Using BCG to prevent bladder cancer recurrence

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

This study is testing if a treatment called BCG can help prevent bladder cancer from coming back in adults after surgery.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 438 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd. (industry)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 36 sites (Bengbu, Anhui and 35 other locations)
• Trial ID: NCT06747455 on ClinicalTrials.gov

What this trial studies

This phase III clinical trial evaluates the efficacy and safety of Bacillus Calmette-Guérin (BCG) as a therapeutic treatment for preventing postoperative recurrence of non-muscle-invasive bladder cancer in adults aged 18 and older. The study is randomized, double-blind, and active-controlled, involving multiple centers. Participants will be assessed for recurrence-free survival rates at one and two years post-treatment, along with monitoring for adverse events and other safety measures.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with intermediate- and high-risk non-muscle-invasive bladder cancer who have undergone transurethral bladder tumor resection.

Not a fit: Patients with muscle-invasive bladder cancer or those who have visible tumors post-surgery may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the recurrence of bladder cancer in patients at high risk.

How similar studies have performed: Previous studies have shown positive outcomes with BCG treatment for bladder cancer, indicating a potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* 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, and subjects who meet the criteria for a second resection should undergo a second resection, which should be included in the study after a comprehensive evaluation of 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:

  1. 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.
  2. 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.
  3. Renal function: defined as creatinine clearance estimated according to the Cockcroft Gault formula (Appendix 2) ≥ 30mL/min;
  4. 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.

Exclusion Criteria:

* 1. Those who have immunodeficiency or damage (such as AIDS patients), are using immunosuppressive drugs, steroid hormones, etc., which may cause systemic BCG disease reaction (other hormones such as patients who are given corresponding hormone therapy after thyroid/adrenal resection can be enrolled);
* 2. Those who are allergic to BCG and its excipients;
* 3. Active tuberculosis, those who are receiving or have received anti-tuberculosis treatment within 6 months before screening;
* 4. Patients with severe cardiovascular and cerebrovascular, liver, lung, and kidney diseases at the time of screening;
* 5. Patients with other genitourinary tumors or other organ tumors at the time of screening, and no obvious tumor recurrence or progression in the past 3 years, and stable condition can be considered for inclusion, such as basal cell or squamous cell skin cancer that has been adequately treated; carcinoma in situ of the breast or cervix; Low-grade prostate cancer that is monitored without any planned therapeutic intervention (e.g., surgery, radiotherapy, or castration); and other concurrent malignancies that in the opinion of the investigator have a very low likelihood of progression;
* 6. Patients with histologically confirmed muscle-invasive, locally advanced, unresectable or metastatic urothelial carcinoma or a history of this disease (i.e., ≥ T2);
* 7. Those who have received any BCG treatment for NMIBC in the past;
* 8. Those who know or suspect that abnormal conditions such as bladder perforation occur during surgery;
* 9. Those who suspect that the surgical wound has not healed or the urinary tract mucosa is damaged;
* 10. Those who have been assessed by the investigator to be accompanied by cystitis (such as urinary frequency, urgency, dysuria, etc.), or have received other bladder infusion drugs and have severe bladder irritation, which is expected to affect the evaluation of this study;
* 11. Those who have received chemotherapy, radiotherapy, and immunotherapy within 4 weeks before the first dose (except for intravesical chemotherapy immediately after surgery);
* 12. Pregnant or lactating women;
* 13. Those who cannot guarantee effective contraception during the trial period to 6 months after the last dose;
* 14. Received treatment with other clinical trial drugs (except placebo) or clinical trial devices within 3 months before the first dose;
* 15. Those who have a history of alcoholism, drug abuse or drug abuse within 6 months before screening;
* 16. Presence of any of the following: positive human immunodeficiency virus (HIV) antibody, positive syphilis-specific antibody, active hepatitis B (hepatitis B surface antigen (HBsAg) positive and hepatitis B virus deoxyribonucleic acid (DNA) copy number ≥200 IU/mL or 1000 copies/mL), hepatitis C virus (HCV) antibody positive and HCV virus copy number higher than the upper limit of normal in the research center≥ 10\^3/mL;
* 17. Any condition that, in the opinion of the investigator, may increase the risk of the subject or interfere with the performance of the clinical trial.

Where this trial is running

Bengbu, Anhui and 35 other locations

• The First Affiliated Hospital of Bengbu Medical College — Bengbu, Anhui, China (RECRUITING)
• The First Affiliated Hospital of USTC — Hefei, Anhui, China (NOT_YET_RECRUITING)
• Beijing Chaoyang Hospital Affiliated to Capital Medical University — Beijing, Beijing, China (NOT_YET_RECRUITING)
• Peking University First Hospital — Beijing, Beijing, China (NOT_YET_RECRUITING)
• Beijing Cancer Hospital — Beijing, Beijing, China (NOT_YET_RECRUITING)
• The First Affiliated Hospital of Army Medical University — Chongqing, Chongqing, China (NOT_YET_RECRUITING)
• Chongqing University Cancer Hospital — Chongqing, Chongqing, China (NOT_YET_RECRUITING)
• Union Hospital Affiliated to Fujian Medical University — Fuzhou, Fujian, China (RECRUITING)
• Sun Yat-sen University Cancer Hospital — Guangzhou, Guangdong, China (NOT_YET_RECRUITING)
• The First Affiliated Hospital of Guangzhou Medical University — Guangzhou, Guangdong, China (NOT_YET_RECRUITING)
• Cancer Hospital Affiliated to Guangxi Medical University — Nanning, Guangxi Zhuang Autonomous Region, China (RECRUITING)
• The Second Hospital of Hebei Medical University — Shijiazhuang, Hebei, China (RECRUITING)
• Xingtai People's Hospital — Xingtai, Hebei, China (RECRUITING)
• Cancer Hospital Affiliated to Harbin Medical University — Haerbin, Heilongjiang, China (NOT_YET_RECRUITING)
• The First Affiliated Hospital of Zhengzhou University — Zhengzhou, Henan, China (NOT_YET_RECRUITING)
• Hunan Provincial Cancer Hospital — Changsha, Hunan, China (RECRUITING)
• People's Hospital of Inner Mongolia Autonomous Region — Hohhot, Inner Mongolia, China (NOT_YET_RECRUITING)
• Drum Tower Hospital Affiliated to Nanjing University School of Medicine — Nanjing, Jiangsu, China (NOT_YET_RECRUITING)
• Jiangsu Provincial Cancer Hospital — Nanjing, Jiangsu, China (NOT_YET_RECRUITING)
• The First Affiliated Hospital of Nanchang University — Nanchang, Jiangxi, China (NOT_YET_RECRUITING)
• The Second Affiliated Hospital of Soochow University — Suzhou, Jiangxsu, China (NOT_YET_RECRUITING)
• Jilin Provincial People's Hospital — Changchun, Jilin, China (NOT_YET_RECRUITING)
• The First Affiliated Hospital of China Medical University — Shenyang, Liaoning, China (NOT_YET_RECRUITING)
• Qilu Hospital of Shandong University — Jinan, Shandong, China (RECRUITING)
• The Affiliated Hospital of Qingdao University — Qingdao, Shandong, China (NOT_YET_RECRUITING)
• Yantai Yuhuangding Hospital — Yantai, Shandong, China (NOT_YET_RECRUITING)
• Fudan University Shanghai Cancer Center — Shanghai, Shanghai, China (RECRUITING)
• Huadong Hospital Affiliated to Fudan University — Shanghai, Shanghai, China (NOT_YET_RECRUITING)
• Shanghai Changhai Hospital — Shanghai, Shanghai, China (NOT_YET_RECRUITING)
• The First Hospital of Shanxi Medical University — Taiyuan, Shanxi, China (NOT_YET_RECRUITING)
• The First Affiliated Hospital of Xi'an Jiaotong University — Xian, Shanxi, China (NOT_YET_RECRUITING)
• West China Hospital, Sichuan University — Chengdu, Sichuan, China (NOT_YET_RECRUITING)
• The Second Hospital of Tianjin Medical University — Tianjin, Tianjin, China (RECRUITING)
• Yunnan Cancer Hospital — Kunming, Yunnan, China (NOT_YET_RECRUITING)
• The Second Affiliated Hospital of Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (NOT_YET_RECRUITING)
• The First Affiliated Hospital of Wenzhou Medical University — Wenzhou, Zhejiang, China (RECRUITING)

Study contacts

• Study coordinator: Wei Ding Ye, Doctor

Conditions: BCG, Bacillus Calmette-Guérin for treatment, Bladder cancer.