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

Официальное название

A Prospective, Randomized, Open-Label, Phase II Trial Comparing Sequential Intravesical Gemcitabine Plus Docetaxel With Sequential Intravesical Gemcitabine Plus Mitomycin C in Patients With BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Gemcitabin
  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.
• Препарат Docetaxel
  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.
• Препарат Mitomicin C
  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.

Первичные конечные точки

• 12-Month Event-Free Survival [Срок оценки: 12 months after randomization]

Вторичные конечные точки (5)

• Progression-Free Survival [Срок оценки: Up to 12 months]
• Cystectomy-Free Survival [Срок оценки: Up to 12 months]
• Treatment-Related Adverse Events [Срок оценки: Throughout study treatment and follow-up]
• Health-Related Quality of Life (EORTC QLQ-C30) [Срок оценки: Baseline through 12 months]
• Health-Related Quality of Life (EORTC QLQ-NMIBC24) [Срок оценки: Baseline through 12 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Россия · 1 центр

• N.N. Blokhin National Medical Research Center of Oncology — Moscow

Идентификаторы

NCT: NCT07747740 · NMIBC-GEMDOC-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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