A Randomized, Double-blind, Active-controlled, Multicenter Phase III Clinical Trial Evaluating the Efficacy and Safety of Therapeutic BCG for the Prevention of Postoperative Recurrence of Non-muscle-invasive Bladder Cancer in People Aged 18 Years and Older
Objectives: Primary Objectives: To assess the effectiveness of BCG for therapeutic use in the adjuvant treatment of intermediate- and high-risk NMIBC after transurethral resection of bladder tumors. Secondary Purpose: To assess the safety of the therapeutic BCG vaccine in the adjuvant treatment of intermediate- and high-risk NMIBC after transurethral resection of bladder tumors. Other purposes: To assess the pharmacodynamic (PD) profile of BCG for therapeutic use in the adjuvant treatment of intermediate- and high-risk NMIBC after transurethral resection of bladder tumors. Study design: This study adopts a randomized, double-blind, active-controlled, multi-center trial design, including three phases: screening period, treatment period and follow-up period. In this study, 438 subjects will be randomly assigned to the experimental group and the control group in a 1:1 ratio, with 219 patients in both the experimental group and the control group, and stratified according to the baseline risk level (high-risk/intermediate-risk) and whether or not to perform urine PD sample collection (yes/no).
• 1\. Age≥ 18 years old, male or female;
• 2\. According to the Guidelines for the Diagnosis and Treatment of Bladder Cancer (2022 Edition), the initial histological diagnosis of intermediate- and high-risk non-muscle-invasive urothelial carcinoma of the bladder (T1, Ta or Tis) and the need for BCG bladder infusion adjuvant therapy is evaluated;
• 3\. Patients undergoing transurethral bladder tumor resection need to meet the requirements of all tumors to have no visible tumors after surgery. This study can also enroll patients who need a second electroresection, subjects who meet the secondary electroresection criteria are recommended to undergo secondary electroresection and should be included in the study after comprehensive evaluation based on the two pathological results (BCG perfusion for treatment should be carried out within 2\
∙ 12 weeks after surgery, cystoscopy should be added more than 4 weeks after surgery to ensure that there is no visible tumor after surgery, and the subjects who underwent secondary resection should be calculated based on the postoperative time of the second electroresection); Note: The criteria for the second resection: (1) the first TURBt is insufficient; (2) the first electrosection of non-myometrial tissue specimens; (3) T1 tumors; (4) High-grade (G3) tumors, except for carcinoma in situ. The second resection is recommended to be performed within 2-6 weeks after the first resection, and no other perfusion therapy is allowed except for the bladder infusion chemotherapy drugs immediately after the first and second resection;
• 4\. Eastern Cooperative Oncology Group (ECOG) score (see Appendix 1 for details): 0\
∙ 2 points;
• 5\. At screening, clinical laboratory tests meet the following characteristics:
‣ Blood routine: no use of hematopoietic growth factors or blood transfusion support within 14 days before randomization, including: absolute neutrophil count (ANC) ≥1500/mm\^3 or ≥1.5×10\^9/L; Platelets≥ 100000/mm\^3 or 100×10\^9/L; Hemoglobin ≥ 9 g/dL.
⁃ Liver function: total bilirubin ≤ 1.5× upper limit of normal range (ULN), subjects with Gilbert's syndrome require total bilirubin \<3×ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5×ULN.
⁃ Renal function: defined as creatinine clearance estimated according to the Cockcroft Gault formula (Appendix 2) ≥ 30mL/min;
⁃ Coagulation function: activated partial thromboplastin time (APTT) ≤ 1.5×ULN, and the international normalized ratio (INR) ≤ 1.5×ULN.
• 6\. Voluntarily participate in this trial, with full informed consent and signed written informed consent.