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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Urothelial Carcinoma
• Intervention / Treatment: Other: Normal saline; Drug: Intravesical 2000mg/52.6ml gemcitabine instillation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 134
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ho Kyung Seo, M.D.; Phone Number: 82-31-920-1678; Email: seohk@ncc.re.kr
• Study Contact Backup: Name: Yoon Seok Suh, M.D.; Phone Number: 82-10-5019-9807; Email: 12754@ncc.re.kr

Study Locations

• Korea, Republic of
  • Goyang, Korea, Republic of
    • Recruiting
    • National Cancer Center
    • Contact: Ho Kyung Seo, M.D.
    • Sub-Investigator: Jinsoo Chung, M.D.
    • Sub-Investigator: Sung Han Kim, M.D.
  • Seoul, Korea, Republic of
    • Recruiting
    • Asan Medical Center
    • Contact: Bum Sik Hong, M.D.
  • Seoul, Korea, Republic of
    • Recruiting
    • Seoul National University Hospital
    • Contact: Ja Hyun Ku, M.D.
  • Seoul, Korea, Republic of
    • Recruiting
    • Samsung Medical Center
    • Contact: Byong Chang Jeong, M.D.
  • Seoul, Korea, Republic of
    • Recruiting
    • Korea University Anam Hospital
    • Contact: Seok Ho Kang, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 84 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Cancer Center, Korea
• Collaborators: Samsung Medical Center; Asan Medical Center; Seoul National University Hospital; Korea University Anam Hospital; Chong Kun Dang Pharmaceutical Corp.
• Investigators: Principal Investigator: Seok Ho Kang, M.D., Korea universitiy

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2018
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: February 15, 2017
• First Submitted That Met QC Criteria: February 22, 2017
• First Posted (Actual): February 23, 2017

Study Record Updates

• Last Update Posted (Actual): April 14, 2022
• Last Update Submitted That Met QC Criteria: April 6, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; Carcinoma; Recurrence; Carcinoma, Transitional Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine
• Other Study ID Numbers: InstiGem

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

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