Irinotecan Liposomes Combined with Epirubicin in Recurrent Non-muscle Invasive Bladder Urothelium Carcinoma After Anthracyclines Treatment

Официальное название

A Phase I, Open-Label Clinical Study of Irinotecan Liposomes Combined with Epirubicin in Recurrent Non-Muscle Invasive Bladder Urothelium Carcinoma After Anthracyclines Treatment

Обзор

The goal of this clinical trial is to learn the dose-limiting toxicity of the new combined treatment with irinotecan liposomes (intravenous injection) and epirubicin (intravesical instillation) in anthracyclines treatment-failed non-muscle invasive bladder cancer adults. It will also learn if the combined treatment works to treat these patients. Additionally, the safety and biological mechanisms of the combined treatment will also be explored. The main questions it aims to answer are: * Does the combined treatment of irinotecan liposomes and epirubicin reverse anthracyclines resistance of participants? * What medical problems do participants have after taking the combined treatment of irinotecan liposomes and epirubicin? * What biological mechanisms underlie the effect of irinotecan liposomes on anthracyclines resistance? Participants will be classified into Arm A and Arm B. * Arm A: Participants will receive an intravenous injection of irinotecan liposomes once every two weeks for one month, along with intravesical instillation of epirubicin once a week for one month. Patients will be evaluated by two professional urologists; those with a complete response or partial response will undergo transurethral resection of bladder tumor (TURBT) and intravesical therapy. Patients with stable or progressive disease will receive subsequent treatment at the investigator's discretion. Participants are required to visit the hospital for physical examination every two weeks. * Arm B: In the first month after TURBT surgery, participants will receive intravenous injection of irinotecan liposomes once every two weeks for one month, and intravesical instillation of epirubicin once a week for one month, followed by once a month for six months. Participants are required to visit the clinic for physical examination once every two weeks in the first month, and once every three months after that. * Keep a diary of their symptoms during the study period.

Вмешательства

• Препарат Irinotecan liposome II combination therapy regimen
  In the A arm, the combined treatment with irinotecan liposome (intravenous injection, once every two weeks for 1 month, dose increasing regimen: 37.6 mg/m2 and 56.5mg/m2) and epirubicin (intravesical instillation, once a week for 1 month, 50 mg) is in the neoadjuvant therapy phase before TURBT surgery.
• Препарат Irinotecan liposome II combination therapy regimen
  In the B arm, the combined therapy with irinotecan liposome (intravenous injection, once every two weeks for 1 month, dose increasing regimen: 37.6 mg/m2 and 56.5mg/m2 ) and epirubicin (intravesical instillation, once a week for 1 month, 50 mg) is in the induction phase after TURBT surgery.

Первичные конечные точки

• Bone marrow suppression (Grade four) [Срок оценки: 4 weeks]

Вторичные конечные точки (5)

• Safety and adverse events [Срок оценки: 2 months]
• Objective remission rate (Arm A available) [Срок оценки: 4 weeks]
• Recurrence-free survival (Arm B available) [Срок оценки: 3-6 months]
• BLM Lactylation of tumor tissues [Срок оценки: 4 weeks]
• The levels of DNA double-strand break and homologous recombination repair in tumor tissues [Срок оценки: 4 weeks]

Критерии участия

Критерии включения

• cTa-cT1N0M0 patients with non-muscle invasive urothelial carcinoma
• Tumor recurrence occurred after anthracyclines treatment
• Systemic chemotherapy had not been used
• Tumor is measurable according to New response evaluation criteria in solid tumours: Revised RECIST guideline
• ECOG (ZPS, 5-point scale) 0-1

Критерии исключения

• Age less than 18 years
• Patients with severe cardiac, cerebral, hepatic, or renal disease
• Severely malnourished patients
• Patients with mental illness and those without insight and unable to express exactly
• Combined with malignant tumors of other organs
• Systemic infectious diseases

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The First Affiliated Hospital of Chongqing Medica University — Чунцин

Публикации

• Li X, Zhang C, Mei Y, Zhong W, Fan W, Liu L, Feng Z, Bai X, Liu C, Xiao M, He W, Lin T, Gou X. Irinotecan alleviates chemoresistance to anthracyclines through the inhibition of AARS1-mediated BLM lactylation and homologous recombination repair. Signal Transduct Target Ther. 2025 Jul 10;10(1):214. doi: 10.1038/s41392-025-02302-y. PMID 40634292

Идентификаторы

NCT: NCT06766266 · 2024-549-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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