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.
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
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
Single group
Rutin
DrugRutin 40 mg tid. Treatment will be given for 2 cycles (21 days per cycle)
Gemcitabine, Cisplatin
DrugCisplatin 100 mg/m² D2 q3w, and Gemcitabine 1000 mg/m² D1, D8 q3w. Treatment will be given for 2 cycles (21 days per cycle)
Tislelizumab
DrugTislelizumab 200 mg D1 q3w Treatment will be given for 2 cycles (21 days per cycle)
Tumor microenvironment
Immune microenvironment and epigenetic alterations in bladder tumors, including immune cell components.
Safety and adverse events
The description of adverse events will be coded according to MedDRA terminology and graded according to NCI-CTCAE v5.0.
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
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