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

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.

Study Overview

• Status: Recruiting
• Conditions: Bladder Cancer
• Intervention / Treatment: Drug: Mitomycin-c 40mg/20ml and Gemcitabine 2000mg/50ml

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 82
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ho Kyung Seo, MD; Phone Number: 82-31-920-1678; Email: seohk@ncc.re.kr
• Study Contact Backup: Name: Eui Hyun Jung, Ph.D; Phone Number: 82-31-920-2451; Email: jeh0315@ncc.re.kr

Study Locations

• Korea, Republic of
  • Goyang-si, Korea, Republic of
    • Recruiting
    • National Cancer Center
    • Principal Investigator: Ho Kyung Seo, MD
    • Contact: Ho Kyung Seo; Phone Number: 82-31-920-1678; Email: seohk@ncc.re.kr
    • Sub-Investigator: Eui Hyun Jung, Ph.D

Participation Criteria

Eligibility Criteria

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

Description

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. Patients with histological confirmation of high-risk non-muscle infiltration (T1, high-grade Ta and/or CIS) bladder transition cell cancer. However, according to the definition of EAU guidelines high-risk NMIBC, Ta, low grade, and multiple recurrences of more than 3 cm are included.
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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group; Intravesical sequential treatment of Mitomycin-c 40mg/20ml and Gemcitabine 2000mg/50ml	Drug: Mitomycin-c 40mg/20ml and Gemcitabine 2000mg/50ml; Intravesical sequential treatment of Mitomycin-c 40mg/20ml and Gemcitabine 2000mg/50ml.; Other Names: Sequential treatment group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrent free survival in sequential treatment group.	Defined as the time when bladder cancer recurrence was first confirmed by biopsy at the initial TURBT date*, the time of disease progression (see PFS definition), the time of radical bladder resection, the time of bladder cancer metastasis, or the time of bladder cancer death.	1year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival in sequential treatment group.	defined as the period from the initial TURBT date* to the time when T stage progresses (e.g., Ta>T1, CIS>T1) (PFS1) or muscle invasive bladder cancer (T2 or higher) was first biopsy confirmed (PFS2) or imagingally diagnosed with metastasis to bladder cancer.	1year
Cystectomy free survival in sequential treatment group.	Defined as the period from the initial TURBT date* to the time when radical cystomy was performed.	1year
cancer specific survival in sequential treatment group.	Duration from initial TURBT date* to the time of death from bladder cancer	1year
Overall survival in sequential treatment group.	The period from the initial TURBT date* to the point of death (regardless of cause)	1year
Safety of sequential treatment.	The first safety analysis is conducted on test subjects who have developed toxicity in accordance with CTCAE standards. In particular, urinary disorders such as urinary tract infections and acute urination that occurred after injection of drugs into the bladder are evaluated.	2year

Collaborators and Investigators

• Sponsor: National Cancer Center, Korea
• Investigators: Principal Investigator: Ho Kyung Seo, MD, National Cancer Center, Korea

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2024
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: April 24, 2024
• First Submitted That Met QC Criteria: April 24, 2024
• First Posted (Actual): April 29, 2024

Study Record Updates

• Last Update Posted (Actual): April 29, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Intravesical treatment; Sequential treatment; high risks non-muscle invasive bladder cancer; Mitomycin-c; Gemcitanine
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder Neoplasms; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Alkylating Agents; Antibiotics, Antineoplastic; Mitomycins; Mitomycin; Gemcitabine
• Other Study ID Numbers: NCC2024-0026

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