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

NCT06766266 | Recruiting Phase 1 DMC

• 1 other identifier: 2024-549-02
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Non-Muscle Invasive Bladder Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• Bone marrow suppression (Grade four)

  1. Absolute Neutrophil Count \< 0.5\*10\^9/L 2. Platelet \<25\*10\^9/L 3. leukocyte \<1.0\*10\^9/L

  4 weeks

Secondary Outcomes (5)

• Safety and adverse events

  2 months

• Objective remission rate (Arm A available)

  4 weeks

• Recurrence-free survival (Arm B available)

  3-6 months

• BLM Lactylation of tumor tissues

  4 weeks

• The levels of DNA double-strand break and homologous recombination repair in tumor tissues

  4 weeks

Study Arms (2)

Arm A: TURBT unresectable

EXPERIMENTAL

If the recurrent tumor can't be excised by TURBT, participants will be assigned to this arm. Participants in this arm will complete the neoadjuvant 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), and the therapeutic effect was evaluated by pelvic enhanced MRI and cystoscopy. Judged by two urologists with senior professional title, patients with complete response and partial response were treated with TURBT and intravesical therapy. Patients with stable disease or progressive disease received subsequent therapy at the investigator's discretion. Participants will visit the clinic once every 2 weeks for checkups and tests.

Drug: Irinotecan liposome II combination therapy regimen

Arm B: TURBT resectable

EXPERIMENTAL

If the recurrent tumor can be excised by TURBT, participants will be assigned to this arm (Arm B). Participants in this arm will complete TURBT with immediate intravesical instillation of epirubicin (50 mg) within 24 hours after surgery. During the induction phase (the first 1 month after surgery), participants will receive 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). In the next 6 months, participants will continue the intravesical instillation treatment with epirubicin (once a month, 50 mg). Participants will visit the clinic once every 2 weeks for checkups and tests in the first month, and once every 3 months after the first month.

Drug: Irinotecan liposome II combination therapy regimen

Interventions

Irinotecan liposome II combination therapy regimen DRUG

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.

Arm A: TURBT unresectable

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• First Affiliated Hospital of Chongqing Medical University: lead

Study Sites (1)

The First Affiliated Hospital of Chongqing Medica University

Chongqing, 400010, China

RECRUITING

Study Officials

• Xin Gou, Professor

  cymnk@163.com

  STUDY CHAIR

Central Study Contacts

Xin Gou, Professor

CONTACT

0086+13650518875; cymnk@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: It is a double cohort study, the two cohorts are incomparable. If the recurrent tumor can't be excised by transurethral resection of bladder tumor (TURBT), the participant will enter the A arm, and if the recurrent tumor can be excised by TURBT, the participant will enter the B arm.

Study Record Dates

• First Submitted: January 3, 2025
• First Posted: January 9, 2025
• Study Start: January 10, 2025
• Primary Completion: April 24, 2025
• Study Completion: December 24, 2025
• Last Updated: March 26, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: The IPD and supporting information will be available after 2026.6.1
• Access Criteria: Study protocal of the study is available from professor XinGou(email:cymnk@163.com)

Locations

CN (1)