G-DISCO: Gemcitabine-docetaxel intravesical instillation synchronous co-administration—A phase I study.

TPS897 Background: Treatment options are notably limited for BCG-unresponsive high-risk non-muscle invasive bladder cancer (HR-NMIBC), often involving intravesical chemotherapy or radical cystectomy. If a patient is unsuitable for cystectomy, or they decline, guidelines suggest intravesical chemotherapy utilizing a combination of gemcitabine and docetaxel 1,2 . Traditionally, these drugs have been administered sequentially with no previous studies investigating synchronous intravesical instillation of gemcitabine-docetaxel. Synchronous treatment has potential resource and time-utlization advantages but has not been formally studied. Methods: G-DISCO (ANZUP 2403, ACTRN12624001188527p) is a single-arm, Phase I study designed to assess the feasibility, safety, and tolerability of synchronous intravesical instillation of gemcitabine and docetaxel. The study has Ethics approval and is currently recruiting patients with fully resected HR-NMIBC that is unresponsive or unsuitable for intravesical BCG therapy and where the patient is unwilling or unable to undergo radical cystectomy. Participants will receive synchronous intravesical administration of gemcitabine (1 g) and docetaxel (37.5 mg), both agents constituted together in 50 mL of saline. The combined solution will be administered via urinary catheter with a recommended minimum dwell time of 60 minutes, aiming for an optimal dwell time of 90 minutes. This intravesical treatment will be repeated weekly for six weeks. This study will enroll 15 patients and has a two-year recruitment strategy expected to finish recruiting in 2026. Feasibility of synchronous intravesical administration of gemcitabine and docetaxel will be assessed by the completion rates of the planned six-week course. Safety will be monitored through the recording of adverse events and tolerability will be evaluated using AUA-SI / IPSS, and NMIBC-SI. Secondary endpoints include; recurrence rates at three months post-treatment, effects of regimen on carbon footprint, pharmacokinetic impacts of combined administration, and tissue translational end-points. If successful, G-DISCO could establish a new standard for administering intravesical gemcitabine-docetaxel, offering several potential advantages including shortened treatment time for patients, improved unit time-efficiency and resource savings for healthcare facilities, and reduced exposure for staff handling these cytotoxic agents. References: 1. Holzbeierlein JM et al. Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer: AUA/SUO Guideline: 2024 Amendment. J Urol. 2024;211(4):533-8. 2. Bladder intravesical DOCEtaxel and gemcitabine 2023 [cited 2024 09 Jul]. Available from: https://www.eviq.org.au/medical-oncology/urogenital/bladder-and-urothelial/4320-bladder-intravesical-docetaxel-and-gemcitabin Clinical trial information: ACTRN12624001188527p.