Tr-14 * a Feasibility and Randomized Phase Ii Study of Vorinostat, Bevacizumab, or Temozolomide During Radiation Followed by Maintenance Chemotherapy in Newly-diagnosed Pediatric High-grade Glioma: Children's Oncology Group Study Acns0822
Year: 2015
Type: article
Study design: Clinical Trial
Abstract: BACKGROUND: High-grade gliomas (HGGs) in children consistently demonstrate poor outcome despite multi-modal therapy. ACNS0822 was a feasibility and phase II trial in newly-diagnosed pediatric HGG. METHODS: In the feasibility study, patients received vorinostat 230 mg/m2/dose daily during radiation therapy (RT). In the phase II study, patients were randomized to one of three radiosensitizing agents during RT: Arm A [vorinostat 230 mg/m2/dose on Days 1-5 weekly], Arm B [temozolomide (TMZ) 90 mg/m2/dose daily], and Arm C [bevacizumab (BEV) 10 mg/kg/dose on Days 22 and 36]. All patients received BEV (10 mg/kg/dose every 2 weeks) + TMZ (200 mg/m2/dose on Days 1-5 q 28 days) for maintenance therapy × 12 cycles. The primary objectives were to determine 1) the feasibility of administering vorinostat during RT and 2) the 1-year event-free survival (EFS) of vorinostat or BEV with RT versus TMZ with RT as the historical control followed by maintenance chemotherapy. RESULTS: Six eligible patients were enrolled on the feasibility study; none experienced a dose limiting toxicity. The 95 patients enrolled (92 eligible) on the phase II study, were randomized to Arm A (vorinostat, n = 31), Arm B (TMZ, n = 29), and Arm C (BEV, n = 32). One-year EFS for Arms A, B, and C were 36.1 ± 10.4%, 54.8± 10.2%, 38.5 ± 10.1%, respectively. All chemoradiotherapy arms, and the maintenance arm were well-tolerated. The most common grade 3/4 toxicities in maintenance therapy included thrombocytopenia (9.6%), neutropenia (7%), and leukopenia (3.6%). Intracranial hemorrhage possibly attributable to BEV was reported in 2 patients in maintenance cycles 2 [grade 3] and 7 [grade 2]. There were no therapy-related deaths. CONCLUSION: Vorinostat (230 mg/m2/dose weekly) was tolerable during RT, as was maintenance therapy with BEV + TMZ. However, neither vorinostat, nor BEV proved superior to TMZ as a radiosensitizer in pediatric HGG.
Source: Neuro-Oncology
Authors: L. M. Hoffman, J. Geller, J. Leach, D. Boue, R. Drissi, L. Chen, M. Krailo, A. P. Panandiker, L. Chow, D. Haas-Kogan, S. Jogal, M. Nelson, R. Jakacki, M. Kieran, K. Cohen, I. Pollack, A. Gajjar, M. Fouladi
Institutions: Cincinnati Children's Hospital Medical Center, Dayton Children's Hospital, Children's Oncology Group, St. Jude Children's Research Hospital, University of California, San Francisco, Children's Hospital Los Angeles, Children's Hospital of Pittsburgh, Dana-Farber Cancer Institute, Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2146357043