Clinical Trial for Evaluating the Efficacy and Safety of BCG for Therapeutic Use in the Prevention of Postoperative Recurrence of Medium/High-risk Non-muscle Invasive Bladder Cancer (NMIBC)

Summary

A phase III multi-center randomized, double-blind and positive-controlled clinical trial for evaluating the efficacy and safety of BCG for Therapeutic Use（BCG） in the prevention of postoperative recurrence of medium/high-risk non-muscle invasive bladder cancer (NMIBC).

Eligibility

Inclusion Criteria:

* 1\. Male or female patients aged ≥18 year and ≤75 year
* 2\. According to the stipulations of Guidelines on Diagnosing \& Treating Bladder Cancer (Edition 2022) as promulgated by National Health Commission, an initial definite diagnosis of medium/high-risk non-muscle invasive urothelial bladder cancer (T1/Ta/Tis) as confirmed by histological examination and requiring an adjuvant therapy of BCG bladder instillation；
* 3\. After a thorough TURBt, all tumors should be grossly invisible. Patients requiring a second procedure are also eligible for inclusion. Those fulfilling the requirements of a second procedure may do so. Patients fulfilling the requirements of a second procedure shall meet the following criteria:

  1. Criteria of a second TURBt: 1) Initial TURBt is insufficient; 2) No muscular specimen during an initial TURBt; 3) Stage T1 tumor; 4) G3 (advanced grade) tumor, except for simple in situ tumor;
  2. A second TURBt is recommended within Weeks 2-6 after an initial procedure. It is optimal at Week 4. After TURBt until BCG bladder instillation, no other instillations are allowed except for 1st/2nd immediate instillation chemotherapeutic agents. For the last TURBt, only epirubicin is reserved for immediate instillation chemotherapy;
  3. Subjects undergoing a second TURBt and starting BCG therapy at Weeks 2-4 after a second procedure;
  4. Based upon the first/second result of histopathology examination, comprehensively evaluating whether or not a certain patient is eligible for inclusion.
* 4\. A previous history of never receiving any therapy of BCG bladder instillation;
* 5\. ECOG score: 0-2 points;
* 6\. Clinical laboratory tests fulfilling the following features:

  1. Blood routine: Within Day 14 prior to randomization, never using any hematopoietic growth factor or blood transfusion, including absolute neutrophil count (ANC) ≥1500/mm3 or ≥1.5×109/L; platelet ≥100000/mm3 or 100×109/L; hemoglobin ≥9 g/dL.
  2. Liver function: total serum bilirubin ≤1.5× upper limit of normal (ULN); for subjects with Gilbert syndrome total serum bilirubin \<3×ULN ;AST/ALT ≤2.5×ULN.
  3. Renal function: defined as estimated creatinine clearance ≥50 mL/min according to the formula of Cockcroft-Gault;
  4. Blood coagulation function: APTT ≤ 1.5×ULN and INR ≤1.5×ULN.
* 7\. Capable of understanding the procedures and methods of clinical study and participating voluntarily after offering thorough informed consents.

Exclusion Criteria:

* 1\. Current users of immune suppressants, hormones or radiotherapy and potentially causing systemic BCG-related disease responses (patients requiring an injection of matching hormones after thyroidectomy or adrenalectomy are also eligible for inclusion);
* 2\. Allergic to BCG or its analogues;
* 3\. Presence of active TB lesions, currently receiving an anti-TB therapy or taking any anti-TB regimen within Month 6 prior to screening;
* 4\. Known or suspected intraoperative bladder perforation;
* 5\. Presence of severe gross hematuria pre-dosing as judged by investigators and with a suspicion of non-healing surgical wound;
* 6\. Presence of concurrent cystitis with such signs of cystic irritation as urinary frequency/urgency/pain as judged by investigators or previously receiving therapies of other bladder instillation drugs and irritating bladder signs severe enough to interfere with study evaluations;
* 7\. Individuals with a previous history of such severe adverse events as BCG sepsis or systemic infections;
* 8\. Complete cystic urinary incontinence is defined as using six and more pads with 24h;
* 9\. Concurrently with other urogenital system tumors or other malignant solid organ tumors;
* 10\. Individuals with a previous history of severe cerebrocardiovascular, pulmonary, hepatic and renal diseases or hypertension and diabetes mellitus clinically uncontrollable as judged by investigators;
* 11\. Individuals with an evidence of focal advanced or metastatic muscular infiltration urothelial cancer or concurrent extra-cystic non-muscle invasive urothelial transition cell cancer;
* 12\. Receiving chemotherapy, radiotherapy or immunotherapy within Week 4 prior to an initial dose (except for immediate postoperative intravesical chemotherapy);
* 13\. Pregnant or lactating women;
* 14\. Individuals failing to adopt effective birth control measures during study until Month 6 after the last dose;
* 15\. Participating in a clinical study of another drug within Month 3 prior to screening;
* 16\. Known dependents of opioids or alcohol;
* 17\. Any of the following items: Positive antibodies of (HIV, treponema pallidum and acute/chronic active hepatitis B (HBsAg); copy number of HBV-DNA in peripheral blood ≥103/mL; HCV antibody positive with copy number of HCV ≥103 /mL;
* 18\. Individuals with mental retardations or poor compliance;
* 19\. Any circumstance potentially boosting subject risks or interfering with study implementations as judged by investigators.

Conditions2

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