Multicenter Clinical Trial on the Effectiveness and Safety of Instillation of BCG and Alternative BCG Protocols for Intermediate and High-risk Non-muscle Invasive Bladder Cancer

Multicentre Clinical Trial of the Efficacy and Safety of Tislelizumab in Combination With BCG Bladder Instillation in the Prevention of Postoperative Recurrence in Intermediate and High-risk Non-muscle Invasive Bladder Cancer

Previous studies have reported the efficacy of Bacillus Calmette-Guérin (BCG) combined with other drugs for the treatment of bladder cancer. However, research on the combination of tislelizumab and BCG for bladder cancer treatment has largely been retrospective. Currently, ongoing clinical trials have not discussed the effectiveness of PD-1/PD-L1 inhibitors combined with BCG instillation in reducing postoperative recurrence in intermediate-risk NMIBC. Therefore, this study aims to explore the clinical efficacy and safety of tislelizumab combined with BCG in the treatment of intermediate and high-risk NMIBC. For this purpose, investigators have established strict screening criteria to include eligible patients in the study and have recruited suitable patients from multiple medical centers.Investigators have also developed a meticulous implementation process and follow-up considerations, hoping to better verify the clinical efficacy and safety of the combined use of these two drugs.

Study Overview

• Status: Recruiting
• Conditions: Urinary Bladder Neoplasms; Treatment Outcome; Neoplasm Recurrence, Local; Multicenter Study; Immunotherapy, Active; BCG Vaccine
• Intervention / Treatment: Drug: Tislelizumab in Combination with Bacillus Calmette-Guérin

• Study Type: Interventional
• Enrollment (Estimated): 76
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jiabing Zheng; Phone Number: +8613799422519; Email: xhyykjk@163.com

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350000
      • Recruiting
      • Department of Urology, Fujian Union Hospital, Fujian Medical University
      • Contact: Jiabing Zheng; Phone Number: +8613799422519; Email: xhyykjk@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntary participation in the trial with signed informed consent;
2. Patients aged ≥18 and ≤75 years, regardless of gender, with an expected survival of ≥2 years;
3. Histologically confirmed non-muscle-invasive bladder urothelial carcinoma with positive PD-L1 expression. According to the 2014 guidelines of the Chinese Urological Association (CUA), patients are assessed as having a medium to high risk of recurrence or progression. (For patients considering a second transurethral resection, they may be included in the study after completing the procedure and if pathology confirms medium to high risk non-muscle-invasive bladder urothelial carcinoma);
4. Performance status score (Eastern Cooperative Oncology Group, ECOG) of 0-2;
5. Completion of screening-related examinations (complete blood count, coagulation function, liver and kidney function, infectious disease screening, 12-lead ECG, urinary system ultrasound, pelvic MR, and tissue pathology examination), without surgical contraindications.

Exclusion Criteria:

1. Any of the following conditions:

   Immune deficiency or impairment (such as AIDS patients), current use of immunosuppressive drugs or radiation therapy that may cause systemic BCG disease reaction; allergy to BCG components; patients with fever and acute infectious diseases, including active tuberculosis or those undergoing anti-tuberculosis treatment; those with severe chronic cardiovascular or cerebrovascular diseases or chronic kidney disease;

2. Concurrent urogenital system tumors or tumors in other organs;
3. Muscle-invasive bladder urothelial carcinoma (stage T2 and above) patients;
4. Patients who have received chemotherapy, radiotherapy, or immunotherapy within the past 4 weeks (except immediate postoperative bladder instillation chemotherapy);
5. Pregnant or lactating women, women of childbearing age not using effective contraception, or those planning to conceive during the trial period (including male participant partners);
6. Known or suspected intraoperative bladder perforation;
7. Presence of gross hematuria prior to enrollment, suspected unhealed surgical wounds or damaged urinary mucosa;
8. Severe urethral stricture preventing cystoscopy, history of bladder contracture, or functional bladder volume less than 100mL;
9. Accompanying cystitis, or those who have received other bladder instillation medications and have severe bladder irritation signs expected to affect the assessment of this study;
10. Patients with various mental disorders, severe coagulation function, liver and kidney function, hematopoietic function disorders, etc., that cannot tolerate surgical treatment;
11. Participation in other drug clinical trials within 3 months before enrollment;
12. Known or suspected opioid or alcohol dependence;
13. Any condition that the researcher believes may increase the risk to the participant or interfere with the execution of the clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Postoperative Instillation Therapy Group; Tislelizumab in Combination with Bacillus Calmette-Guérin for the Treatment of Intermediate and High-Risk NMIBC Group

Drug: Tislelizumab in Combination with Bacillus Calmette-Guérin; Postoperative immediate instillation of epirubicin (50mg) is administered. Postoperatively, 200mg of tislelizumab injection is given intravenously every 3 weeks, with each 21-day period constituting one cycle. The medication is administered on day 1 of each cycle, continuing for one year. Eligible patients for the single-arm group (N = 76) begin BCG instillation after 2 weeks, with a dosage of 120mg per instillation, totaling 19 instillations: this starts with a 6-week induction phase of weekly BCG instillations, followed by BCG instillations every 2 weeks for three consecutive times; thereafter, maintenance instillation therapy commences, involving monthly BCG instillations for a total of ten times.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse-Free Survival(RFS)	The time from postoperative cystoscopic examination to the first documented recurrence of bladder tumor.	From date of postoperative cystoscopic examination to the first documented recurrence of bladder tumor,assessed up to 60 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival(PFS)	The time recorded from postoperative cystoscopic and pathological examinations to the first progression of bladder tumor, defined in this trial as the occurrence of muscle-invasive growth in NMIBC (Non-Muscle Invasive Bladder Cancer) patients.	From date of postoperative cystoscopic and pathological examinations to the first progression of bladder tumor, assessed up to 60 months.
Overall survival	The duration from post-surgery to the time of death due to any cause. For participants who are lost to follow-up prior to death, the time of their last follow-up is typically considered as the time of death for calculation purposes.	From date of post-surgery to the time of death due to any cause,assessed up to 60 months
Adverse event（AS)	An adverse event (AE) is defined according to the toxicity grading standards set by the National Cancer Institute of the United States. This includes a spectrum of adverse reactions associated with antineoplastic therapy. Specific grading of adverse reactions refers to the Common Terminology Criteria for Adverse Events (CTCAE Version 5.0) developed by the National Cancer Institute (NCI).	From date of post-surgery to the time of death due to any cause,assessed up to 60 months.

Collaborators and Investigators

• Sponsor: Fujian Medical University Union Hospital
• Investigators: Principal Investigator: Zhenlin Chen, Department of Urology, Fujian Union Hospital, Fujian Medical University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2023
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2035

Study Registration Dates

• First Submitted: May 14, 2024
• First Submitted That Met QC Criteria: June 3, 2024
• First Posted (Estimated): June 4, 2024

Study Record Updates

• Last Update Posted (Estimated): June 4, 2024
• Last Update Submitted That Met QC Criteria: June 3, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Urinary Bladder Diseases; Disease Attributes; Neoplastic Processes; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Neoplasms; Recurrence; Urinary Bladder Neoplasms; Neoplasm Recurrence, Local; Non-Muscle Invasive Bladder Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Adjuvants, Immunologic; BCG Vaccine; Tislelizumab
• Other Study ID Numbers: 2023XHYG0045-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No