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

NCT07198451 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: 2025-1871-211-01
• Study Type: interventional
• Target: 320
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Non Muscle Invasive Bladder Cancer

Keywords

non muscle invasive bladder cancer; Gemcitabine; Submucosal Injection; Recurrence; Randomized Controlled Trial

Outcome Measures

Primary Outcomes (1)

• 24-month Bladder Tumor Recurrence Rate

  The proportion of patients with bladder tumor recurrence confirmed by cystoscopy and tissue biopsy within 24 months after transurethral resection of bladder tumor (TURBT). The recurrence rate is calculated as: (Number of patients with confirmed recurrence in the group / Total number of analyzed patients in that group) × 100%.

  24 months post-operation

Secondary Outcomes (5)

• Proportion of Pathological Grade Upgrading upon Recurrence

  Through study completion, up to 60 months

• Tumor Complete Response (CR) Rate

  Through study completion, up to 60 months

• Incidence of Bladder Irritation Symptoms and Gross Hematuria

  Through study completion, up to 60 months

• Change in Quality of Life Core Questionnaire (QLQ-C30) Score

  Through study completion, up to 60 months

• Change in Bladder Cancer-Specific Module (QLQ-BLM30) Score

  Through study completion, up to 60 months

Study Arms (2)

Gemcitabine Submucosal Injection Arm

EXPERIMENTAL

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.

Drug: Gemcitabine Submucosal Injection

Gemcitabine Intravesical Instillation Arm

ACTIVE COMPARATOR

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.

Drug: Gemcitabine Intravesical Instillation

Interventions

Gemcitabine Submucosal Injection 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 Submucosal Injection Arm

Gemcitabine Intravesical Instillation 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.

Gemcitabine Intravesical Instillation Arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 18 to 80 years (inclusive) with radiologically confirmed bladder tumor and scheduled to undergo transurethral resection of bladder tumor (TURBT).
• Postoperative pathological confirmation of intermediate- or high-risk non-muscle-invasive bladder cancer (NMIBC).
• Voluntarily participate in the study and sign the informed consent form, ensuring the patient fully understands the trial purpose, risks, and right to withdraw.

You may not qualify if:

• Preoperative comorbidities including detrusor overactivity, urethral stricture, urge incontinence, stress incontinence, or overflow incontinence.
• Concurrent urogenital infectious diseases (e.g., acute urethritis, acute cystitis).
• History of pelvic radiotherapy.
• Receiving systemic anti-tumor therapy for any malignant tumor.
• Severe cardiovascular disease, hepatic or renal insufficiency, or coagulation dysfunction.
• Presence of mental illness or psychological disorders that impair normal communication.
• Any other situation deemed by the investigator as unsuitable for participation in this clinical study.

Sponsors & Collaborators

• Shanghai University of Traditional Chinese Medicine: lead

Related Publications (12)

• Liu K, Peng J, Guo Y, Li Y, Qi X, Duan D, Li T, Li J, Niu Y, Han G, Zhao Y. Expanding the Potential of Neoantigen Vaccines: Harnessing Bacille Calmette-Guerin Cell-Wall-Based Nanoscale Adjuvants for Enhanced Cancer Immunotherapy. ACS Nano. 2024 May 7;18(18):11910-11920. doi: 10.1021/acsnano.4c01691. Epub 2024 Apr 29.

  PMID: 38680054 BACKGROUND

• Koya MP, Simon MA, Soloway MS. Complications of intravesical therapy for urothelial cancer of the bladder. J Urol. 2006 Jun;175(6):2004-10. doi: 10.1016/S0022-5347(06)00264-3.

  PMID: 16697786 BACKGROUND

• Gravestock P, Cullum D, Somani B, Veeratterapillay R. Diagnosing upper tract urothelial carcinoma: A review of the role of diagnostic ureteroscopy and novel developments over last two decades. Asian J Urol. 2024 Apr;11(2):242-252. doi: 10.1016/j.ajur.2022.08.003. Epub 2022 Sep 23.

  PMID: 38680592 BACKGROUND

• Morad G, Helmink BA, Sharma P, Wargo JA. Hallmarks of response, resistance, and toxicity to immune checkpoint blockade. Cell. 2021 Oct 14;184(21):5309-5337. doi: 10.1016/j.cell.2021.09.020. Epub 2021 Oct 7.

  PMID: 34624224 BACKGROUND

• Kartolo A, Robinson A, Vera Badillo FE. Can Oncogenic Driver Alterations be Responsible for the Lack of Immunotherapy Efficacy in First-line Advanced Urothelial Carcinoma? Eur Urol. 2023 Jan;83(1):1-2. doi: 10.1016/j.eururo.2022.04.022. Epub 2022 May 20.

  PMID: 35606230 BACKGROUND

• Powles T, Park SH, Voog E, Caserta C, Valderrama BP, Gurney H, Kalofonos H, Radulovic S, Demey W, Ullen A, Loriot Y, Sridhar SS, Tsuchiya N, Kopyltsov E, Sternberg CN, Bellmunt J, Aragon-Ching JB, Petrylak DP, Laliberte R, Wang J, Huang B, Davis C, Fowst C, Costa N, Blake-Haskins JA, di Pietro A, Grivas P. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2020 Sep 24;383(13):1218-1230. doi: 10.1056/NEJMoa2002788. Epub 2020 Sep 18.

  PMID: 32945632 BACKGROUND

• Advanced Bladder Cancer (ABC) Meta-analysis Collaborators Group. Adjuvant Chemotherapy for Muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis of Individual Participant Data from Randomised Controlled Trials. Eur Urol. 2022 Jan;81(1):50-61. doi: 10.1016/j.eururo.2021.09.028. Epub 2021 Nov 19.

  PMID: 34802798 BACKGROUND

• Cambier S, Sylvester RJ, Collette L, Gontero P, Brausi MA, van Andel G, Kirkels WJ, Silva FC, Oosterlinck W, Prescott S, Kirkali Z, Powell PH, de Reijke TM, Turkeri L, Collette S, Oddens J. EORTC Nomograms and Risk Groups for Predicting Recurrence, Progression, and Disease-specific and Overall Survival in Non-Muscle-invasive Stage Ta-T1 Urothelial Bladder Cancer Patients Treated with 1-3 Years of Maintenance Bacillus Calmette-Guerin. Eur Urol. 2016 Jan;69(1):60-9. doi: 10.1016/j.eururo.2015.06.045. Epub 2015 Jul 23.

  PMID: 26210894 BACKGROUND

• Comperat E, Amin MB, Cathomas R, Choudhury A, De Santis M, Kamat A, Stenzl A, Thoeny HC, Witjes JA. Current best practice for bladder cancer: a narrative review of diagnostics and treatments. Lancet. 2022 Nov 12;400(10364):1712-1721. doi: 10.1016/S0140-6736(22)01188-6. Epub 2022 Sep 26.

  PMID: 36174585 BACKGROUND

• Lopez-Beltran A, Cookson MS, Guercio BJ, Cheng L. Advances in diagnosis and treatment of bladder cancer. BMJ. 2024 Feb 12;384:e076743. doi: 10.1136/bmj-2023-076743.

  PMID: 38346808 BACKGROUND

• Qi J, Li M, Wang L, Hu Y, Liu W, Long Z, Zhou Z, Yin P, Zhou M. National and subnational trends in cancer burden in China, 2005-20: an analysis of national mortality surveillance data. Lancet Public Health. 2023 Dec;8(12):e943-e955. doi: 10.1016/S2468-2667(23)00211-6.

  PMID: 38000889 BACKGROUND

• Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263. doi: 10.3322/caac.21834. Epub 2024 Apr 4.

  PMID: 38572751 BACKGROUND

MeSH Terms

Conditions

Non-Muscle Invasive Bladder Neoplasms; Recurrence

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Dongliang Xu

  Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Naiwen Chen

CONTACT

+8615858384378; climb2021@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Resident physicians

Study Record Dates

• First Submitted: September 22, 2025
• First Posted: September 30, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: September 30, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: IPD and supporting documents will become available following the publication of the primary results in a peer-reviewed journal. There is no end date for data sharing.
• Access Criteria: Data will be accessible to researchers who provide a methodologically sound proposal for approved purposes. Proposals should be directed to the corresponding author. Requestors will need to sign a data access agreement to gain access. A committee led by the principal investigator will review proposals.