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

Bladder Cancer Clinical Trial

— ENVISION  

Official title:

A Phase 3, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety of UGN-102 as Primary Chemoablative Therapy in Patients With Low Grade (LG) Non-Muscle-Invasive Bladder Cancer (NMIBC) at Intermediate Risk (IR) of Recurrence

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05243550
• Other study ID #: BL011
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 1, 2022
• Est. completion date: February 2028

Study information

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

Clinical Trial Summary

This Phase 3, multinational, single-arm, multicenter study will evaluate the efficacy and safety of UGN-102 as primary chemoablative therapy in patients with low grade intermediate risk non-muscle-invasive bladder cancer (LG IR NMIBC).

Description:

Eligible patients will receive 6 once-weekly intravesical instillations of UGN-102. All patients will return to the clinic approximately 3 months after the first instillation for determination of response to treatment. Assessment of response will be based on visual observation (white light cystoscopy), histopathology of any remaining or new lesions by central pathology lab (if applicable), and interpretation of urine cytology by central pathology lab. Patients confirmed to have a complete response (CR) at the 3-month Visit, defined as having no detectable disease (NDD) in the bladder, will enter the Follow-up Period of the study. Patients confirmed to have a non-complete response (NCR) will undergo Investigator designated standard of care (SOC) treatment of 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 for up to 24 months (ie, 27 months after the first instillation) for evaluation of response. Patients who remain disease free at the 27-month Visit will continue to return to the clinic every 6 months for up to 36 months (ie, 63 months after the first instillation) or until disease recurrence, disease progression, death, or the study is closed by the Sponsor, whichever occurs first. Patients confirmed to have a disease recurrence during the Follow-up Period or a disease progression at the 3-month Visit or during the Follow-up Period will undergo Investigator designated SOC treatment and have a separate End of Study (EOS) Visit performed. The timing of the EOS Visit will be approximately 3 months after SOC treatment of disease recurrence or progression.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 220
• Est. completion date: February 2028
• Est. primary completion date: April 26, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and the protocol.

2. Patient who has LG NMIBC (Ta) histologically confirmed by cold cup biopsy at Screening or within 8 weeks before Screening.

3. History of LG NMIBC requiring treatment with transurethral resection of bladder tumors (TURBT). Note: This refers to a previous episode(s) and not to the current episode for which the patient is being screened.

4. Has intermediate risk disease, defined as having 1 or 2 of the following:

• Presence of multiple tumors;
• Solitary tumor > 3 cm;
• Early or frequent recurrence (= 1 occurrence of LG NMIBC within 1 year of the current diagnosis at the initial Screening Visit).

5. Negative voiding cytology for high grade (HG) disease within 8 weeks before Screening.

6. Has adequate organ and bone marrow function as determined by routine laboratory tests

as below:

• Leukocytes = 3,000 per µL;
• Absolute neutrophil count = 1,500 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.

7. Has an anticipated life expectancy of at least the duration of the trial.

8. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 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. Received Bacillus Calmette-Guérin (BCG) treatment for urothelial carcinoma (UC) within previous 1 year.

2. History of HG bladder cancer (papillary or carcinoma in situ [CIS]) in the past 2 years.

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

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

5. History of:

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

6. Past or current muscle invasive bladder cancer (ie, T2, T3, T4) or metastatic UC.

7. Current tumor grading of T1.

8. Concurrent upper tract urothelial carcinoma (UTUC).

9. Evidence of active urinary tract infection (UTI) that in the Investigator's opinion cannot be treated and resolved prior to biopsy and/or administration of study treatment.

10. Is pregnant or breastfeeding.

11. 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.

12. History of prior treatment with an intravesical chemotherapeutic agent in the past 2 years except for a single dose of chemotherapy immediately after any previous TURBT.

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

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

15. Has any other active malignancy requiring treatment with systemic anticancer therapy (eg, chemotherapy, immunotherapy, radiation therapy). Superficial cancers such as cutaneous basal cell or squamous cell carcinomas that can be treated locally are allowed.

16. Has any other clinically significant medical or surgical condition that in the Investigator's opinion could compromise patient safety or the interpretation of study results.

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. The UGN-102 admixture for intravesical instillations contains 75 mg mitomycin in 56 mL admixture (1.33 mg mitomycin per 1 mL).

Locations

Country	Name	City	State
Austria	Ordensklinikum Linz GmbH Elisabethinen Hospital, Department of Urology	Linz
Austria	Salzburg Regional Hospital, University Hospital of Urology and Andrology	Salzburg
Austria	Medical University Vienna, Department of Urology	Vienna
Austria	Hospital Wels-Grieskirchen, Department of Urology and Andrology	Wels
Bulgaria	Multiprofile Hospital for Active Treatment - Blagoevgrad	Blagoevgrad
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	Plovdiv
Bulgaria	University Multiprofile Hospital for Active Treatment, Plovdiv	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 "Tsaritsa Yoanna - ISUL", Sofia	Sofia
Bulgaria	University Multiprofile Hospital for Active Treatment and Emergency Medicine "N.I. Pirogov", Sofia, Urology Clinic	Sofia
Bulgaria	University Multiprofile Hospital for Active Treatment "Prof. Dr. Stoyan Kirkovich"	Stara Zagora
Bulgaria	Multiprofile Hospital for Active Treatment - Targovishte	Targovishte
Bulgaria	Multiprofile Hospital for Active Treatment "Life Hospital" Burgas	Varna
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	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	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
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
Lithuania	Hospital of Lithuanian University of Health Sciences Kauno Klinikos	Kaunas
Lithuania	Klaipeda University Hospital	Klaipeda
Lithuania	National Cancer Institute	Vilnius
Lithuania	Vilnius University Hospital Santaros Klinikos	Vilnius
Poland	AKMED	Gliwice
Poland	SCM sp. z o.o. (LLC)	Kraków
Poland	Clinical Research Center Limited liability company Medic-R Limited partnership	Poznan
Poland	Mazovian Oncology Hospital, Subdepartment of Urology	Wieliszew
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
Spain	Hospital del Mar	Barcelona
Spain	Hospital de Basurto	Bilbao
Spain	La Paz University Hospital	Madrid
Spain	University Hospital 12 de Octubre	Madrid
Spain	University Hospital Foundation Jimenez Diaz	Madrid
Spain	Central University Hospital de Asturias (HUCA)	Oviedo
Spain	Navarra University Hospital	Pamplona
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	John Hopkins University	Baltimore	Maryland
United States	New Jersey Urology	Bloomfield	New Jersey
United States	The Brigham and Women's Hospital, Inc.	Boston	Massachusetts
United States	Great Lakes Physician dba WNY Urology Associates	Cheektowaga	New York
United States	TriState Urologic Services PSC INC., dba The Urology Group	Cincinnati	Ohio
United States	University of Missouri	Columbia	Missouri
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	Houston Methodist Research Institute	Houston	Texas
United States	Urology Center Las Vegas	Las Vegas	Nevada
United States	Loma Linda University Medical Center	Loma Linda	California
United States	American Institute of Research	Los Angeles	California
United States	Tower Urology	Los Angeles	California
United States	Clinical Research Solutions	Middleburg Heights	Ohio
United States	Atlantic Health System	Morristown	New Jersey
United States	Urology Associates, P.C.	Nashville	Tennessee
United States	Manhattan Medical Research	New York	New York
United States	Mount Sinai	New York	New York
United States	NYU Langone Health	New York	New York
United States	Premier Medical Group of the Hudson Valley PC	Poughkeepsie	New York
United States	University of Rochester	Rochester	New York
United States	Genesis Research	San Diego	California
United States	Spokane Urology, P.S.	Spokane	Washington
United States	Stony Brook Cancer Center	Stony Brook	New York
United States	Michigan Urology	Troy	Michigan
United States	Arizona Urology Specialists	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,  Austria,  Bulgaria,  Estonia,  Georgia,  Latvia,  Lithuania,  Poland,  Serbia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete response rate (CRR)	CRR is defined as the proportion of patients who achieved CR at the 3-month Visit.	3 months
Secondary	Duration of response (DOR)	DOR is defined as the time from the date of evidence of CR at the 3-month Visit to the earliest date of recurrence or progression or death due to any cause, whichever occurred first.	Up to 63 months
Secondary	Durable complete response (DCR) rate	DCR rate at scheduled disease assessment time points, defined as the proportion of patients who achieved CR at the 3-month Visit and maintained CR (ie, no detectable disease) up to that particular follow-up disease assessment.	Up to 63 months
Secondary	Disease-free survival (DFS)	DFS in patients who achieved CR at the 3-month Visit, defined as the time from first dose to the earliest date of recurrence or progression or death due to any cause, whichever occurred first.	Up to 63 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 number of patients with each type of event will be summarized.	Up to 63 months