An example of drug repurposing: ebastine in combination with docetaxel as a treatment for metastatic castration-resistant prostate cancer-the EXUROC prostate study, a clinical trial protocol.

BACKGROUND: This clinical trial investigates the addition of a repurposed drug, the cationic amphiphilic drug (CAD) ebastine, to docetaxel in metastatic castration resistant prostate cancer (mCRPC). Preclinical data have shown that chemotherapy-resistant prostate cancer cells can be re-sensitized and that combining CAD with docetaxel significantly inhibits tumor growth in xenograft mouse models of docetaxel-resistant mCRPC. The primary objective of this study is to evaluate the impact of ebastine plus docetaxel versus docetaxel alone for mCRPC, measured as Bis(monoacylglycero)phosphate (BMP) and lysophospholipids in urine and blood. Secondary endpoints are prostate-specific antigen (PSA) and radiologic progression-free survival. METHODS: This randomized, open-label, phase ll trial will include 30 patients with disease progression after prior therapy for mCRPC, in a 2:1 ratio favoring the intervention arm. Inclusion criteria are metastatic adenocarcinoma/poorly differentiated carcinoma of the prostate, serum testosterone levels ≤ 50 ng/dL., and that patients are planned for docetaxel treatment. DISCUSSION: The trial was initiated on 1 June 2024 and is currently recruiting participants. Results are expected to be available by Q4 2027. This phase II study aims to evaluate the clinical effectiveness of CADs, with a specific focus on biomarkers such as BMP and lysophospholipids. This biomarker-driven approach offers a unique opportunity to gain insight into the biological effects of the combination treatment, particularly its impact on lysosomal lipid metabolism. If the biological rationale is confirmed, the study will proceed to a phase II/III large-scale randomized trial. TRIAL REGISTRATION: The trial is registered on ClinicalTrials.gov as NCT06480110.