Trial of Mitomycin C During Nephroureterectomy for Urothelial Carcinoma

A Single Arm Phase II Trial of the Intraoperative Intravesical Instillation of Mitomycin C During Nephroureterectomy for Urothelial Carcinoma of the Upper Urinary Tract

Results of previous studies suggest that the timing of intravesical mitomycin C administration may impact bladder tumor recurrence rate following radical nephroureterectomy. This is the first study of its kind to attempt to identify the importance of timing of mitomycin C administration relative to bladder tumor recurrence rate following radical nephroureterectomy.This study will investigate the one year bladder tumor recurrence rate in patients with urothelial carcinoma of the upper urinary tract following intraoperative administration of mitomycin C during a nephroureterectomy, as well as the time to bladder tumor recurrence in this patient population.

Study Overview

• Status: Completed
• Conditions: Urothelial Carcinoma
• Intervention / Treatment: Drug: Mitomycin c

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32608
      • University of Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Both males and females ≥ eighteen years of age
• Clinical diagnosis of urothelial carcinoma of the renal pelvis and/or ureter. Clinical diagnosis of urothelial carcinoma may be based upon radiographic, pathologic or cytological findings alone or in combination with one another. No other histology is allowed.
• The TNM stage of the subject's disease (using the American Joint Committee on Cancer [AJCC] Cancer Staging Manual, 8th Edition) must be Tis, Ta, T1, T2, or T3, N0, M0. Subjects may have either a high-grade or low-grade tumor.
• ECOG performance status of 0-2
• Written informed consent obtained from the subject and the ability for the subject to comply with all the study-related procedures.
• Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy prior to and for at least 3 months after mitomycin C instillation to minimize the risk of pregnancy. Prior to study enrollment, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy.
• Males with female partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) should avoid conceiving children prior to and for 3 months following mitomycin C instillation
• Subjects must have hemoglobin ≥ 9 g/dL and a platelet count ≥ 100,000/μL.

Exclusion Criteria:

• Active urothelial carcinoma of the bladder within 12 months prior to enrollment
• History of adverse reaction to mitomycin C
• Evidence of regional or metastatic disease.
• History of radical cystectomy
• Planned radical cystectomy at the time of nephroureterectomy
• Females or males of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy prior to and for at least 3 months after mitomycin C instillation.
• Females who are pregnant or breastfeeding.
• History of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician.
• Prisoners or subjects who are involuntarily incarcerated.
• Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness.
• Subjects demonstrating an inability to comply with the study and/or follow-up procedures

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: Mitomycin C	Drug: Mitomycin c; All participants will receive a single 40 mg dose of mitomycin C intraoperatively during their scheduled nephroureterectomy. This single dose will be given through a catheter in the subject's bladder.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bladder Tumor Recurrence Rate	The bladder tumor recurrence rate will be measured by the percentage of subjects who are confirmed by bladder biopsy to have a recurrence of urothelial carcinoma in the bladder following nephroureterectomy	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Bladder Tumor Recurrence	The time to bladder tumor recurrence will be characterized using Kapalan-Meier plots.	3 years
Bladder Tumor Recurrence Rate	The bladder tumor recurrence rate will be measured by the proportion of subjects who are confirmed by bladder biopsy to have a recurrence of urothelial carcinoma in the bladder following nephroureterectomy	3 years

Collaborators and Investigators

• Sponsor: University of Florida
• Investigators: Principal Investigator: Paul Crispen, MD, University of Florida

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2018
• Primary Completion (Actual): November 10, 2021
• Study Completion (Actual): December 14, 2023

Study Registration Dates

• First Submitted: August 31, 2018
• First Submitted That Met QC Criteria: August 31, 2018
• First Posted (Actual): September 5, 2018

Study Record Updates

• Last Update Posted (Estimated): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 2, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Transitional Cell; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Alkylating Agents; Antibiotics, Antineoplastic; Mitomycins; Mitomycin
• Other Study ID Numbers: UF-GU-001; OCR18677 (Other Identifier: University of Florida); IRB201802090 (Other Identifier: University of Florida)

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No