Clinical trial NCT04006691: Efficacy and Safety of UGN-101 in Recurrent Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Carcinoma
Transitional Cell Carcinoma
Transitional Cell Cancer of the Renal Pelvis and Ureter
Keywords: 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
Lead sponsor: UroGen Pharma Ltd.
Sponsor class: INDUSTRY
First posted: 2019-07-05
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Main Inclusion Criteria:

1. Patients with recurrent LG UTUC who were found to be CR at the PDE 1 Visit (in Trial TC-UT-03).
2. 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.
3. Urine wash cytology sampled from the UUT documenting the absence of HG urothelial cancer.
4. Patients must have adequate organ and bone marrow function as determined by routine laboratory tests.
5. Patient has no active urinary tract infection (UTI) as confirmed by urine culture or urinalysis

Main Exclusion Criteria:

1. Patient intends to be treated with systemic chemotherapy during the duration of the trial.
2. Patient with urinary obstruction.
3. Inability to deliver the IP to the UUT.
4. 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.
5. Patient has a contraindication to mitomycin treatment, or known sensitivity to mitomycin.

Primary outcomes:
measure: Complete response (CR) rate
timeFrame: An average of 11 weeks
Secondary outcomes:
measure: Long-term durability of complete response (CR)
timeFrame: 3, 6, 9 and 12 months
Other outcomes:
measure: Incidence (number of patients) of adverse events
timeFrame: 15 months
measure: Frequency (number of events) of adverse events
timeFrame: 15 months
measure: Clinically meaningful changes in laboratory values of blood hematology, coagulation, liver and kidney function parameters and urinalysis
timeFrame: 15 months
measure: Clinically meaningful changes in vital signs assessments values (blood pressure, pulse and temperature)
timeFrame: 15 months
measure: Clinically meaningful changes in full physical examination values including General appearance, Cardiovascular and Respiratory system, HEENT (head, eyes, ears, nose, and throat) and neck, Abdomen Extremities, Neurologic system, Skin and Urological system
timeFrame: 15 months
Locations:
city: Los Angeles
country: United States
facility: UCLA - University of California, Los Angeles
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Baltimore
country: United States
facility: John Hopkins University
state: Maryland
city: Las Vegas
country: United States
facility: Urology Center Las Vegas
state: Nevada
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
Study officials:
affiliation: UroGen Pharma
name: Ifat Klein, Phd
role: STUDY_DIRECTOR
References: