Clinical trial NCT06696794: Investigating the Efficacy and Safety of Neoadjuvant Intravesical Instillation of Mitomycin C in Treating High-risk NMIBC Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Non-Muscle-Invasive Bladder Cancer (NMIBC)
Keywords: high-risk non-muscle-invasive bladder cancer
neoadjuvant intravesical instillation
mitomycin C
en-bloc surgery
Lead sponsor: Tongji Hospital
Sponsor class: OTHER
First posted: 2024-11-20
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This was a double-blind, parallel-group, placebo-controlled, multicenter, prospective, randomized controlled Phase III clinical trial
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: 1-year recurrence-free survival rate
timeFrame: One year after randomization
Secondary outcomes:
measure: Progression free survival
timeFrame: 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.
measure: overall survival
timeFrame: up to 5 years after the end of the study.
measure: Health-related quality of life
timeFrame: up to One year after discharge
measure: Adverse event
timeFrame: up to Eight weeks after discharge
Other outcomes:
Locations:
city: Wuhan
country: China
facility: The central Hospital of wuhan
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Xiangyang
country: China
facility: Xiangyang Central Hospital
state: Hubei
Study officials:
References: