Sequential Gemcitabine Plus Docetaxel Versus Gemcitabine Plus Mitomycin C for BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer

Phase 2RecruitingNCT07747740

Blokhin's Russian Cancer Research Center228 enrolled

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Interventions

GemcitabinDRUG

Intravesical gemcitabine 1 g dissolved in 50 mL of 0.9% sodium chloride. The solution is retained in the bladder for 90 minutes before drainage.

DocetaxelDRUG

Intravesical docetaxel 37.5 mg dissolved in 50 mL of 0.9% sodium chloride. The solution is retained in the bladder for 90 to 120 minutes following gemcitabine administration.

Mitomicin CDRUG

Intravesical mitomycin C 40 mg dissolved in 40 mL of 0.9% sodium chloride. The solution is retained in the bladder for 90 minutes following gemcitabine administration.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age ≥18 years. 2. Histologically confirmed BCG-unresponsive non-muscle-invasive urothelial bladder cancer (NMIBC). 3. Complete transurethral resection of bladder tumor (TURBT) before study treatment. 4. Intermediate- or high-risk NMIBC according to current clinical guidelines. 5. Candidate for intravesical chemotherapy. 6. ECOG performance status 0-2. 7. Adequate hematologic, renal, and hepatic function. 8. Written informed consent. Exclusion Criteria: 1. Muscle-invasive (≥T2), locally advanced, or metastatic urothelial carcinoma. 2. Upper urinary tract urothelial carcinoma requiring treatment. 3. Previous hypersensitivity to gemcitabine, docetaxel, mitomycin C, or formulation components. 4. Active uncontrolled urinary tract infection. 5. Pregnancy or breastfeeding. 6. Concurrent participation in another interventional clinical trial. 7. Any serious uncontrolled medical condition that, in the investigator's opinion, would interfere with study participation or interpretation of results.

Outcomes

Primary Outcomes

12-Month Event-Free Survival

Event-free survival is defined as the time from randomization to the first occurrence of histologically confirmed recurrence, disease progression to muscle-invasive bladder cancer, radical cystectomy, distant metastasis, or death from any cause.

Time frame: 12 months after randomization

Secondary Outcomes

Progression-Free Survival

Time from randomization to progression to muscle-invasive or metastatic urothelial carcinoma.

Time frame: Up to 12 months

Cystectomy-Free Survival

Time from randomization to radical cystectomy for bladder cancer.

Time frame: Up to 12 months

Treatment-Related Adverse Events

Incidence and severity of adverse events graded according to CTCAE.

Time frame: Throughout study treatment and follow-up

Health-Related Quality of Life (EORTC QLQ-C30)

Change from baseline in EORTC QLQ-C30 scores.

Time frame: Baseline through 12 months

Health-Related Quality of Life (EORTC QLQ-NMIBC24)

Change from baseline in EORTC QLQ-NMIBC24 scores.