WF-1801: Single Arm Pilot Study of Ramipril for Prevention of Radiation-Induced Cognitive Decline in Glioblastoma Patients Receiving Chemoradiotherapy

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ID: 314906
2026
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Abstract
Abstract Background To examine the feasibility of adding ramipril for prevention of cognitive decline to chemoradiation treatment of glioblastoma. Methods This prospective single arm study (WF-1801) coordinated by the Wake Forest NCI Community Oncology Research Program Research Base (UG1CA189824) assessed feasibility, tolerability, and potential efficacy of ramipril to prevent treatment-induced cognitive decline in patients with GBM. Inclusion criteria and chemoradiotherapeutic paradigms were mirrored to the standard arm of NRG/RTOG 0825, such that cognitive outcomes could be compared. All patients were treated with ramipril during chemoradiation and for 4 weeks after completion of radiotherapy (RT). Major outcomes were retention and the Clinical Trial Battery Composite (CTB COMP) score of the cognitive tests. Results were compared to the corresponding outcomes from NRG/RTOG 0825. Results 75 participants were accrued between 3/25/2019 and 11/14/23: median age was 63 years. The NRG/RTOG 0825 cohort was younger (median 57 years, P < .0001). Overall retention rate at 1-month post RT (defined as compliant with 75% of doses and completion of cognitive testing) was 48% (one-sided 95% CI: 38%-100%); 61% of patients completed > =75% of doses and 57% had a CTB COMP score through week 10. The median (range) change in the CTB COMP score at 1 month after RT completion was 0.01 (-82.6, 13.0) versus NRG/RTOG 0825 median of 0.10 (-48.2, 8.6); P = .49. Conclusions The ramipril intervention did not meet the prespecified feasibility endpoint, neither did the cognitive scores differ significantly from the NRG/RTOG 0925 control group. We expect other agents will be the focus of future cytoprotective trials.
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Authors Christina K. Cramer, Sydney Smith, Emily V. Dressler, Brandi Page, Jeffrey S Wefel, Stephen R. Rapp, Edward H. Ip, Stephanie L. Pugh, Ashley Sumrall, Roy E Strowd, Zachary Vaslow, Gena Volas-Redd, Kathryn E Weaver, Glenn J. Lesser, Michael D. Chan
Journal Neuro-Oncology Practice
Year 2026
DOI
10.1093/nop/npag047
URL
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