Investigating the Efficacy and Safety of Neoadjuvant Intravesical Instillation of Mitomycin C in Treating High-risk NMIBC Patients

Investigating the Efficacy and Safety of Neoadjuvant Intravesical Instillation of Mitomycin C Combined with En-bloc Surgery in Treating High-risk Non-muscle-invasive Bladder Cancer (NMIBC) Patients

The goal of this clinical trial is to learn if neoadjuvant intravesical instillation of mitomycin C combined with en-bloc surgery works to treat high-risk non-muscle-invasive bladder cancer (NMIBC) patients. It will also learn about the safety of neoadjuvant intravesical instillation of mitomycin C. The main questions it aims to answer are:

Does neoadjuvant intravesical instillation of mitomycin C heighten the 1-year recurrence-free survival (RFS) rate for high-risk non-muscle-invasive bladder cancer (NMIBC) patients? What medical problems do participants have when taking neoadjuvant intravesical instillation of mitomycin C? Researchers will compare neoadjuvant intravesical instillation of mitomycin C to a placebo (normal saline) to see if neoadjuvant intravesical instillation of mitomycin C works to treat high-risk NMIBC.

Participants will:

Take neoadjuvant intravesical instillation of mitomycin C or a placebo twice，1 day and 4 hours before en-bloc surgery Visit the clinic once every 8 weeks for checkups and tests Keep track of the recurrence and progression of the tumor.

Study Overview

• Status: Recruiting
• Conditions: Non-Muscle-Invasive Bladder Cancer (NMIBC)
• Intervention / Treatment: Drug: Mitomycin C (MMC); Drug: Normal Saline (Placebo)

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yang Xun, Doctor of Medicine; Phone Number: +86-27-83663460; Email: tjxyang1993@163.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Recruiting
      • Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Yang Xun; Phone Number: 027-83663460; Email: tjxyang1993@163.com
    • Wuhan, Hubei, China, 430000
      • Recruiting
      • The Central Hospital of Wuhan
      • Contact: Yonglian Guo; Phone Number: +86-027-82211521; Email: Guoyonglian662299@aliyun.com
    • Xiangyang, Hubei, China
      • Recruiting
      • Xiangyang Central Hospital
      • Contact: Bin Chen; Phone Number: +86 2812096; Email: 625848080@qq.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Voluntarily sign an informed consent form, understand the study and are willing and able to follow and complete all trial procedures
2. Gender is not limited, age between 18 to 75 years old (inclusive of boundary values)
3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
4. Previously confirmed non-muscle-invasive bladder cancer by imaging and pathology
5. In accordance with the "EAU Guidelines (2024 edition)" high-risk NMIBC patient danger grouping. All T1 HG/G3 and CIS patients except for the extremely high-risk group; Ta LG/G2 or T1G1, non-CIS with three risk factors; Ta HG/G3 or T1 LG, non-CIS with at least two risk factors; T1G2 non-CIS with at least one risk factor. (Risk factors: age > 70 years; multiple papillary tumors; tumor diameter > 3cm)
6. Participants are willing to provide the last cystoscopy biopsy specimen or specimens from the previous recurrence surgery (including paraffin blocks, paraffin-embedded sections, etc.)
7. The interval between previous anti-tumor treatments (chemotherapy, radiotherapy, immunotherapy) and the first administration of this trial is ≥6 weeks
8. Suitable organ function and hematopoietic function: Neutrophil count (NEUT ≥ 1.5 × 10^9/L; White blood cell count (WBC) ≥ 3.0 × 10^9/L; Platelet count ≥ 100 × 10^9/L; Hemoglobin ≥ 90g/L; Serum creatinine ≤ 1.5 times the upper limit of normal (ULN); AST and ALT ≤ 2.5 times ULN; Serum total bilirubin ≤ 1.5 times ULN; Activated partial thromboplastin time (APTT) ≤ 1.5 times ULN (except for patients on anticoagulant therapy)
9. Male participants must agree to use effective contraceptive measures during the treatment period and for at least 180 days after the last treatment, and must not donate sperm during this period; women of childbearing age must have a negative blood pregnancy test within 72 hours before the first new adjuvant instillation, and must agree to use effective contraceptive measures during the treatment period and for at least 180 days after en-bloc treatment

Exclusion Criteria:

1. The primary tumor is upper urinary tract urothelial carcinoma of the renal pelvis and ureter
2. Patients who have suffered from malignant tumors other than bladder urothelial carcinoma within 5 years before enrollment. However, the following patients are included (eligible for enrollment): ① Patients with locally low-risk prostate cancer (staging ≤T2b, Gleason score ≤7, and PSA ≤ 20ng/ml, with no recurrence after treatment as determined by follow-up PSA levels); ② Patients with low-risk prostate cancer (staging T1/T2a, Gleason score ≤7, and PSA ≤10ng/ml, in the observation phase without treatment; ③ Patients who meet other enrollment criteria but have very low risk of metastasis or death from malignant tumors, and who show no recurrence or metastasis after standard treatment, as confirmed by imaging and disease-specific tumor marker tests, such as fully treated carcinoma in situ of the cervix, basal or squamous cell skin cancer; in situ ductal carcinoma after treatment surgery, etc
3. Patients with active autoimmune diseases who have required systemic treatment (i.e., long-term use of corticosteroids or immunosuppressive drugs) within the past two years. Replacement therapy (such as thyroid hormone, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency) is excluded
4. Patients who are expected to have major surgery during the study period or who have undergone major surgery within 4 weeks before dosing and have not fully recovered
5. Any immune-related toxicity caused by previous cancer treatments has not recovered to ≤Grade 1 (except for Grade 2 endocrine disorders on stable dose steroid replacement therapy), and/or any other toxicity related to previous anti-cancer treatments (immune-related toxicity excluded) has not recovered to ≤Grade 2, except for alopecia
6. Patients who are seropositive for Human Immunodeficiency Virus (HIV) or have a history of HIV infection or other acquired immunodeficiency diseases
7. Patients who require long-term antiviral medication for hepatitis B or C, where hepatitis B (must meet both HBsAg positivity and HBV DNA ≥2000 IU/ml, excluding drug or other causes of hepatitis), hepatitis C (must meet both anti-HCV antibody positivity and HCV-RNA results greater than the lower limit of detection)
8. Uncontrolled stable systemic diseases, such as cardiovascular and cerebrovascular diseases, diabetes, etc
9. History of organ transplantation or stem cell transplantation
10. Heart failure (patients classified as NYHA Class III-IV according to the New York Heart Association)
11. Significant pulmonary disease (such as shortness of breath at rest or with mild activity or requiring oxygen for any reason)
12. Other underlying diseases judged by the investigator before the study that prevent the use of study medication or interfere with disease diagnosis, or have the potential to cause serious complications
13. Concurrent other serious infections before dosing
14. Alcohol dependence or a history of drug or substance abuse within the last year
15. A history of clear neurological or psychiatric disorders, such as epilepsy, dementia, poor compliance, or the presence of peripheral nervous system disorders
16. Pregnancy or breastfeeding, or expected to be pregnant or give birth during the trial period
17. Known allergy or intolerance to intravenous mitomycin and corresponding excipients
18. Patients whom the investigator deems unsuitable for the trial for other reasons

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neoadjuvant intravesical instillation mitomycin C combined with en-bloc surgery	Drug: Mitomycin C (MMC); When administering neoadjuvant intravesical instillations, instruct the patient to lie flat on the treatment bed and cover with a waterproof pad. Disinfect the perineal area 2-3 times. Under sterile conditions, insert a catheter and drain the bladder of urine completely. Slowly instill the prepared instillation solution (mitomycin) into the bladder. If the patient experiences pain during the instillation, stop the infusion immediately, and continue when the pain subsides. If the patient still cannot tolerate it, discontinue the instillation treatment for this session. After the medication is instilled into the bladder, the catheter can be removed immediately or left in place. Instruct the patient to hold their urine for as long as possible under suitable conditions for 2 hours, and to change positions intermittently while the medication is retained in the bladder. The neoadjuvant intravesical instillation cycle is twice (one day and 4 h before en-bloc surgery）
Placebo Comparator: Neoadjuvant intravesical instillation normal saline combined with en-bloc surgery	Drug: Normal Saline (Placebo); When administering neoadjuvant intravesical instillations, instruct the patient to lie flat on the treatment bed and cover with a waterproof pad. Disinfect the perineal area 2-3 times. Under sterile conditions, insert a catheter and drain the bladder of urine completely. Slowly instill the prepared instillation solution (Normal Saline) into the bladder. If the patient experiences pain during the instillation, stop the infusion immediately, and continue when the pain subsides. If the patient still cannot tolerate it, discontinue the instillation treatment for this session. After the medication is instilled into the bladder, the catheter can be removed immediately or left in place. Instruct the patient to hold their urine for as long as possible under suitable conditions for 2 hours, and to change positions intermittently while the medication is retained in the bladder. The neoadjuvant intravesical instillation cycle is twice (one day and 4 h before en-bloc surgery）

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year recurrence-free survival rate	The one-year recurrence-free survival rate, as assessed by researchers, is defined as the proportion of patients who are free of tumor recurrence at one year after randomization. Recurrence is defined as any pathological level of urothelial carcinoma confirmed by cystoscopy and biopsy during the one-year follow-up period starting from the time of randomization.	One year after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	This was determined by cystoscopy and pathology every eight weeks for one year and telephone follow-up every one year after one year until tumor progression and patient death from any cause, or five years after the end of the study. Defined as the time between the start of randomization and progression of disease or death from any cause, whichever occurs first. Disease progression was defined as an increase in bladder tumors from Ta/T1 to T1/ T2 or larger, lymph node metastasis and distant metastasis, or an increase in tumor grade from low to high.	Every eight weeks for one year and telephone follow-up every one year after one year until tumor progression and patient death from any cause, or five years after the end of the study.
overall survival	Telephone follow-up was conducted every 1 year after the start of randomization until death from any cause or 5 years after the end of the study.	up to 5 years after the end of the study.
Health-related quality of life	The health-related quality of life of the patients was assessed by EORTC QLQ-C30	up to One year after discharge
Adverse event	Adverse events were coded using the International Dictionary of Medical Terms (MedDRA), and adverse events (TEAE) during treatment were aggregated by Systematic Organ Classification (SOC), Preferred term (PT), and NCI-CTCAE grading. The number, frequency and incidence of adverse events and drug-related adverse events of all subjects were counted. Make a list of adverse events. This is determined by interview, physical examination, as well as the patient's vital signs and laboratory tests.	up to Eight weeks after discharge

Collaborators and Investigators

• Sponsor: Shaogang Wang

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2031

Study Registration Dates

• First Submitted: November 17, 2024
• First Submitted That Met QC Criteria: November 19, 2024
• First Posted (Actual): November 20, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 17, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: mitomycin C; high-risk non-muscle-invasive bladder cancer; neoadjuvant intravesical instillation; en-bloc surgery
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Urologic Neoplasms; Carcinoma; Urinary Bladder Diseases; Non-Muscle Invasive Bladder Neoplasms; Urinary Bladder Neoplasms; Antibiotics, Antineoplastic; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors; Alkylating Agents; Mitomycins; Mitomycin
• Other Study ID Numbers: 2024TJCR012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No