Title (COG ACNS0822) A Randomized Phase II/III Study of Vorinostat (IND #71976) and Local Irradiation OR Temozolomide and Local Irradiation OR Bevacizumab (IND# 7921) and Local Irradiation Followed by Maintenance Bevacizumab and Temozolomide in Children with Newly Diagnosed High-Grade Gliomas
Principal Investigator Martin Brecher, MD
Study Number 192411
Summary This protocol will study three agents’ roles as radiosensitizers. This study will be done in three parts: an initial feasibility study within the phase II part which will determine the dose of vorinostat that is safe and tolerable in combination with radiation therapy for patients less than 22 years of age; a phase II part will employ a randomized approach to determine if either of 2 experimental treatment arms (bevacizumab or vorinostat during chemoradiotherapy), have a higher nominal 1-year event-free survival (EFS) than the de facto standard treatment arm (temozolomide during chemoradiotherapy); and a randomized phase III part where patients will b randomized to either the chosen experimental arm or the temozolomide arm for a formal efficacy (EFS) comparison. EFS, PFS, and overall survival (OS) on each treatment arm will be estimated using Kaplan-Meier curves. All phases of this study, including the feasibility phase, will be available to all COG institutions.
- Patients must be greater than or equal to 3 years and less than 22 years at the time of enrollment.
- Patients must have a newly diagnosed high-grade glioma such as: anaplastic astrocytoma, glioblastoma multiforme, or gliosarcoma. Patients with primary spinal cord malignant gliomas are eligible. Patients with primary brainstem tumors are not eligible. Patients with a diagnosis of oligodendroglioma or oligoastrocytoma are NOT eligible.
- Patients must have histologic verification of diagnosis. CSF cytology must be done if clinically indicated.
- For patients with intracranial tumors, a pre-operative and post-operative brain MRI with and without gadolinium and a spine MRI if clinically indicated must be obtained. For patients with spinal cord primaries, only a pre and post-operative spine MRI with gadolinium must be obtained. The post-operative MRIs must be obtained within 4 weeks prior to enrollment onto study. The requirement for a post-operative MRI is waived for patients who undergo biopsy only (see Section 7.1)
- Patients must have a Lansky or Karnofsky performance status score of >= 50%, corresponding to ECOG categories of 0, 1, or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients < 16 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.
- Patients must not have received any prior chemotherapy, radiation therapy, immunotherapy, or bone marrow transplant.
- Hypertension must be well controlled (<+ 95th percentile for age and height if patients if patient is <= 17 years) on stable doses of medication. (See Appendices I and II for tables of blood pressure based on age and gender. If a patient falls between percentiles for height and age, then the average value should be considered the appropriate one.) If patient is > 17 years, adult normal values should be used (i.e., patients must have a SBP <= 150 mmHg and/or DBP <= 100 mmHg).
- All patients must have: Adequate bone marrow function, adequate renal function, urine protein screened by urine analysis, adequate liver function, adequate central nervous system function, and adequate coagulation (see section 3.2.8 for specific requirements).
- Exclusion criteria listed on page 33 of protocol.