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

Phase 1

Recruiting

• Conditions: Muscle Invasive Bladder Cancer
• Interventions: Drug: Rutin; Drug: Gemcitabine, Cisplatin; Drug: Tislelizumab

• Registration Number: NCT06916494
• Lead Sponsor: First Affiliated Hospital of Chongqing Medical University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-02
• Study First Submitted: 2025-04-01
• Study First Submitted QC: 2025-04-01
• Study First Posted: 2025-04-08
• Last Update Submitted: 2025-04-08
• Last Update Posted: 2025-04-10
• Study Start: 2025-05-01
• Primary Completion: 2026-01-20
• Study Completion: 2026-01-20

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 10

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Rutin combined with Tislelizumab and GC	Rutin	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.
Rutin combined with Tislelizumab and GC	Tislelizumab	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.
Rutin combined with Tislelizumab and GC	Gemcitabine, Cisplatin	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Safety and adverse events	From enrollment to the end of treatment at 6 weeks	The description of adverse events will be coded according to MedDRA terminology and graded according to NCI-CTCAE v5.0.
Objective remission rate	From enrollment to the end of treatment at 6 weeks	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

Trial Locations

Locations (1)

First Affiliated Hospital of Chongqing Medical University; 🇨🇳 ChongQing, Chongqing, China