WF-1801: Single-arm pilot study of ramipril for prevention of radiation-induced cognitive decline in glioblastoma patients receiving chemoradiotherapy.

BACKGROUND

To examine the feasibility of adding ramipril for prevention of cognitive decline to chemoradiation treatment of glioblastoma (GBM).

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

A total of 75 participants were accrued between March 25, 2019 and November 14, 2023: 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% (1-sided 95% CI: 38%-100%); 61% of patients completed more than 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.