The Clinical Effectiveness and Safety of Intravesical Mitomycin-C and Gemcitabine Sequential Therapy

A Study to Assess the Clinical Effectiveness and Safety of Intravesical Mitomycin-C and Gemcitabine Sequential Therapy in Patients With High Risk Non-muscle Invasive Bladder Cancer (NMIBC) Unresponsive to BCG Therapy

The aim of this study is to evaluate the effectiveness and safety of mitomycin-c and gemcitabine sequential instillation in BCG unresponsive high risk non-muscle invasive bladder cancer patients.

Phase 2 clinical, multi-institutional, open assignment prospective study

Primary Outcome Measures:

1-year recurrence-free survival period in high-risk groups after sequential injection of Mitomycin-c 40 mg/20 ml and Gemcitabine 2000 mg/50 ml in non-muscle invasive bladder cancer patients in BCG-free high-risk groups.

Secondary Outcome Measures:

Progression Free Survival (PFS), Cystectomy free survival (CFS), Cancer specific survival (CSS), Overall survival (OS) and safety after Mitomycin-c 40mg/20ml and Gemcitabine 2000mg/50ml treatment in non-muscle invasive bladder cancer patients in BCG-free high-risk groups.

Inclusion Criteria:

1. a patient over the age of 20
2. Patients who are willing and able to complete a written test subject consent/approval for this examination.
3. Histologically confirmed high-risk NMIBC (according to AUA guidelines; High-grade T1 disease, any recurrent high-grade Ta, high-grade Ta >3 cm, high-grade Ta that is multifocal, any carcinoma in situ, any BCG failure in high-grade patients, any variant histology, any lymphovascular invasion, and any high-grade prostatic urethral involvement) with prior BCG therapy.
4. The most recent bladder examination/TURBT must be performed within 8 weeks before the initial administration of the trial treatment. Patients with high risk NMIBC who received proper BCG treatment but did not respond to BCG
5. Patients who are not eligible for a radical bladder resection or who have refused surgery.
6. Patient who are not being pregnant or breast feeding until the study period.

Exclusion Criteria:

1. Patient diagnosed with muscle-invasive bladder cancer at TURBT
2. If upper urinary tract urothelial cancer is accompanied by imaging
3. If the imaging indicates extravesical involvement (cT3)
4. Imaging shows lymph node metastasis (short-axis 15mm or more) or distant metastasis
5. In a biopsy, non-transitional cell histology is dominant, or only non-transitional cell tissue is present (primary squamous cell carcinoma, primary adenocarcinoma, small cell carcinoma, sarcoma, carcinosarcoma, paraganglioma, melanoma, lymphoma)
6. In the case of receiving systemic cytotoxic chemotherapy for other cancers within 3 years
7. If patient have a history of pelvic radiation therapy for other cancers within 3 years
8. If patient have a history of receiving Mitomycin-c or gemcitabine in the bladder within 3 years. The exception is cases used for the purpose of injection therapy of anticancer drugs in the early bladder cancer
9. If patient has a history of allergy to mitomycin-c or gemcitabine
10. Cystoscopy shows a tumor in the prostate urethra
11. Patients who have participated in studies using clinical trial drugs and are currently receiving clinical trial drugs or who have used clinical trial drugs or clinical trial medical devices within 4 weeks prior to the date of initial treatment
12. After post-cystoscopy/TURBT, the patient received intravesical chemotherapy prior to the start of trial treatment
13. Thrombocytopenia, coagulopathy or bleeding tendency patient.
14. Pregnant or breast-feeding women
15. If patient treated yellow fever vaccine or phenytoin
16. Dysfunction of liver or kidney (GFP≤30)
17. If patient undergo severe myelosuppression
18. If patient complicated severe infection
19. If patient definitely diagnosed interstitial lung disease or lung fibrosis by chest X-ray.
20. If patient conduct chest radiotherapy.