Abstract 2513: Factors influencing participant attrition in Phase 0 hybrid clinical trials for patients with high-grade glioma

Abstract Background: Phase 0 hybrid trial designs administer a subtherapeutic experimental agent pre-surgically and then use predetermined pharmacokinetic (PK) and/or pharmacodynamic (PD) thresholds to qualify patients for follow-on therapeutic dosing. While such protocols are rare, they are increasingly prevalent within neuro-oncology, necessitating a better understanding of factors influencing participation. Here, we investigate participant enrollment in Phase 0 hybrid trials for high-grade glioma patients at a single center. Methods: This retrospective study examined characteristics of high-grade glioma patients enrolled in Phase 0 hybrid clinical trials at the Ivy Brain Tumor Center. Clinical, pathological and demographic data, as well as PK/PD profiles, were analyzed and related to participant enrollment and attrition. Results: A total of 284 newly-diagnosed and recurrent high-grade glioma patients were analyzed and 276 (97.2%) participants completed the Phase 0 component of their study. Of these, 176 (63.8%) Phase 0 participant tumors did not meet criteria for therapeutic dosing, including 63 (35.8%) due to histological diagnosis, 62 (35.2%) due to PK/PD results, 39 (22.2%) due to clinical status decline, 7 (4.0%) due to patients’ decision to not proceed, and 5 (2.8%) for unknown reasons. Six (2.1%) participants did not complete Phase 0 and 2 (0.7%) participants were screen failures. Conclusions: In the upfront and recurrent settings, tumor histopathology and drug PK/PD performance are the principal determinants of participant suitability for the therapeutic dosing component of a Phase 0 hybrid study. In this single-center analysis, the graduation rate from Phase 0 to therapeutic dosing was 36.2%. This retrospective study, the largest to date in high-grade glioma patients, highlights participant- and protocol design-related features that will help refine future Phase 0 hybrid protocols in neuro-oncology. Citation Format: Jocelyn L. Harmon, Amy Hong, Artak Tovmasyan, An-Chi Tien, Kristin Hendrickson, Jennifer Eschbacher, Wonsuk Yoo, Igor Barani, William Kennedy, Zaman Mirzadeh, Yoshie Umemura, Shwetal Mehta, Nader Sanai. Factors influencing participant attrition in Phase 0 hybrid clinical trials for patients with high-grade glioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2513.