arm Description
Temozolomide, Bevacizumab, and Irinotecan according to the treatment schedule in the interventions section.
Intervention Type
Drug
Intervention Name(s)
Temozolomide
Other Intervention Name(s)
Temodar
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Other Intervention Name(s)
Camptosar
Intervention Description
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 Outcome Measure Information:
Title
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 Outcome Measure Information:
Title
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
Title
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
Title
To estimate blood levels of VEGF in circulating endothelial cells in patients at different time points
Time Frame
2-3 years
Title
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
Title
To correlate functional changes in tumor with responses to treatment using MR diffusion/perfusion imaging
Time Frame
2-3 years
Title
To correlate the results of the biology studies in serum or tumor with PFS
Time Frame
2-3 years
Title
To conduct gene expression profiling, CGH and SNP arrays in patients with high-grade gliomas
Time Frame
2-3 years
Title
To assess telomerase activity, hTert expression, and telomere length in patients with high-grade gliomas
Time Frame
2-3 years
Title
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
Title
To assess functional abilities and level of independence of patients during and following treatment
Time Frame
2-3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maryam Fouladi, MD
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ann & Robert H. Lurie Children's Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60614
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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