Efficacy of Gemcitabine Submucosal Injection for Preventing Recurrence in Intermediate- and High-Risk Non-Muscle-Invasive Bladder Cancer: A Randomized Trial

NCT ID: NCT07198451

Last Updated: 2025-09-30

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 320 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-10-31
• Study Completion Date: 2028-06-30

Brief Summary

Bladder cancer is the most common malignant tumor of the urinary system in China, and its incidence has been increasing year by year. It is classified into non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). NMIBC accounts for 75% of newly diagnosed bladder cancer cases, and transurethral resection of bladder tumor (TURBT) followed by postoperative intravesical therapy is the standard treatment for NMIBC. However, the 5-year recurrence rate of NMIBC remains as high as 50%, with 20-30% of patients progressing to MIBC. MIBC is characterized by rapid progression and a high tendency for metastasis. The 5-year survival rate for patients with metastatic bladder cancer is only 5.4%. This study aims to investigate the efficacy of submucosal injection of the chemotherapeutic agent gemcitabine in preventing recurrence of intermediate- and high-risk NMIBC. Additionally, it seeks to develop software and devices related to submucosal injection to promote the clinical application of this new approach in the chemotherapeutic management of NMIBC. This research is expected to bring a revolutionary breakthrough in the standardisation of whole-process diagnosis and treatment of NMIBC, holding significant scientific value and major clinical translational importance for improving therapeutic outcomes and prognosis of bladder cancer.

Detailed Description

Bladder cancer is a common malignant tumor of the urinary system. Globally, in 2023, there were approximately 610,000 new cases of bladder cancer and about 220,000 deaths attributed to the disease. In China, over the past two decades, the age-standardized incidence and prevalence rates of bladder cancer in men have increased by 71.79% and 195.38%, respectively. Over the last 15 years, the average annual mortality rate for male bladder cancer has risen by 3.84%, posing a serious threat to public health.

Bladder cancer is classified into non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) based on whether the tumor invades the muscle layer. NMIBC accounts for approximately 75% of newly diagnosed bladder cancer cases. The standard treatment for NMIBC involves transurethral resection of bladder tumor (TURBT) followed by postoperative intravesical therapy. However, NMIBC often recurs within one year, with a recurrence rate as high as 60-70%, and 20-30% of cases progress to MIBC. Once bladder cancer advances to MIBC, it is characterized by rapid progression and a high tendency for metastasis. The standard treatment for MIBC is radical cystectomy with lymph node dissection, often accompanied by neoadjuvant or adjuvant chemotherapy. Traditional radical surgery for bladder cancer is highly invasive, associated with slow postoperative recovery and a high incidence of complications. The objective response rate for neoadjuvant or adjuvant chemotherapy is less than 50%. The 5-year survival rate for MIBC is below 60%, and for patients with distant metastasis, it drops significantly to just 5.4%.

In recent years, cancer immunotherapy, particularly immune checkpoint inhibitors, has advanced rapidly. However, immunotherapy also suffers from a low objective response rate, which is even below 30% in MIBC. Therefore, the high incidence, recurrence rate, and difficulty in curing bladder cancer remain significant challenges for both clinicians and patients.

TURBT is the standard surgical procedure for NMIBC. Intravesical therapy is a local adjuvant treatment used after TURBT to prevent recurrence. However, the efficacy of intravesical therapy is limited by inadequate drug absorption, resulting in insufficient local drug concentrations and suboptimal therapeutic outcomes. Moreover, postoperative intravesical therapy involves long-term, repeated invasive procedures, which often lead to complications such as urinary tract infections, bladder irritation, and urethral strictures. Improving the efficiency of drug utilization in intravesical therapy is a promising approach to address these issues. Enhancing drug absorption and prolonging the sustained-release effect of the agents could improve treatment efficacy while reducing the frequency of intravesical instillations, ultimately improving the prognosis of NMIBC, lowering recurrence rates, and reducing the risk of progression to MIBC. Submucosal injection of chemotherapeutic drugs offers a potential solution by increasing drug utilization efficiency and reducing complications associated with intravesical therapy.

Conditions

Non Muscle Invasive Bladder Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Gemcitabine Submucosal Injection Arm

Patients in this arm will receive submucosal injections of gemcitabine following transurethral resection of bladder tumor (TURBT). The regimen consists of one injection immediately after TURBT, followed by additional injections once every three months, for a total of four injections. Each injection uses 1000mg of gemcitabine. Injection sites are planned based on bladder area and common tumor locations, administered using a specialized injection gun.

Group Type: EXPERIMENTAL

Gemcitabine Submucosal Injection

Intervention Type: DRUG

A chemotherapeutic agent. Administered via submucosal injection into the bladder wall using a specialized injection gun. Dosage: 1000mg per injection. Regimen: One injection immediately post-TURBT, followed by one injection every three months for a total of four injections.

Gemcitabine Intravesical Instillation Arm

Patients in this arm will receive standard intravesical instillation of gemcitabine following TURBT. The regimen consists of one instillation immediately after surgery, followed by an induction phase of once-weekly instillations for eight weeks, and then a maintenance phase of once-monthly instillations for ten months. Each instillation uses 2000mg of gemcitabine dissolved in 50mL of normal saline, retained for 30-60 minutes.

Group Type: ACTIVE_COMPARATOR

Gemcitabine Intravesical Instillation

Intervention Type: DRUG

Standard therapy. Administered by instilling a solution into the bladder via a catheter. Dosage: 2000mg dissolved in 50mL normal saline per instillation. Regimen: One instillation immediately post-TURBT, followed by an induction phase (once weekly for 8 weeks) and a maintenance phase (once monthly for 10 months). The solution is retained for 30-60 minutes.

Interventions

Gemcitabine Submucosal Injection

A chemotherapeutic agent. Administered via submucosal injection into the bladder wall using a specialized injection gun. Dosage: 1000mg per injection. Regimen: One injection immediately post-TURBT, followed by one injection every three months for a total of four injections.

Intervention Type: DRUG

Gemcitabine Intravesical Instillation

Standard therapy. Administered by instilling a solution into the bladder via a catheter. Dosage: 2000mg dissolved in 50mL normal saline per instillation. Regimen: One instillation immediately post-TURBT, followed by an induction phase (once weekly for 8 weeks) and a maintenance phase (once monthly for 10 months). The solution is retained for 30-60 minutes.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patients aged 18 to 80 years (inclusive) with radiologically confirmed bladder tumor and scheduled to undergo transurethral resection of bladder tumor (TURBT).

2. Postoperative pathological confirmation of intermediate- or high-risk non-muscle-invasive bladder cancer (NMIBC).

3. Voluntarily participate in the study and sign the informed consent form, ensuring the patient fully understands the trial purpose, risks, and right to withdraw.

Exclusion Criteria

1. Preoperative comorbidities including detrusor overactivity, urethral stricture, urge incontinence, stress incontinence, or overflow incontinence.

2. Concurrent urogenital infectious diseases (e.g., acute urethritis, acute cystitis).

3. History of pelvic radiotherapy.

4. Receiving systemic anti-tumor therapy for any malignant tumor.

5. Severe cardiovascular disease, hepatic or renal insufficiency, or coagulation dysfunction.

6. Presence of mental illness or psychological disorders that impair normal communication.

7. Any other situation deemed by the investigator as unsuitable for participation in this clinical study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai University of Traditional Chinese Medicine

OTHER

Sponsor Role: lead

Responsible Party

Naiwen Chen

Resident physicians

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dongliang Xu

Role: PRINCIPAL_INVESTIGATOR

Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

Central Contacts

Naiwen Chen

Role: CONTACT

climb2021@163.com

+8615858384378

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Other Identifiers

2025-1871-211-01

Identifier Type: -

Identifier Source: org_study_id