Bladder urothelial carcinoma
Conditions
Interventions
Experimental group:Tislelizumab with gemcitabine-cisplatin (GC)
Sponsors
Chinese PLA General Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Voluntary participation in this trial, able to provide a written informed consent form, and able to understand and agree to comply with the requirements and assessment schedule of this study; 2. Age between 18 and 75 years old on the date of signing the informed consent form; 3. Participants with residual lesions after TURBT surgery, with cT2-T4aN0M0 bladder urothelial carcinoma confirmed histologically and evaluated by imaging based on the 8th edition of the AJCC bladder cancer TNM staging system; for participants with mixed-type tumors, urothelial carcinoma must be the dominant type (at least 50%); 4. Must be determined by the investigator to be suitable for cisplatin-based treatment. Participants unsuitable for cisplatin chemotherapy must meet at least one of the following criteria: (1) ECOG performance status >1 or Karnofsky performance status of 60% to 70%; (2) Creatinine clearance rate below 60 ml/min; (3) Hearing loss >= Grade 2 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5; (4) Peripheral neuropathy >= Grade 2 according to NCI-CTCAE version 5; (5) Diagnosis of New York Heart Association Class III or higher heart failure; 5. As evaluated by the investigator, participants who need to undergo radical cystectomy or TURBT or partial cystectomy after neoadjuvant therapy and meet the surgical indications, and are willing to undergo the surgery; 6. Must provide a tumor tissue sample from TURBT, and also provide the relevant pathological report. Fresh surgical tissue or pathological slides can be sent for examination; 7. ECOG performance status 0 or 1; 8. Good organ function of the participant, measured by the following screening period laboratory test values obtained within =1.5×10^9/L; 2) Platelet count >=100×10^9/L; 3) Hemoglobin >=90g/L; (2) International Normalized Ratio (INR) or activated partial thromboplastin time =60 mL/min (Appendix 9); (4) Total serum bilirubin <=1.5×ULN (if Gilbert's syndrome or indirect bilirubin concentration indicates extrahepatic elevation, it should be <=3×ULN); (5) Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), and alkaline phosphatase <=2.5×ULN; (6) Pulmonary function indicates the ability to tolerate major abdominal surgery; 9. Unpregnant or fertile women must be willing to take effective contraceptive measures during the study and for at least 120 days after the last administration of tislelizumab or chemotherapy (whichever occurs later), and have a negative urine or serum pregnancy test result within 7 days before enrollment; 10. Unsterilized men must be willing to take effective contraceptive measures during the study and for at least 120 days after the last administration of tislelizumab or chemotherapy (whichever occurs later).
Exclusion criteria
Exclusion criteria: 1. Prior therapy targeting PD-1, PD-L1, PD-L2, or CTLA-4, or treatment with other antibodies or drugs specifically targeting T-cell co-stimulation or checkpoint pathways; 2. Received other approved systemic anticancer therapy or systemic immunomodulatory agents (including but not limited to interferon, interleukin-2, and tumor necrosis factor) within 28 days prior to enrollment; 3. Previous radiotherapy for bladder cancer; 4. Prior antitumor drug therapy, with the following exceptions: (1). For participants who have previously received systemic chemotherapy, a treatment-free interval of at least 12 months from the last treatment to the start of neoadjuvant therapy is required; (2). Intravesical chemotherapy or immunotherapy must have been completed at least 1 week prior to the start of the study's neoadjuvant therapy; 5. Major surgery or significant trauma within 28 days prior to enrollment (implantation of vascular access devices and TURBT are not considered major surgeries); 6. Severe chronic or active infection requiring systemic antibacterial, antifungal, or antiviral treatment within 14 days prior to enrollment (management of HBV infection follows the instructions in exclusion criterion #11); 7. Administration of live vaccines within 28 days prior to enrollment (seasonal injectable influenza vaccines are typically inactivated and are therefore permitted; intranasal vaccines are live and are not allowed); 8. Use of any Chinese herbal medicines or proprietary Chinese medicinal products for cancer control within 14 days prior to enrollment (see Appendix 4); 9. Active autoimmune disease requiring systemic treatment that, in the investigator’s judgment, may affect the study treatment (see Appendix 5); 10. Long-term use of high-dose corticosteroids or other immunosuppressants that, in the investigator’s judgment, may affect the study treatment; 11. History of abnormal potassium, sodium, or calcium levels, hypoalbuminemia, interstitial lung disease, non-infectious pneumonitis, or other uncontrolled systemic diseases (including diabetes, hypertension, cardiovascular disease [e.g., active cardiac disease within 6 months prior to enrollment, including severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, and ventricular arrhythmias requiring medication], etc.) that, in the investigator’s opinion, may affect the treatment; 12. Participants with untreated chronic hepatitis B (HBV DNA >=500 IU/mL [2500 copies/mL]) or hepatitis B virus (HBV) carriers are excluded. *Note: Inactive hepatitis B surface antigen (HBsAg) carriers or participants with stable active HBV infection (HBV DNA <500 IU/mL [2500 copies/mL]) after sustained antiviral therapy may be enrolled. HBV DNA testing is only required for participants who test positive for hepatitis B core antibody (anti-HBc); 13. Participants with active hepatitis C are excluded. Participants who test negative for HCV antibody during screening, or those who test positive for HCV antibody but negative for HCV RNA, may be enrolled. Only participants positive for HCV antibody require HCV RNA testing; 14. History of immunodeficiency (including a positive HIV test, other acquired or congenital immunodeficiency diseases) or allogeneic stem cell transplantation or organ transplantation; 15. Known allergy to monoclonal antibodies; 16. Known hypersensitivity to any study drug or excipient; 17. Toxicities (from any prior treatment) that have not resolved to baseline or stabilized, un
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| pathologic Complete Response (pCR);One-year bladder intact disease-free survival (BIDFS); | — |
Secondary
| Measure | Time frame |
|---|---|
| Pathological downstaging date;Event-free survival rate (EFS);Disease control rate (DCR);Overall survival rate (OS);Molecular profiling and analyses (including, but not limited to: PD-L1 expression, tumor mutational burden (TMB), TCGA molecular classification, investigations into the unique mechanism of action and Fc engineering of tislelizumab, and research on other predictive biomarkers);Safety; | — |
Countries
China
Contacts
Public ContactXu Zhang
Chinese PLA General Hospital
Outcome results
None listed