A randomized phase III trial investigating platinum and taxane chemotherapy in metastatic castration-resistant prostate cancer (mCRPC) patients with alterations in DNA damage response (DDR) genes (OPTION-DDR) CCTG-PR-25 NCT06439225.

Abstract

TPS5143 Background: Outcomes for patients (pts) with mCRPC after androgen receptor pathway inhibitors (ARPI) remain poor. There are numerous treatment options, including single agent docetaxel, however overall survival (OS) after ARPI is between 12-19 months. Thus, management of mCRPC post-ARPI represents an area of unmet need. 25% of pts have alterations in DDR genes, which may be a biomarker for sensitivity to treatment with platinum agents. Carboplatin has been previously evaluated in smaller trials in pts with mCRPC and shows promise in patients with DDR gene alterations. PR-25 leverages standard of care testing for DDR genes to evaluate in a rigorous manner whether addition of carboplatin to docetaxel improves overall survival (OS) in pts with DDR gene alterations and mCRPC. Methods: PR-25 is a phase III randomized controlled trial led by the Canadian Cancer Trials Group comparing docetaxel to docetaxel and carboplatin in pts with DDR alterations. Pts must receive prior ARPI for mCRPC and demonstrate radiographic or PSA progression prior to enrollment. Qualifying DDR gene alterations include: BRCA1, BRCA2, ATM, ATR, BRIP1, BARD1, CDK12, CHEK1, CHEK2, ERCC2, FANCA, FANCC, FANCD2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, RAD54L. The primary endpoint is OS. Secondary endpoints include radiographic progression free survival (PCWG3 and RECIST 1.1), PSA response, time to next systemic therapy, patient reported quality of life and economic evaluation. Statistical design: The target accrual is 236 patients over 3.25 yrs with 2 year follow-up to detect a HR of 0.65 in OS, using a type 1 error rate of 5% (2 sided) and power of 80%. Conduct to Date: Study activation – October 2024. First patient enrolled - December 2024. Accrual to date: 10. Clinical trial information: NCT06439225 .