Phase II study of everolimus for recurrent or progressive pediatric ependymoma

• Published in: Neuro-oncology advances Vol. 5; no. 1; p. vdad011
• Main Authors: Bowers, Daniel C, Rajaram, Veena, Karajannis, Matthias A, Gardner, Sharon L, Su, Jack Meng-Fen, Baxter, Patricia, Partap, Sonia, Klesse, Laura J
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.01.2023
• Subjects: Clinical Investigations; ependymoma; mTOR pathway; everolimus; clinical trials
• ISSN: 2632-2498; 2632-2498
• DOI: 10.1093/noajnl/vdad011

Abstract Background Preclinical studies have suggested that mTOR pathway signaling may be a potential therapeutic target for childhood ependymoma. Methods A phase II clinical trial (ClinicalTrials.gov identifier: NCT02155920) of single-agent everolimus was performed to test the hypothesis that mTOR pathway inhibition would result in tumor responses for children with recurrent and/or progressive ependymomas. Results Eleven subjects [sex: 4 females (36.4%); median age: 8 years (range: 2-15 years); race: 9 white; prior therapies: median 6 (range: 3-9)] were enrolled on the study. Ten primary tumors were located in the posterior fossa and one primary tumor was located in the spinal cord. Eight of 9 tumors were PF-A subtype epenydmomas. All subjects were treated with oral everolimus 4.5 mg/m2/day (each cycle = 28 days) that was titrated to achieve serum trough levels of 5-15 ng/ml. Overall, everolimus was well tolerated; except for a single event of grade 3 pneumonia, all adverse events were grade 1-2. No objective tumor responses were observed. Participating subjects experienced tumor progression and discontinued therapy after a median of 2 cycles of therapy (1 cycle = 2; 2 cycles = 6; 3, 4, and 8 cycles = 1 each). Conclusions Everolimus does not appear to have activity for children with recurrent or progressive PF-A ependymoma.