Pilot Study on Rutin Combined With Tislelizumab and GC (Gemcitabine and Cisplatin) as Neoadjuvant Therapy for Platinum-refractory Muscle-invasive Bladder Cancer

A Single-Arm, Open-Label, Multicenter Pilot Study：Rutin Combined With Tislelizumab and GC (Gemcitabine and Cisplatin) for Platinum-refractory Muscle-Invasive Bladder Cancer

This trial aims to evaluate the efficacy, safety, and biological mechanisms of rutin combined with tislelizumab and GC(Gemcitabine and Cisplatin) in platinum-refractory muscle-invasive bladder cancer patients. Key research questions include:

1. Whether rutin regulates epigenetic mechanisms in tumor cells from platinum-refractory bladder cancer patients and modulates the tumor immune microenvironment.
2. Evaluating the safety and adverse events of the combination treatment in platinum-refractory bladder cancer patients.
3. Assessing the disease control rate in platinum-refractory bladder cancer patients receiving this therapy.

Patients with MIBC who exhibit no response (stable disease or progressive disease) after two cycles of neoadjuvant GC chemotherapy will receive two cycles of rutin combined with tislelizumab and GC. Safety and adverse events will be assessed after each cycle of combinational treatment. Therapeutic response will be evaluated by contrast-enhanced MRI, and surgical decisions (transurethral resection, partial cystectomy, or radical cystectomy) will be made by two senior urologists. Epigenetic alterations and the changes in immune microenvironment will be analyzed post-treatment.

Study Overview

• Status: Recruiting
• Conditions: Muscle Invasive Bladder Cancer
• Intervention / Treatment: Drug: Rutin; Drug: Gemcitabine, Cisplatin; Drug: Tislelizumab

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Xin Gou, Professor; Phone Number: 0086+13650518875; Email: cymnk@163.com

Study Locations

• China
  • Chongqing
    • ChongQing, Chongqing, China
      • Recruiting
      • First Affiliated Hospital of Chongqing Medical University
      • Contact: Xinyuan Li, Attending Physician; Phone Number: 13650518875; Email: lixinyuan@sibcb.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with cT2-cT4N0M0 muscle-invasive bladder cancer (MIBC)
• No response after 2 cycles of GC neoadjuvant chemotherapy
• No prior use of systemic immunotherapy or target therapy
• Tumor is measurable according to New response evaluation criteria in solid tumours: Revised RECIST guideline
• ECOG (ZPS, 5-point scale) 0-1

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Rutin combined with Tislelizumab and GC; Patients with MIBC who exhibit no response (stable disease or progressive disease) after two cycles of neoadjuvant GC chemotherapy (Cisplatin 100 mg/m² D2 q3w and Gemcitabine 1000 mg/m² D1, D8 q3w) will receive two cycles of rutin (40 mg tid.) combined with tislelizumab (200 mg D1 q3w) and GC (Cisplatin 100 mg/m² D2 q3w and Gemcitabine 1000 mg/m² D1, D8 q3w). Safety and adversed events will be assessed after every cycle of combinational treatment. Therapeutic response will be evaluated by contrast-enhanced MRI, and surgical decisions (transurethral resection, partial cystectomy, or radical cystectomy) will be made by two senior urologists. Epigenetic alterations and changes in the immune microenvironment will be analyzed post-treatment.

Drug: Rutin; Rutin 40 mg tid. Treatment will be given for 2 cycles (21 days per cycle); Drug: Gemcitabine, Cisplatin; Cisplatin 100 mg/m² D2 q3w, and Gemcitabine 1000 mg/m² D1, D8 q3w. Treatment will be given for 2 cycles (21 days per cycle); Drug: Tislelizumab; Tislelizumab 200 mg D1 q3w Treatment will be given for 2 cycles (21 days per cycle)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor microenvironment	Immune microenvironment and epigenetic alterations in bladder tumors, including immune cell components.	From enrollment to the end of treatment at 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and adverse events	The description of adverse events will be coded according to MedDRA terminology and graded according to NCI-CTCAE v5.0.	From enrollment to the end of treatment at 6 weeks
Objective remission rate	The proportion of patients with complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) after treatment was calculated according to established response evaluation criteria (Response Evaluation Criteria in Solid Tumors [RECIST], version 1.1). Definitions: CR (Complete Response): Disappearance of all target lesions with no new lesions. PR (Partial Response): ≥30% decrease in the sum of diameters of target lesions. SD (Stable Disease): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD (Progressive Disease): ≥20% increase in the sum of diameters of target lesions and/or appearance of new lesions	From enrollment to the end of treatment at 6 weeks

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Chongqing Medical University
• Investigators: Study Chair: Xin Gou, Professor, The First Affiliated Hospital of Chongqing Medica University

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2025
• Primary Completion (Estimated): January 20, 2026
• Study Completion (Estimated): January 20, 2026

Study Registration Dates

• First Submitted: April 1, 2025
• First Submitted That Met QC Criteria: April 1, 2025
• First Posted (Actual): April 8, 2025

Study Record Updates

• Last Update Posted (Actual): April 10, 2025
• Last Update Submitted That Met QC Criteria: April 8, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urologic Neoplasms; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Gemcitabine; Tislelizumab
• Other Study ID Numbers: ZZ2025-070-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The study outcomes and follow-up information will be available after paper publication.
• IPD Sharing Time Frame: The IPD and supporting information will be available after 2027.12.31
• IPD Sharing Access Criteria: Study protocal of the study is available from professor Xin Gou (email:cymnk@163.com)
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No