A Phase 3 Study of UGN-102 for Low-Grade Intermediate-Risk Non-Muscle Invasive Bladder Cancer

NCT ID: NCT04688931

Last Updated: 2024-06-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 282 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-19
• Study Completion Date: 2023-03-17

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.

Conditions

Bladder Cancer; Urothelial Carcinoma; Urothelial Carcinoma Bladder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

UGN-102 ± 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).

Group Type: EXPERIMENTAL

UGN-102

Intervention Type: DRUG

UGN-102 consists of mitomycin and sterile hydrogel (a proprietary thermally responsive gel) that is used to reconstitute mitomycin before instillation. The reverse thermal properties of UGN-102 allow for local administration of mitomycin as a liquid under chilled conditions, with subsequent conversion to a semi-solid gel depot following instillation into the bladder.

TURBT

Intervention Type: PROCEDURE

The current standard of care for treatment of LG-IR-NMIBC is TURBT under general anesthesia.

TURBT Alone

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).

Group Type: ACTIVE_COMPARATOR

TURBT

Intervention Type: PROCEDURE

The current standard of care for treatment of LG-IR-NMIBC is TURBT under general anesthesia.

Interventions

UGN-102

UGN-102 consists of mitomycin and sterile hydrogel (a proprietary thermally responsive gel) that is used to reconstitute mitomycin before instillation. The reverse thermal properties of UGN-102 allow for local administration of mitomycin as a liquid under chilled conditions, with subsequent conversion to a semi-solid gel depot following instillation into the bladder.

Intervention Type: DRUG

TURBT

The current standard of care for treatment of LG-IR-NMIBC is TURBT under general anesthesia.

Intervention Type: PROCEDURE

Other Intervention Names

UGN-102 (mitomycin) for intravesical solution; Transurethral resection of bladder tumors

Eligibility Criteria

Inclusion Criteria

1. 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.

2. Patient who has newly diagnosed or historic LG-NMIBC (Ta) histologically confirmed by cold cup biopsy at Screening or within 8 weeks of Screening.

3. 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).

4. Negative voiding cytology for HG disease within 6 weeks of Screening.

5. 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.

6. Has no evidence of active urinary tract infection (UTI).

7. 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.

Exclusion Criteria

1. History of carcinoma in situ (CIS) on preliminary cystoscopy within 5 years of enrollment.

2. Received Bacillus Calmette-Guérin (BCG) treatment for urothelial carcinoma (UC) within previous 1 year.

3. History of HG papillary UC in the past 2 years.

4. Known allergy or sensitivity to mitomycin that in the investigator's opinion cannot be readily managed.

5. Clinically significant urethral stricture that would preclude passage of a urethral catheter.

6. History of pelvic radiotherapy.

7. History of:

• Neurogenic bladder;
• Active urinary retention;
• Any other condition that would prohibit normal voiding.

8. Past or current muscle invasive (ie, T2, T3, T4) or metastatic UC or concurrent upper tract UC.

9. Current tumor stage of T1.

10. 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.

11. History of prior treatment with an intravesical chemotherapeutic agent except for a single dose of chemotherapy immediately after any previous TURBT.

12. Has previously participated in a study in which they received UGN-102.

13. Has participated in a study with an investigational agent or device within 30 days of randomization.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

UroGen Pharma Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sandip Prasad, MD

Role: PRINCIPAL_INVESTIGATOR

Atlantic Health System

Locations

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

Regional Urology, LLC

Shreveport, Louisiana, United States

Chesapeake Urology Research Associates

Baltimore, Maryland, United States

Chesapeake Urology Research Associates

Hanover, Maryland, United States

Adult & Pediatric Urology, PC

Omaha, Nebraska, United States

Urology Center

Las Vegas, Nevada, United States

New Jersey Urology

Bloomfield, New Jersey, United States

New Jersey Urology

Englewood, New Jersey, United States

Garden State Urology

Morristown, New Jersey, United States

Albany Medical Center

Albany, New York, United States

Great Lakes Physician dba WNY Urology Associates

Cheektowaga, New York, United States

AccuMed Research Associates

Garden City, New York, United States

Manhattan Medical Research

New York, New York, United States

Stony Brook Cancer Center

Stony Brook, New York, United States

Associated Medical Professionals of NY, PLLC

Syracuse, New York, United States

UNC Chapel Hill Memorial Hospital

Chapel Hill, North Carolina, United States

Clinical Research Solutions

Middleburg Heights, Ohio, United States

Centers for Advanced Urology, LLP d.b.a Mid-Atlantic Urology

Bala-Cynwyd, Pennsylvania, United States

Penn State Health Milton S. Hershey Medical Center and College of Medicine

Hershey, Pennsylvania, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Carolina Urologic Research Center

Myrtle Beach, South Carolina, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Urology San Antonio

San Antonio, Texas, United States

Multiprofile Hospital for Active Treatment "Puls", Department of Urology

Blagoevgrad, , Bulgaria

Multiprofile Hospital for Active Treatment - Blagoevgrad

Blagoevgrad, , Bulgaria

Complex Oncology Center - Burgas

Burgas, , Bulgaria

Multiprofile Hospital for Active Treatment "Dr. Tota Venkova", Gabrovo, Department of Urology

Gabrovo, , Bulgaria

Multiprofile Hospital for Active Treatment "Sveti Nikolai Chudotvorets", Lom

Lom, , Bulgaria

Multiprofile Hospital for Active Treatment "City Clinic - Sveti Georgi"

Montana, , Bulgaria

University Multiprofile Hospital for Active Treatment "Dr. Georgi Stranski", Pleven, Urology Clinic

Pleven, , Bulgaria

University Multiprofile Hospital for Active Treatment "Sveta Marina" - Pleven, Department of Urology

Pleven, , Bulgaria

Multiprofile Hospital for Active Treatment Park Hospital

Plovdiv, , Bulgaria

University Multiprofile Hospital for Active Treatment "Sveti Georgi", Plovdiv, Clinic of Urology

Plovdiv, , Bulgaria

University Multiprofile Hospital for Active Treatment, Plovdiv, Department of Urology

Plovdiv, , Bulgaria

University Multiprofile Hospital for Active Treatment 'Kanev', Ruse, Department of Urology

Rousse, , Bulgaria

Multiprofile Hospital for Active Treatment - Shumen, Shumen, Department of Urology

Shumen, , Bulgaria

University Multiprofile Hospital for Active Treatment "Aleksandrovska", Sofia, Urology Clinic

Sofia, , Bulgaria

University Multiprofile Hospital for Active Treatment and Emergency Medicine "N.I. Pirogov", Sofia, Urology Clinic

Sofia, , Bulgaria

Multiprofile Hospital for Active Treatment - Targovishte

Targovishte, , Bulgaria

Multiprofile Hospital for Active Treatment, Varna part of Military Medical Academy, Clinic of Urology

Varna, , Bulgaria

Multiprofile Hospital for Active Treatment "Sveta Anna", Varna, Urology Clinic

Varna, , Bulgaria

University Multiprofile Hospital for Active Treatment "Sveta Marina"

Varna, , Bulgaria

Multiprofile Regional Hospital for Active Treatment "Dr. Stefan Cherkezov", Veliko Tarnovo, Department of Urology

Veliko Tarnovo, , Bulgaria

First Private Hospital Vratsa, Department of Urology

Vratsa, , Bulgaria

Multiprofile Hospital for Active Treatment "Sveti Pantaleymon", Yambol, Department of Urology

Yambol, , Bulgaria

East Viru Central Hospital, Surgery Clinic

Kohtla-Järve, , Estonia

East Tallinn Central Hospital Ltd., Surgery Clinic, Centre of Urology

Tallinn, , Estonia

West Tallinn Central Hospital Ltd., Department of Urology

Tallinn, , Estonia

North Estonia Medical Centre Foundation Ltd., Surgery Clinic, General and Oncology Urology Centre

Tallinn, , Estonia

Tartu University Hospital, Surgery Clinic, Department of Urology and Kidney Transplantation

Tartu, , Estonia

LTD Central University Clinic After Academic N. Kipshidze

Tbilisi, , Georgia

JSC Jerarsi, Department of Urology

Tbilisi, , Georgia

LTD Acad. F. Todua Medical Center - LTD Research Institute of Clinical Medicine, Clinical Research Department

Tbilisi, , Georgia

LTD Gidmedi, Urology Department

Tbilisi, , Georgia

LTD L. Managadze National Center of Urology, Department of Urology

Tbilisi, , Georgia

LTD MMT Hospital, Urology Department

Tbilisi, , Georgia

Malkhaz Katsiashvili Multiprofile Emergency Medicine Center LTD, Department of Urology

Tbilisi, , Georgia

Pineo Medical Ecosystem Ltd., Department of Urology

Tbilisi, , Georgia

Tbilisi State Medical University and Ingorokva High Technology Medical Center University Clinic LTD, Urology Department

Tbilisi, , Georgia

Rambam Health Care Campus

Haifa, , Israel

Lady Davis Carmel Medical Center

Haifa, , Israel

Edith Wolfson Medical Center

Holon, , Israel

Rabin Medical Center

Petah Tikva, , Israel

Chaim Sheba Medical Center

Ramat Gan, , Israel

Liepajas Regional Hospital, Urology Department

Liepāja, , Latvia

P. Stradins Clinical University Hospital, Center for Urology

Riga, , Latvia

LLC Riga East University Hospital, Clinic of Urology and Oncologic Urology

Riga, , Latvia

Daugavpils Regional Hospital, Urology Department

Riga, , Latvia

Jan Biziel University Hospital #2 in Bydgoszcz, Teaching Department of Urology

Bydgoszcz, , Poland

AKMED

Gliwice, , Poland

Prof.E Michalowski Specialist Hospital

Katowice, , Poland

SCM sp. z o.o. (LLC)

Krakow, , Poland

"City Clinic" Limited Liability Company

Warsaw, , Poland

Miedzyleski Specialist Hospital in Warsaw, Department of Urology

Warsaw, , Poland

Krasnoyarsk A.I. Kryzhanovsky Regional Oncology Center

Krasnoyarsk, , Russia

D.D. Pletnyov City Clinical Hospital, Department of Oncourology

Moscow, , Russia

Moscow City Oncology Hospital #62

Moscow, , Russia

Murmansk Bayandin Regional Clinical Hospital

Murmansk, , Russia

Privolzhsky Regional Medical Center, Urology Department

Nizhny Novgorod, , Russia

Tsyb Medical Radiology Research Center, Oncourology Department

Obninsk, , Russia

Clinical Oncology Center, Department of Urology and Oncology

Omsk, , Russia

N.N. Burdenko Penza Regional Clinical Hospital, Department of Urology

Penza, , Russia

Pyatigorsk City Clinical Hospital, Department of Urology

Pyatigorsk, , Russia

Leningrad Regional Clinical Oncology Center, Department of Chemotherapy

Saint Petersburg, , Russia

Aleksandrovskaya City Hospital, Department of Urology

Saint Petersburg, , Russia

St. Petersburg Clinical Hospital under the Russian Academy of Sciences, Department of Urology

Saint Petersburg, , Russia

A.M. Nikiforov Russian Center for Emergency and Radiology Medicine, Department of Urology

Saint Petersburg, , Russia

St. Luka Clinical Hospital, Department of Urology

Saint Petersburg, , Russia

St.-Petersburg Scientific Research Institute of Phthisiopulmonology

Saint Petersburg, , Russia

Medical and Sanitary Unit #70 of "Passazhiravtotrans"

Saint Petersburg, , Russia

I.I. Mechnikov North-Western State Medical University, Department of Urology

Saint Petersburg, , Russia

Railway Clinical Hospital under OAO Russian Railways

Saint Petersburg, , Russia

First I.P. Pavlov State Medical University of St. Petersburg

Saint Petersburg, , Russia

N.N. Petrov National Medical Research Center of Oncology, Oncourology Department

Saint Petersburg, , Russia

City Hospital #15, Urology Department #12

Saint Petersburg, , Russia

Siberian State Medical University

Tomsk, , Russia

Regional Oncology Center, Tyumen, Oncology Department

Tyumen, , Russia

Republican Clinical Oncology Center

Ufa, , Russia

Volgograd Regional Center for Urology and Nephrology, Urology Department

Volzhskiy, , Russia

Medical Center for Diagnostics and Prevention Plus

Yaroslavl, , Russia

Sverdlovsk Regional Clinical Hospital #1

Yekaterinburg, , Russia

Clinical Center of Serbia, Clinic of Urology

Belgrade, , Serbia

Clinical Hospital Center Bezanijska Kosa, Clinic of Surgery, Department of Urology

Belgrade, , Serbia

Clinical Hospital Center Zemun, Urology unit

Belgrade, , Serbia

Clinical Center Kragujevac, Clinic of Urology, Nephrology and Dialysis

Kragujevac, , Serbia

Chernihiv Medical Center of Modern Oncology

Chernihiv, , Ukraine

Regional Communal Noncommercial Enterprise: Chernivtsi Regional Clinical Hospital

Chernivtsi, , Ukraine

Regional Municipal Non-commercial Enterprise "Chernivtsi Emergency Medical Hospital", Urology Department

Chernivtsi, , Ukraine

Public Enterprise "Dnipropetrovsk I.I. Mechnikov Regional Clinical Hospital" under Dnipropetrovsk Regional Council, Urology Department #2

Dnipro, , Ukraine

Public Non-Profit Enterprise "City Clinical Hospital #6" under Dnipro City Council, Department of Urology

Dnipro, , Ukraine

Public Non-Profit Enterprise "City Clinical Hospital #4" under Dnipro City Council, Department of Geriatric Urology Care

Dnipro, , Ukraine

Public Non-Profit Enterprise "Regional Clinical Hospital under Ivano-Frankivsk Regional Council", Department of Urology

Ivano-Frankivsk, , Ukraine

Prykarpattia Clinical Oncology Center under Ivano-Frankivsk Regional Council

Ivano-Frankivsk, , Ukraine

Public Non-Profit Enterprise under Kharkiv Regional Council "V.I. Shapoval Regional Medical Clinical Center for Urology and Nephrology", Urology Department #5

Kharkiv, , Ukraine

Communal Non-Profit Enterprise "Regional Center of Oncology", Department of Oncourology

Kharkiv, , Ukraine

Public Non-Profit Enterprise under Kharkiv Regional Council "Regional Clinical Specialized Center for Radiation Protection of Population", Department of Surgery

Kharkiv, , Ukraine

Communal non-commercial enterprise of Kherson regional council "Kherson regional oncological dispensary"

Kherson, , Ukraine

State Institution: Institute of Urology under the National Academy of Medical Sciences of Ukraine

Kyiv, , Ukraine

Volyn Regional Medical Oncology Centre

Lutsk, , Ukraine

Communal Noncommercial Enterprise of Lviv Regional Council "Lviv Regional Clinical Hospital", Department of Urology

Lviv, , Ukraine

Public Non-profit Enterprise under Lviv Regional Council: Lviv Regional Treatment and Diagnostics Oncology Center

Lviv, , Ukraine

Municipal Non-Profit Enterprise "Lviv Clinical Emergency Care Hospital", Department of Urology

Lviv, , Ukraine

Public Non-Profit Enterprise "Odesa Regional Clinical Hospital" under Odesa Regional Council

Odesa, , Ukraine

Public Non-Profit Enterprise "City Clinical Hospital #10" under Odesa City Council, Department of Urology and Nephrology

Odesa, , Ukraine

Sumy Regional Clinical Oncology Center

Sumy, , Ukraine

Public Non-Profit Enterprise Ternopil Regional Clinical Oncology Center, Department of Chemotherapy

Ternopil, , Ukraine

Municipal non-profit enterprise "Transcarpathian antitumor center" of the Transcarpathian Regional Council

Uzhhorod, , Ukraine

Communal Nonprofit Enterprise "Podilsky Regional Center of Oncology of Vinnytsia Regional Council"

Vinnytsia, , Ukraine

Municipal Nonprofit Enterprise: Zaporizhia Regional Clinical Hospital under Zaporizhia Regional Council, Department of Urology

Zaporizhia, , Ukraine

Countries

United States; Bulgaria; Estonia; Georgia; Israel; Latvia; Poland; Russia; Serbia; Ukraine

References

Prasad SM, Huang WC, Shore ND, Hu B, Bjurlin M, Brown G, Genov P, Shishkov D, Khuskivadze A, Ganev T, Marchev D, Orlov I, Kopyltsov E, Zubarev V, Nosov A, Komlev D, Burger B, Raju S, Meads A, Schoenberg M. Treatment of Low-grade Intermediate-risk Nonmuscle-invasive Bladder Cancer With UGN-102 +/- Transurethral Resection of Bladder Tumor Compared to Transurethral Resection of Bladder Tumor Monotherapy: A Randomized, Controlled, Phase 3 Trial (ATLAS). J Urol. 2023 Oct;210(4):619-629. doi: 10.1097/JU.0000000000003645. Epub 2023 Aug 7.

Reference Type: RESULT

PMID: 37548555 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

BL006

Identifier Type: -

Identifier Source: org_study_id