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
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 that will employ a randomized â??pick the winnerâ?? 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 standard treatment arm (temozolomide during chemoradiotherapy); and a randomized phase III part where patients will be randomized to either the chosen experimental arm or the temozolomide arm for a formal efficacy (EFS) comparison.
Age greater than / equal to 3 years and less than 22 years at the time of enrollment Newly diagnosed non-metastatic high-grade glioma. Primary brainstem tumor, oligodendroglioma, and oligoastrocytoma ineligible. Patients must have histologic verification of diagnosis. M+ disease ineligible. No prior therapy allowed on this study. Adequate organ function required.
All patients must begin therapy within 31 days after definitive surgery. Radiation will be given in standard fractions (total dose 59.4 Gy) over 6 weeks. During radiation, patients will receive chemotherapy per one of the three arms described above. All patients will begin Maintenance therapy with bevacizumab and temozolomide commencing 4 weeks after completion of RT for up to a total of 12 cycles.
06/18/2013 04:02 AM