Medpedia

• Newly Diagnosed High-Grade Gliomas
• Diffuse Intrinsic Pontine Glioma

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.

• 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.
• 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).
• 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).

• 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
  Safety Issue: Yes
• 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
  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
  2-3 years
  Safety Issue: No
• To estimate blood levels of VEGF in circulating endothelial cells in patients at different time points
  2-3 years
  Safety Issue: No
• To document changes in MR perfusion and diffusion within 24-48 hours after the 2nd dose of bevacizumab during radiotherapy
  2-3 years
  Safety Issue: No
• To correlate functional changes in tumor with responses to treatment using MR diffusion/perfusion imaging
  2-3 years
  Safety Issue: No
• To correlate the results of the biology studies in serum or tumor with PFS
  2-3 years
  Safety Issue: No
• To conduct gene expression profiling, CGH and SNP arrays in patients with high-grade gliomas
  2-3 years
  Safety Issue: No
• To assess telomerase activity, hTert expression, and telomere length in patients with high-grade gliomas
  2-3 years
  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
  2-3 years
  Safety Issue: No
• To assess functional abilities and level of independence of patients during and following treatment
  2-3 years
  Safety Issue: No

• Maryam Fouladi, MD
  Principal Investigator, Children's Hospital Medical Center, Cincinnati

• Cincinnati Children's Hospital Medical Center
  Cincinnati, Ohio, 45229, United States
  Recruiting
  Rebecca Turner, MS, CCRP

  (513) 636-2799

  Rebecca.Turner@cchmc.org
• Cincinnati Children's Hospital Medical Center
  Cincinnati, Ohio, 45229, United States
  Recruiting

• Children's Hospital Medical Center, Cincinnati
  Lead Sponsor
• United States: Institutional Review Board