A Phase 3 Study of UGN-102 for Low-Grade Intermediate-Risk Non-Muscle Invasive Bladder Cancer
- Conditions
- Bladder CancerUrothelial CarcinomaUrothelial Carcinoma Bladder
- Interventions
- Procedure: TURBT
- Registration Number
- NCT04688931
- Lead Sponsor
- UroGen Pharma Ltd.
- Brief Summary
This global, randomized, controlled, open-label Phase 3 study was designed to assess the long-term efficacy and safety of UGN-102 (mitomycin) for intravesical solution with or without (±) transurethral resection of bladder tumors (TURBT) versus TURBT alone for the treatment of patients with low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC).
- Detailed Description
Eligible patients were randomized in a 1:1 ratio to UGN-102 ± TURBT or TURBT alone. Randomization was stratified by the presence of a previous LG-NMIBC episode within 1 year of the current diagnosis (yes or no). Starting on Day 1, patients randomized to the UGN-102 ± TURBT arm will receive 6 weekly intravesical instillations of UGN-102 and patients randomized to the TURBT alone arm underwent TURBT.
All patients returned to the clinic approximately 3 months after the start of treatment for a disease assessment visit. Response to treatment was determined based on visual observation (white light cystoscopy), histopathology of any remaining or new lesions, and voiding urine cytology. Patients confirmed to have a complete response (CR), defined as having no detectable disease (NDD) in the bladder, received no further treatment and entered the Follow-up Period of the study. Patients confirmed to have a non-complete response (NCR) due to residual LG disease in either treatment arm underwent TURBT of any remaining lesions and then entered the Follow-up Period of the study.
During the Follow-up Period, patients returned to the clinic every 3 months to determine if they remained disease free. Patients remained on study until completion of all follow-up visits or until disease recurrence, disease progression, or death was documented, whichever occurred first. Patients determined to have a protocol-defined recurrence or progression at any follow-up or unscheduled visit were considered to have completed the study and released to the care of their treating physician.
Study enrollment was stopped early by the sponsor to pursue an alternative development strategy for UGN-102 in the treatment of bladder cancer. Patients who had consented at the time the trial terminated were permitted to continue, but follow-up was terminated once the last patient had been followed for 15 months after the start of treatment.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 282
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Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
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Patient who has newly diagnosed or historic LG-NMIBC (Ta) histologically confirmed by cold cup biopsy at Screening or within 8 weeks of Screening.
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Has intermediate risk disease, defined as having 1 or 2 of the following:
- Presence of multiple tumors;
- Solitary tumor > 3 cm;
- Recurrence (≥ 1 occurrence of LG-NMIBC within 1 year of the current diagnosis).
-
Negative voiding cytology for HG disease within 6 weeks of Screening.
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Has adequate organ and bone marrow function as determined by the following routine laboratory tests:
- Leukocytes ≥ 3,000 cells per μL;
- Absolute neutrophil count ≥ 1,500 cells per μL;
- Platelets ≥ 100,000 per μL;
- Hemoglobin ≥ 9.0 g/dL;
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN);
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN;
- Alkaline phosphatase (ALP) ≤ 2.5 × ULN;
- Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min.
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Has no evidence of active urinary tract infection (UTI).
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Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for clinical study participants. Women of childbearing potential (defined as premenopausal women who have not been sterilized), including female patients and female partners of male patients, must be willing to use 2 acceptable forms of effective contraception from enrollment through 6 months post-treatment.
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History of carcinoma in situ (CIS) on preliminary cystoscopy within 5 years of enrollment.
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Received Bacillus Calmette-Guérin (BCG) treatment for urothelial carcinoma (UC) within previous 1 year.
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History of HG papillary UC in the past 2 years.
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Known allergy or sensitivity to mitomycin that in the investigator's opinion cannot be readily managed.
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Clinically significant urethral stricture that would preclude passage of a urethral catheter.
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History of pelvic radiotherapy.
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History of:
- Neurogenic bladder;
- Active urinary retention;
- Any other condition that would prohibit normal voiding.
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Past or current muscle invasive (ie, T2, T3, T4) or metastatic UC or concurrent upper tract UC.
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Current tumor stage of T1.
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Has an underlying substance abuse or psychiatric disorder such that, in the opinion of the investigator, the patient would be unable to comply with the protocol.
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History of prior treatment with an intravesical chemotherapeutic agent except for a single dose of chemotherapy immediately after any previous TURBT.
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Has previously participated in a study in which they received UGN-102.
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Has participated in a study with an investigational agent or device within 30 days of randomization.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description TURBT Alone TURBT TURBT on Day 1 + repeat TURBT for patients with NCR due to residual LG disease at the 3-month Visit (3 months after the initial TURBT). UGN-102 ± TURBT TURBT 6 weekly intravesical instillations of UGN-102 (75 mg mitomycin) starting on Day 1 + TURBT for patients with NCR due to residual LG disease at the 3-month Visit (3 months after the start of treatment with UGN-102). UGN-102 ± TURBT UGN-102 6 weekly intravesical instillations of UGN-102 (75 mg mitomycin) starting on Day 1 + TURBT for patients with NCR due to residual LG disease at the 3-month Visit (3 months after the start of treatment with UGN-102).
- Primary Outcome Measures
Name Time Method Disease-free Survival (DFS) 15 months DFS is defined as the time from randomization until the earliest date of any of the following events: failure to be rendered free of local disease at the 3-month Visit (TURBT arm only), recurrence of LG disease after the 3-month Visit (ie, during the Follow-up Period), progression to high-grade (HG) disease, or death due to any cause. Summarized is the Kaplan-Meier estimated probability of remaining event-free at 15 months from randomization.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) 12 months DOR is defined as the time from first documented CR until the earliest date of recurrence of LG disease, progression to HG disease, or death due to any cause. DOR applies only to patients who achieve CR at the 3-month Visit. Summarized is the Kaplan-Meier estimated probability of remaining in response at 12 months after 3-month CR.
Number of TURBTs 3 months Number of TURBTs is defined as the average number of per protocol TURBTs per patient in each arm. Per protocol TURBTs are defined as the Day 1 TURBT for patients in the TURBT alone arm and TURBT due to residual LG disease at the 3-month disease assessment in either arm.
Number of Participants With Post-baseline PCS Serum Chemistry Values Up to 6 months The number of patients with each type of event will be summarized.
Time to Recurrence (TTR) 15 months TTR is defined as the time from randomization until the earliest date of any of the following events: failure to be rendered free of local disease at the 3-month Visit (TURBT arm only), recurrence of LG disease after the 3-month Visit (ie, during the Follow-up Period), or progression to HG disease. Summarized is the Kaplan-Meier estimated probability of remaining event-free at 15 months from randomization.
Complete Response Rate (CRR) 3 months CRR is defined as the percentage of patients who achieve CR at the 3-month Visit.
Changes From Baseline in Health-related Quality of Life Pre-treatment to 3 months after the start of treatment The European Organisation for Research and Treatment of Cancer (EORTC) 24-item quality of life questionnaire for patients with NMIBC (QLQ-NMIBC24) is a patient-reported instrument that assesses 11 domains (urinary symptoms, malaise, future worries, bloating and flatulence, intravesical treatment issues, sexual intimacy, risk of contaminating partner, male sexual problems, female sexual problems, sexual function, and sexual enjoyment).
All of the domains range in score from 0 to 100 with lower scores reflecting better functioning/quality of life and higher scores reflecting worse functioning/quality of life.
Summarized is the change from baseline in domain scores at the 3-month Visit. Changes in domain scores were calculated for patients with non-missing answers at both time points.Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Hematology Values Up to 6 months The number of patients with each type of event will be summarized.
Observed CRR at Scheduled Disease Assessment Time Points 12 months Observed CRR at scheduled disease assessment time points is defined as the percentage of patients who achieve CR at the 3-month Visit and maintain CR up to a particular follow-up visit. Summarized is the observed percentage of patients remaining in response at 3, 6, 9, and 12 months after 3-month CR.
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs of Special Interest Up to 21 months The number of patients with each type of event will be summarized. TEAEs were defined as adverse events (AEs) that occurred on or after the day of first instillation of UGN-102 for patients in the UGN-102 ± TURBT arm or the day of initial TURBT for patients in the TURBT alone arm, or pre-treatment events that worsened during the study.
Trial Locations
- Locations (137)
Arizona Institute of Urology, PLLC
🇺🇸Tucson, Arizona, United States
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
Urology Group of Southern California
🇺🇸Los Angeles, California, United States
San Diego Clinical Trials
🇺🇸San Diego, California, United States
Providence Saint John's Health Center
🇺🇸Santa Monica, California, United States
Skyline Urology
🇺🇸Sherman Oaks, California, United States
University of Chicago Hospital
🇺🇸Chicago, Illinois, United States
Comprehensive Urologic Care
🇺🇸Lake Barrington, Illinois, United States
First Urology, PSC
🇺🇸Jeffersonville, Indiana, United States
Wichita Urology Group
🇺🇸Wichita, Kansas, United States
Scroll for more (127 remaining)Arizona Institute of Urology, PLLC🇺🇸Tucson, Arizona, United States