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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00890786
Recruitment Status : Completed
First Posted : April 30, 2009
Last Update Posted : May 2, 2018
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

Tracking Information
First Submitted Date  ICMJE April 29, 2009
First Posted Date  ICMJE April 30, 2009
Last Update Posted Date May 2, 2018
Study Start Date  ICMJE May 2009
Actual Primary Completion Date October 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 29, 2009)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 1, 2009)
  • 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 ]
  • 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 ]
  • To estimate blood levels of VEGF in circulating endothelial cells in patients at different time points [ Time Frame: 2-3 years ]
  • 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 ]
  • To correlate functional changes in tumor with responses to treatment using MR diffusion/perfusion imaging [ Time Frame: 2-3 years ]
  • To correlate the results of the biology studies in serum or tumor with PFS [ Time Frame: 2-3 years ]
  • To conduct gene expression profiling, CGH and SNP arrays in patients with high-grade gliomas [ Time Frame: 2-3 years ]
  • To assess telomerase activity, hTert expression, and telomere length in patients with high-grade gliomas [ Time Frame: 2-3 years ]
  • 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 ]
  • To assess functional abilities and level of independence of patients during and following treatment [ Time Frame: 2-3 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 29, 2009)
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • To correlate functional changes in tumor with responses to treatment using MR diffusion/perfusion imaging [ Time Frame: 2-3 years ]
  • To correlate the results of the biology studies in serum or tumor with PFS [ Time Frame: 2-3 years ]
  • To conduct gene expression profiling, CGH and SNP arrays in patients with high-grade gliomas [ Time Frame: 2-3 years ]
  • To assess telomerase activity, hTert expression, and telomere length in patients with high-grade gliomas [ Time Frame: 2-3 years ]
  • 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 ]
  • To assess functional abilities and level of independence of patients during and following treatment [ Time Frame: 2-3 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Bevacizumab Therapy in Patients With Newly Diagnosed High-Grade Gliomas and Diffuse Intrinsic Pontine Gliomas
Official Title  ICMJE A Pilot Study of Bevacizumab-Based Therapy in Patients With Newly Diagnosed High-Grade Gliomas and Diffuse Intrinsic Pontine Gliomas
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Newly Diagnosed High-Grade Gliomas
  • Diffuse Intrinsic Pontine Glioma
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Experimental: HGG
    Temozolomide, Bevacizumab, and Irinotecan according to the treatment schedule in the intervention section.
    Interventions:
    • Drug: Temozolomide
    • Drug: Bevacizumab
    • Drug: Irinotecan
  • Experimental: DIPG
    Temozolomide, Bevacizumab, and Irinotecan according to the treatment schedule in the interventions section.
    Interventions:
    • Drug: Temozolomide
    • Drug: Bevacizumab
    • Drug: Irinotecan
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 22, 2016)
27
Original Estimated Enrollment  ICMJE
 (submitted: April 29, 2009)
20
Actual Study Completion Date  ICMJE December 2017
Actual Primary Completion Date October 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 3 Years to 30 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00890786
Other Study ID Numbers  ICMJE HGG
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Children's Hospital Medical Center, Cincinnati
Study Sponsor  ICMJE Children's Hospital Medical Center, Cincinnati
Collaborators  ICMJE Genentech, Inc.
Investigators  ICMJE
Principal Investigator: Maryam Fouladi, MD Children's Hospital Medical Center, Cincinnati
PRS Account Children's Hospital Medical Center, Cincinnati
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP