Efficacy and Safety of UGN-101 in Recurrent Patients

Study Overview
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Brief Summary
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This trial is designed to evaluate the efficacy and safety of UGN-101 administered to the upper urinary tract (UUT) in patients who were treated in Trial TC-UT-03, found to be a complete response (CR) at the Primary Disease Evaluation (PDE) 1 Visit and are subsequently found to have a documented recurrence of low grade (LG) upper tract urothelial carcinoma (UTUC) at follow up (FU).

Detailed Description
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This is an open-label, single-arm, Phase 3b multicenter extension trial, designed to evaluate the efficacy and safety of UGN-101 administered to the UUT in patients who were treated in Trial TC-UT-03, found to be a CR at the PDE 1 Visit, and are subsequently found to have a documented recurrence of LG UTUC at FU. Upon signing of informed consent, the patients will undergo their routine ureteroscopy to assess durability. A biopsy will be performed at Visit 0, if appropriate, to confirm evidence of tumor. If a high grade (HG) UTUC is confirmed by biopsy and/or cytology, the patient will be excluded from the retreatment trial. Eligible patients with confirmed LG non-invasive UTUC will be treated with 3 to 6 once-weekly instillations of UGN-101 in a retrograde fashion, per investigator's discretion. Five weeks (± 1 week) following the last Investigational product (IP) treatment, the patient will be assessed for efficacy and safety at the PDE 2 Visit. At this visit, the patient will undergo ureteroscopy and any remaining lesions will be biopsied, and UUT urine wash will be collected for cytology. Patients demonstrating CR at the PDE 2 Visit will undergo FU visits at 3, 6, 9, and 12 months (± 2 weeks) following the PDE 2 Visit. The trial will be approximately 15 months, per patient: a 3- to 6-week treatment period, followed by 4 to 6 weeks post-treatment leading up to the PDE 2 Visit, and a 12-month FU post PDE 2 Visit. This trial will follow the Steering Committee, and a Data Monitoring Committee (DMC) has been assigned as established for the primary trial TC-UT-03.

Official Title
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A Phase 3b Multicenter Extension Trial Evaluating the Efficacy and Safety of UGN-101 (Mitomycin Gel) for Instillation on Ablation of Upper Urinary Tract Urothelial Carcinoma in Recurrent Patients From Trial TC-UT-03

Conditions
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Carcinoma, Transitional Cell Carcinoma, Transitional Cell Cancer of the Renal Pelvis and Ureter

Intervention / Treatment
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* Drug: UGN-101 instillations


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Patients with recurrent LG UTUC who were found to be CR at the PDE 1 Visit (in Trial TC-UT-03). Biopsy taken from 1 or more tumors located in the UUT shows LG urothelial carcinoma (up to 2 months before Visit 0). If there are tumors in both the kidney and the ureter, at least 1 biopsy should be taken from each location. Urine wash cytology sampled from the UUT documenting the absence of HG urothelial cancer. Patients must have adequate organ and bone marrow function as determined by routine laboratory tests. Patient has no active urinary tract infection (UTI) as confirmed by urine culture or urinalysis Main Exclusion Criteria: Patient intends to be treated with systemic chemotherapy during the duration of the trial. Patient with urinary obstruction. Inability to deliver the IP to the UUT. Patient has any other medical or mental condition(s) that make(s) their participation in the trial unadvisable in the opinion of the treating investigator. Patient has a contraindication to mitomycin treatment, or known sensitivity to mitomycin.

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: UGN-101 instillations<br>The Mitomycin C (MMC) concentration of UGN-101 to be used in this trial will be 4 mg MMC per 1 mL of TC-3 gel, the maximum dose is 15ml. 3-6 once weekly intravesical instillations for the ablation treatment. | Drug: UGN-101 instillations<br>* Treatment with UGN-101 once weekly for a total of 3-6 times; in a retrograde fashion.<br>* Other names: MitoGel™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response (CR) rate | Complete response defined dichotomously as Success if CR was confirmed at the end of the treatment period (PDE 2 Visit), and Failure otherwise. | An average of 11 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long-term durability of complete response (CR) | This endpoint is defined only for those patients demonstrating CR at the PDE 2 Visit. | 3, 6, 9 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TC-3, MitoGel, UGN-101, UTUC, Ureteral, Upper Tract, Carcinoma, Kidney, Renal, Ureter, Gel, Local, Mitomycin C, Prolonged Release, Slow Release, Kidney Sparing, T1, T0, Low Grade, Transitional Cell Carcinoma of Renal Pelvis, TCC