The Effectiveness and Safety of Intravesical Gemcitabine Instillation to Prevent Intravesical Recurrence

Study Overview
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Brief Summary
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The aim of this study is to evaluate the effectiveness and safety of intravesical gemcitabine instillation during operation to prevent intravesical recurrence after radical nephroureterectomy in upper urinary tract urothelial carcinoma.

Detailed Description
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Study Design: Intervention Model: Single Group Assignment Masking: Open Label Primary Outcome Measures: Two year recurrence-free survival in intravesical 2000mg/52.6ml gemcitabine instillation group and control group. Secondary Outcome Measures: Time to recurrence in intravesical 2000mg/52.6ml gemcitabine instillation group and control group. Overall survival in intravesical 2000mg/52.6ml gemcitabine instillation group and control group. Safety of intravesical 2000mg/52.6ml gemcitabine instillation.

Official Title
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The Effectiveness and Safety of Intravesical Gemcitabine Instillation During Operation to Prevent Intravesical Recurrence After Radical Nephroureterectomy in Upper Urinary Tract Urothelial Carcinoma: Prospective, Phase II Study

Conditions
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Urothelial Carcinoma

Intervention / Treatment
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* Drug: Intravesical 2000mg/52.6ml gemcitabine instillation
* Other: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subjects who will undergo nephroureterectomy due to ureter or renal pelvis urothelial carcinoma Male or female aged 18 or over 18 years and not more than 85 years who were diagnosed as upper urinary tract urothelial carcinoma Normal bone marrow function: Hemoglobin >10 g/dL, ANC >1,500/mm3, platelet count>100,000/mm3 Normal bladder volume and function Normal liver function: Bilirubin ≤ 1.5 times of upper normal limit AST/ALT ≤ 1.8 times of upper normal limit Alkaline phosphatase ≤ 1.8 times of upper normal limit Subjects who voluntarily decided to participate and signed the written informed consent Exclusion Criteria: Concomitant bladder cancer Subjects who underwent any treatment due to bladder cancer within 3 years Prior hypersensitivity reaction history to gemcitabine Neurogenic bladder Subjects who underwent chemotherapy due to any cancer within 6 months Subjects who underwent neoadjuvant chemotherapy due to ureter or renal pelvis urothelial carcinoma Hypersensitivity to gemcitabine or component of gemcitabine In case of co-administration of gemcitabine and cisplatin in severe renal failure patients Moderate to severe liver dysfunction or renal dysfunction (Glomerular filtration rate < 30 mL/min) Severe bone marrow suppression Severe infection Female who are pregnant or has a possibility of pregnancy Nursing female Interstitial pneumonia or pulmonary fibrosis which is evident on chest x-ray and symptomatic Subjects who are undergoing radiotherapy on chest

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 84 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Normal saline<br>Intravesical 52.6ml normal saline instillation during radical nephroureterectomy followed by normal saline bladder irrigation | Other: Normal saline<br>* Intravesical 52.6ml normal saline instillation after radical nephroureterectomy in upper urinary tract urothelial carcinoma<br>|
| Experimental: Gemcitabine<br>Intravesical 2000mg/52.6ml gemcitabine instillation during radical nephroureterectomy followed by normal saline bladder irrigation | Drug: Intravesical 2000mg/52.6ml gemcitabine instillation<br>* Intravesical 2000mg/52.6ml gemcitabine instillation during operation to prevent intravesical recurrence after radical nephroureterectomy in upper urinary tract urothelial carcinoma<br>* Other names: Gem Tan inj (liquid);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Two year recurrence-free survival in intravesical 2000mg/52.6ml gemcitabine instillation group and control group. The recurrence will be assessed by CT scan and cystoscopic exam. | Analysis of recurrence status at 2 years from intravesical instillation of 2000mg/52.6ml gemcitabine | Two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to recurrence in intravesical 2000mg/52.6ml gemcitabine instillation group and control group. The recurrence will be assessed by CT scan and cystoscopic exam. | Analysis of time from starting intravesical instillation of 2000mg/52.6ml gemcitabine to recurrence | six years | 
| Overall survival in intravesical 2000mg/52.6ml gemcitabine instillation group and control group. | Analysis of survival status due to any cause at six years from intravesical instillation of 2000mg/52.6ml gemcitabine | six years | 
| CT cystography finding at one week after surgery. | Evaluation of leakage at CT cystography at one week from intravesical instillation of 2000mg/52.6ml gemcitabine | one week | 
| International Prostate Symptom Score questionnaire at one week after surgery. | Evaluation of survey with International Prostate Symptom Score questionnaire a one week after surgery | one week |