Bladder cancer
Conditions
Interventions
Control group:1. Induction therapy phase: Toripalimab, 3 mg/kg, every 2 weeks
Vedicitumab, 2 mg/kg, every 2 weeks
2. Bladder preservation phase:
(1) Intensified therapy period: Toripalimab, 3 mg/kg, every 2 weeks
(2) Maintenance therapy period: Toripalimab 240 mg, every 3 weeks, for a total of 8 cycles.
Experimental group:1. Induction therapy phase: Clostridium butyricum tablets, 80mg bid
Toripalimab, 3mg/kg, q2w
Vedolizumab, 2mg/kg, q2w
2. Bladder preservation phase:
(1) Intensified therapy period: Clostridium butyricum tablets, 80mg bid
(2) Maintenance therapy period: Toripalimab 240mg, q3w
Clostridium butyricum tablets, 80mg bid, taken orally for 3 consecutive weeks, then stopped for 3 weeks.
Sponsors
Sun Yat-sen Memorial Hospital,Sun Yat-sen University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Voluntarily participate in this trial, able to sign the written informed consent form, and able to understand and agree to comply with the requirements and assessment schedule of this study; 2. Male or female aged 18 years or older on the day of signing the informed consent form; 3. Patients with residual lesions after TURBT surgery, diagnosed with cT2-3N0M0 bladder urothelial carcinoma based on the AJCC 8th edition bladder cancer TNM staging, histological confirmation, and imaging evaluation; for patients with mixed-type tumors, urothelial carcinoma must be predominant (>50%) and there must be pathological evidence of inherent muscle layer invasion; 4. Quantitative mass spectrometry detection of serum butyrate level =1; 7. Patient is not suitable for cisplatin-based therapy, meeting at least one of the following criteria: ECOG performance status >1 or Karnofsky performance status 60%–70%; creatinine clearance = grade 2 according to NCI-CTCAE v5.0; peripheral neuropathy >= grade 2 according to NCI-CTCAE v5.0; New York Heart Association Class III or higher heart failure. 8. ECOG performance status 0-2; 9. The patient has good organ function, assessed by the following screening laboratory values (obtained within 14 days prior to enrollment). (1) During the screening of the following items, the patient must not have used growth factor support within 14 days before sample collection: 1) Absolute neutrophil count >=1.5×10^9/L; 2) Platelets >=100×10^9/L; 3) Hemoglobin >=90 g/L; (2) International normalized ratio or activated partial thromboplastin time =1.5 times the upper limit of normal (ULN); (3) Calculated creatinine clearance >=30 mL/min; (4) Total serum bilirubin <=1.5×ULN (if Gilbert syndrome or indirect bilirubin elevation is of extrahepatic origin, it should be <=3×ULN); (5) AST, ALT, and alkaline phosphatase <=2.5×ULN; 10. Female subjects should be surgically sterile, postmenopausal, or agree to use at least one medically accepted method of contraception (e.g., intrauterine device, contraceptive pills, or condoms) during the study treatment and for 6 months after the end of the study treatment. A blood pregnancy test within 7 days prior to study enrollment must be negative. False positive results can be excluded by the investigator before enrollment. Male subjects must agree to use at least one medically accepted method of contraception during the study treatment and for 6 months after the end of the study treatment; 11. Willing and able to comply with study and follow-up procedures.
Exclusion criteria
Exclusion criteria: 1. Previously received therapy targeting PD-1, PD-L1, PD-L2, CTLA4, or HER2, or other antibodies or drugs specifically targeting T cell co-stimulation or checkpoint pathways; 2. History of allergic reactions to microbiota preparations; 3. Received other approved systemic anticancer therapy or systemic immunomodulators (including but not limited to interferons, interleukin-2, and tumor necrosis factor) within 28 days prior to enrollment; 4. Previously received radiotherapy for bladder cancer; 5. Previously received drug treatment for tumors, except for the following: (1) For patients who have previously received systemic chemotherapy, an untreated interval of at least 3 months from the end of the last treatment to the start of induction drug therapy; (2) Local intravesical chemotherapy or immunotherapy (including BCG therapy) must be completed at least 1 week before the start of the study neoadjuvant therapy; 6. Underwent major surgery or experienced significant trauma within 28 days prior to enrollment (placement of vascular access devices and TURBT are not considered major surgery); 7. Severe chronic or active infection requiring systemic antibacterial, antifungal, or antiviral treatment within 14 days prior to enrollment. 8. Live vaccine vaccination within 28 days prior to enrollment (seasonal influenza vaccines are usually inactivated vaccines, so they are allowed.) Intranasal vaccines are live vaccines, so they are not allowed); 9. Active autoimmune disease requiring systemic treatment, which is assessed by the investigator to have an impact on the study treatment; 10. Long-term use of hormones or other immunosuppressive drugs, which are assessed by the investigator to have an impact on the study treatment; 11. History of potassium, sodium, calcium abnormalities or hypoalbuminemia, interstitial lung disease, non-infectious pneumonitis or other uncontrolled systemic diseases that may affect treatment as determined by the investigator, including diabetes, hypertension, cardiovascular disease (such as active cardiac disease within 6 months before enrollment, including: severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, ventricular arrhythmia requiring medication, etc.), etc. 12. Subjects with untreated chronic hepatitis B or hepatitis B virus (HBV) carriers with HBV DNA>=500IU/mL (2500 copies/mL) are not allowed to enter the study. Note: Patients who are inactive hepatitis B surface antigen carriers or who are stable on continuous antiviral therapy with active HBV infection (HBV DNA< 500 IU/mL [2500 copies/mL]) can be enrolled. HBV DNA testing is performed only in patients who are positive for antibodies to the hepatitis B core antigen; 13. Patients with active hepatitis C are not allowed to be enrolled. Patients with negative HCV antibody test during the screening period, or patients with negative HCV RNA test after positive HCV antibody test can be enrolled. Only patients with positive HCV antibody test need HCV RNA testing; 14. History of immunodeficiency (including positive HIV test for human immunodeficiency virus, other acquired and congenital immunodeficiency diseases) or allogeneic stem cell transplantation or organ transplantation; 15. Known allergy to other monoclonal antibodies; 16. Known allergy to any of the study drugs or excipients; 17. Patients whose toxic side effects (due to any treatment) have not returned to baseline or stable levels, unless the investigator does not b
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Bladder-intact event-free survival (BI-EFS); | — |
Secondary
| Measure | Time frame |
|---|---|
| Clinical complete response rate (cCR rate);metastasis-free survival (MFS);overall survival (OS);Quality of life (QoL); | — |
Countries
China
Contacts
Public ContactXu Chen; Tianxin Lin
Sun Yat-sen Memorial Hospital,Sun Yat-sen University
Outcome results
None listed