Overview
This prospective, randomized, open-label, phase II clinical trial compares two sequential intravesical chemotherapy regimens in patients with bacillus Calmette-Guérin (BCG)-unresponsive high-grade non-muscle-invasive bladder cancer (NMIBC) following complete transurethral resection of bladder tumor (TURBT). Participants are randomized in a 1:1 ratio to receive sequential intravesical gemcitabine plus docetaxel or sequential intravesical gemcitabine plus mitomycin C. The primary objective is to compare 12-month event-free survival between treatment groups. Secondary objectives include evaluation of cystectomy-free survival, progression-free survival, treatment safety, tolerability, and patient-reported quality of life.
Description
High-grade BCG-unresponsive non-muscle-invasive bladder cancer remains a major therapeutic challenge. Radical cystectomy is considered the standard treatment; however, many patients are unwilling or medically unfit to undergo surgery. Sequential intravesical chemotherapy has emerged as a bladder-preserving treatment strategy with encouraging oncological outcomes.
This prospective, randomized, open-label, single-center phase II trial is designed to compare the efficacy and safety of two sequential intravesical chemotherapy regimens following complete TURBT.
Eligible patients with histologically confirmed BCG-unresponsive high-grade NMIBC will be randomized in a 1:1 ratio to receive either sequential intravesical gemcitabine followed by docetaxel or sequential intravesical gemcitabine followed by mitomycin C.
Both treatment regimens consist of a six-week induction course followed by monthly maintenance instillations for twelve months according to the study protocol. Clinical follow-up includes cystoscopy, urine cytology, pelvic ultrasonography, adverse event assessment according to CTCAE criteria, and quality-of-life evaluation using the EORTC QLQ-C30 and EORTC QLQ-NMIBC24 questionnaires.
The primary endpoint is 12-month event-free survival. Secondary endpoints include cystectomy-free survival, progression-free survival, safety, tolerability, and comparative efficacy of both treatment strategies.
A total of 228 participants will be enrolled. Statistical analyses will be performed according to the intention-to-treat principle using Kaplan-Meier survival analysis, log-rank testing, and Cox proportional hazards regression.
Eligibility
Inclusion Criteria:
- Age ≥18 years.
- Histologically confirmed BCG-unresponsive non-muscle-invasive urothelial bladder cancer (NMIBC).
- Complete transurethral resection of bladder tumor (TURBT) before study treatment.
- Intermediate- or high-risk NMIBC according to current clinical guidelines.
- Candidate for intravesical chemotherapy.
- ECOG performance status 0-2.
- Adequate hematologic, renal, and hepatic function.
- Written informed consent.
Exclusion Criteria:
- Muscle-invasive (≥T2), locally advanced, or metastatic urothelial carcinoma.
- Upper urinary tract urothelial carcinoma requiring treatment.
- Previous hypersensitivity to gemcitabine, docetaxel, mitomycin C, or formulation components.
- Active uncontrolled urinary tract infection.
- Pregnancy or breastfeeding.
- Concurrent participation in another interventional clinical trial.
- Any serious uncontrolled medical condition that, in the investigator's opinion, would interfere with study participation or interpretation of results.
