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

Bladder Cancer Clinical Trial

— ATLAS  

Official title:

A Randomized, Controlled, Open-Label Study of the Efficacy, Durability, and Safety of UGN-102 With or Without TURBT in Patients With Low Grade Intermediate Risk Non-Muscle Invasive Bladder Cancer (LG IR NMIBC)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04688931
• Other study ID #: BL006
• Status: Terminated
• Phase: Phase 3
• Start date: February 19, 2021
• Est. completion date: March 17, 2023

Study information

• Verified date: August 2023
• Source: UroGen Pharma Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a global, randomized, controlled, open-label Phase 3 study 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).

Description:

Eligible patients will be randomized in a 1:1 ratio to UGN-102 ± TURBT or TURBT alone. Randomization will be stratified by the presence of a previous LG NMIBC episode within 1 year of the current diagnosis (yes or no). Starting at 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 will undergo TURBT. Patients in both treatment arms will return to the clinic at approximately 3 months after the start of treatment to determine response to treatment. Patients confirmed to have a complete response (CR) will receive no further treatment and will enter the Follow-up Period of the study. Patients confirmed to have a non-complete response (NCR) will undergo TURBT of any remaining lesions and then enter the Follow-up Period of the study. During the Follow-up Period, patients will return to the clinic every 3 months to determine durability of response. Patients will remain on study until completion of all follow-up visits or until disease recurrence, disease progression, or death is documented, whichever occurs first. Patients determined to have a protocol-defined recurrence or progression at any follow-up or unscheduled visit will be 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 information / eligibility

• Status: Terminated
• Enrollment: 282
• Est. completion date: March 17, 2023
• Est. primary completion date: March 17, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 high grade (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 grading 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.

Related Conditions & MeSH terms

• Bladder Cancer
• Carcinoma
• Carcinoma, Transitional Cell
• Urinary Bladder Neoplasms
• Urothelial Carcinoma
• Urothelial Carcinoma Bladder

Intervention

Drug:
• 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, with subsequent conversion to a semi-solid gel depot following instillation into the bladder.

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

Locations

Country	Name	City	State
Bulgaria	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	Ruse
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 "Sveta Anna", Varna, Urology Clinic	Varna
Bulgaria	Multiprofile Hospital for Active Treatment, Varna part of Military Medical Academy, Clinic of Urology	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
Estonia	East Viru Central Hospital, Surgery Clinic	Kohtla-Järve
Estonia	East Tallinn Central Hospital Ltd., Surgery Clinic, Centre of Urology	Tallinn
Estonia	North Estonia Medical Centre Foundation Ltd., Surgery Clinic, General and Oncology Urology Centre	Tallinn
Estonia	West Tallinn Central Hospital Ltd., Department of Urology	Tallinn
Estonia	Tartu University Hospital, Surgery Clinic, Department of Urology and Kidney Transplantation	Tartu
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 Central University Clinic After Academic N. Kipshidze	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
Israel	Edith Wolfson Medical Center	H_olon
Israel	Lady Davis Carmel Medical Center	Haifa
Israel	Rambam Health Care Campus	Haifa
Israel	Rabin Medical Center	Petah tikva
Israel	Chaim Sheba Medical Center	Ramat Gan
Latvia	Liepajas Regional Hospital, Urology Department	Liepaja
Latvia	Daugavpils Regional Hospital, Urology Department	Riga
Latvia	LLC Riga East University Hospital, Clinic of Urology and Oncologic Urology	Riga
Latvia	P. Stradins Clinical University Hospital, Center for Urology	Riga
Poland	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)	Kraków
Poland	"City Clinic" Limited Liability Company	Warsaw
Poland	Miedzyleski Specialist Hospital in Warsaw, Department of Urology	Warsaw
Russian Federation	Sverdlovsk Regional Clinical Hospital #1	Ekaterinburg
Russian Federation	Krasnoyarsk A.I. Kryzhanovsky Regional Oncology Center	Krasnoyarsk
Russian Federation	D.D. Pletnyov City Clinical Hospital, Department of Oncourology	Moscow
Russian Federation	Moscow City Oncology Hospital #62	Moscow
Russian Federation	Murmansk Bayandin Regional Clinical Hospital	Murmansk
Russian Federation	Privolzhsky Regional Medical Center, Urology Department	Nizhny Novgorod
Russian Federation	Tsyb Medical Radiology Research Center, Oncourology Department	Obninsk
Russian Federation	Clinical Oncology Center, Department of Urology and Oncology	Omsk
Russian Federation	N.N. Burdenko Penza Regional Clinical Hospital, Department of Urology	Penza
Russian Federation	Pyatigorsk City Clinical Hospital, Department of Urology	Pyatigorsk
Russian Federation	A.M. Nikiforov Russian Center for Emergency and Radiology Medicine, Department of Urology	Saint Petersburg
Russian Federation	Aleksandrovskaya City Hospital, Department of Urology	Saint Petersburg
Russian Federation	City Hospital #15, Urology Department #12	Saint Petersburg
Russian Federation	First I.P. Pavlov State Medical University of St. Petersburg	Saint Petersburg
Russian Federation	I.I. Mechnikov North-Western State Medical University, Department of Urology	Saint Petersburg
Russian Federation	Leningrad Regional Clinical Oncology Center, Department of Chemotherapy	Saint Petersburg
Russian Federation	Medical and Sanitary Unit #70 of "Passazhiravtotrans"	Saint Petersburg
Russian Federation	N.N. Petrov National Medical Research Center of Oncology, Oncourology Department	Saint Petersburg
Russian Federation	Railway Clinical Hospital under OAO Russian Railways	Saint Petersburg
Russian Federation	St. Luka Clinical Hospital, Department of Urology	Saint Petersburg
Russian Federation	St. Petersburg Clinical Hospital under the Russian Academy of Sciences, Department of Urology	Saint Petersburg
Russian Federation	St.-Petersburg Scientific Research Institute of Phthisiopulmonology	Saint Petersburg
Russian Federation	Siberian State Medical University	Tomsk
Russian Federation	Regional Oncology Center, Tyumen, Oncology Department	Tyumen
Russian Federation	Republican Clinical Oncology Center	Ufa
Russian Federation	Volgograd Regional Center for Urology and Nephrology, Urology Department	Volzhskiy
Russian Federation	Medical Center for Diagnostics and Prevention Plus	Yaroslavl
Serbia	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
Ukraine	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 #4" under Dnipro City Council, Department of Geriatric Urology Care	Dnipro
Ukraine	Public Non-Profit Enterprise "City Clinical Hospital #6" under Dnipro City Council, Department of Urology	Dnipro
Ukraine	Prykarpattia Clinical Oncology Center under Ivano-Frankivsk Regional Council	Ivano-Frankivs'k
Ukraine	Public Non-Profit Enterprise "Regional Clinical Hospital under Ivano-Frankivsk Regional Council", Department of Urology	Ivano-Frankivs'k
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	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-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	Luts'k
Ukraine	Communal Noncommercial Enterprise of Lviv Regional Council "Lviv Regional Clinical Hospital", Department of Urology	Lviv
Ukraine	Municipal Non-Profit Enterprise "Lviv Clinical Emergency Care Hospital", Department of Urology	Lviv
Ukraine	Public Non-profit Enterprise under Lviv Regional Council: Lviv Regional Treatment and Diagnostics Oncology Center	Lviv
Ukraine	Public Non-Profit Enterprise "City Clinical Hospital #10" under Odesa City Council, Department of Urology and Nephrology	Odesa
Ukraine	Public Non-Profit Enterprise "Odesa Regional Clinical Hospital" under Odesa Regional Council	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
United States	Albany Medical Center	Albany	New York
United States	Centers for Advanced Urology, LLP d.b.a Mid-Atlantic Urology	Bala-Cynwyd	Pennsylvania
United States	Chesapeake Urology Research Associates	Baltimore	Maryland
United States	New Jersey Urology	Bloomfield	New Jersey
United States	UNC Chapel Hill Memorial Hospital	Chapel Hill	North Carolina
United States	Great Lakes Physician dba WNY Urology Associates	Cheektowaga	New York
United States	University of Chicago Hospital	Chicago	Illinois
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	New Jersey Urology	Englewood	New Jersey
United States	AccuMed Research Associates	Garden City	New York
United States	Chesapeake Urology Research Associates	Hanover	Maryland
United States	Penn State Health Milton S. Hershey Medical Center and College of Medicine	Hershey	Pennsylvania
United States	First Urology, PSC	Jeffersonville	Indiana
United States	Comprehensive Urologic Care	Lake Barrington	Illinois
United States	Urology Center	Las Vegas	Nevada
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Urology Group of Southern California	Los Angeles	California
United States	Clinical Research Solutions	Middleburg Heights	Ohio
United States	Garden State Urology	Morristown	New Jersey
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	Manhattan Medical Research	New York	New York
United States	Adult & Pediatric Urology, PC	Omaha	Nebraska
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Urology San Antonio	San Antonio	Texas
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	Regional Urology, LLC	Shreveport	Louisiana
United States	Stony Brook Cancer Center	Stony Brook	New York
United States	Associated Medical Professionals of NY, PLLC	Syracuse	New York
United States	Arizona Institute of Urology, PLLC	Tucson	Arizona
United States	Wichita Urology Group	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
UroGen Pharma Ltd.

Countries where clinical trial is conducted

United States,  Bulgaria,  Estonia,  Georgia,  Israel,  Latvia,  Poland,  Russian Federation,  Serbia,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free survival (DFS)	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 HG disease, or death due to any cause.	Up to 21 months
Secondary	Time to recurrence (TTR)	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.	Up to 21 months
Secondary	Complete response rate (CRR)	CRR is defined as the percentage of patients who achieve CR at the 3-month Visit.	3 months
Secondary	Duration of response (DOR)	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.	Up to 18 months
Secondary	Observed CRR at scheduled disease assessment time points	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.	Up to 21 months
Secondary	Incidence of TURBT	Incidence of TURBT is defined as the percentage of patients requiring TURBT and the average number of TURBTs per patient in each treatment arm.	3 months
Secondary	Changes from baseline in health-related quality of life	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).; Descriptive statistics will be used to summarize the scored scales for each of the domains and the change from baseline in the domain scores at each scheduled assessment time point.	Up to 21 months
Secondary	Incidence of treatment-emergent adverse events (TEAEs), serious TEAEs, TEAEs of special interest, and abnormal clinical laboratory test results (hematology, serum chemistry, and urinalysis).	The percentage of patients with each type of event will be summarized.	Up to 21 months