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

NCT ID: NCT05243550

Last Updated: 2024-11-04

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 240 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-01
• Study Completion Date: 2028-02-29

Brief Summary

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

Detailed Description

Eligible patients received 6 once-weekly intravesical instillations of UGN-102.

All patients returned to the clinic approximately 3 months after the first instillation for determination of response to treatment. Assessment of response was 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 who had a complete response (CR) at the 3-month Visit, defined as having no detectable disease in the bladder, entered the Follow-up Period of the study. Patients who had a non-complete response (NCR) due to residual LG disease underwent investigator-designated standard of care (SOC) treatment of remaining lesions and then entered the Follow-up Period of the study.

During the Follow-up Period, patients 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 be followed 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 who had a disease recurrence during the Follow-up Period or a disease progression at any time underwent investigator-designated SOC treatment and had a separate End of Study (EOS) Visit performed. The timing of the EOS Visit was approximately 3 months after SOC treatment of disease recurrence or progression.

Study conduct is ongoing and data are summarized through a cutoff date of 04 Apr 2024. As of the data cutoff date, ongoing patients were followed through at least Study Month 15, with the earliest enrolled patients followed through Study Month 21.

Conditions

Bladder Cancer; Urothelial Carcinoma; Urothelial Carcinoma Bladder

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

UGN-102

Patients will receive 6 once-weekly intravesical instillations of UGN-102 (75 mg mitomycin).

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.

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

Other Intervention Names

UGN-102 (mitomycin) for intravesical solution

Eligibility Criteria

Inclusion Criteria

1. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form 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 and alanine aminotransferase ≤ 2.5 × ULN;
• Alkaline phosphatase ≤ 2.5 × ULN;
• Estimated glomerular filtration rate ≥ 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 treatment for urothelial carcinoma (UC) within previous 1 year.

2. History of HG bladder cancer (papillary or carcinoma in situ) 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 UC.

9. Evidence of active urinary tract infection 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.

• 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 Urology Specialists

Tucson, Arizona, United States

Loma Linda University Medical Center

Loma Linda, California, United States

Genesis Research

San Diego, California, United States

Wichita Urology Group

Wichita, Kansas, United States

John Hopkins University

Baltimore, Maryland, United States

Chesapeake Urology Research Associates

Hanover, Maryland, United States

University of Missouri

Columbia, Missouri, United States

Atlantic Health System

Morristown, New Jersey, 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

NYU Langone Health

New York, New York, United States

Mount Sinai

New York, New York, United States

Urology Associates, P.C.

Nashville, Tennessee, United States

Houston Methodist Research Institute

Houston, Texas, United States

Spokane Urology, P.S.

Spokane, Washington, United States

Medical University Vienna, Department of Urology

Vienna, , Austria

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

University Multiprofile Hospital for Active Treatment "Sveti Georgi", Plovdiv

Plovdiv, , Bulgaria

University Multiprofile Hospital for Active Treatment, Plovdiv

Plovdiv, , Bulgaria

Multiprofile Hospital for Active Treatment Park Hospital

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 "Tsaritsa Yoanna - ISUL", Sofia

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 "Life Hospital" Burgas

Varna, , 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

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 Gidmedi, 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, , Georgia

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

Hospital of Lithuanian University of Health Sciences Kauno Klinikos

Kaunas, , Lithuania

Klaipeda University Hospital

Klaipėda, , Lithuania

Vilnius University Hospital Santaros Klinikos

Vilnius, , Lithuania

AKMED

Gliwice, , Poland

SCM sp. z o.o. (LLC)

Krakow, , Poland

Clinical Research Center Limited liability company Medic-R Limited partnership

Poznan, , Poland

Mazovian Oncology Hospital, Subdepartment of Urology

Wieliszew, , Poland

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

Hospital del Mar

Barcelona, , Spain

Hospital de Basurto

Bilbao, , Spain

University Hospital Foundation Jimenez Diaz

Madrid, , Spain

University Hospital 12 de Octubre

Madrid, , Spain

La Paz University Hospital

Madrid, , Spain

Countries

United States; Austria; Bulgaria; Estonia; Georgia; Latvia; Lithuania; Poland; Serbia; Spain

References

Prasad SM, Shishkov D, Mihaylov NV, Khuskivadze A, Genov P, Terzi V, Kates M, Huang WC, Louie MJ, Raju S, Burger B, Meads A, Schoenberg M. Primary Chemoablation of Recurrent Low-Grade Intermediate-Risk Nonmuscle-Invasive Bladder Cancer With UGN-102: A Single-Arm, Open-Label, Phase 3 Trial (ENVISION). J Urol. 2025 Feb;213(2):205-216. doi: 10.1097/JU.0000000000004296. Epub 2024 Oct 24.

Reference Type: RESULT

PMID: 39446087 (View on PubMed)

Stover AM, Mueller D, Carda-Auten J, Hilton A, Tsurutis V, Smith AB. Perceived Impact on Patient Routines/Responsibilities for Surgery and a Nonsurgical Primary Treatment Option in Recurrent Low-Grade Intermediate-Risk Nonmuscle-Invasive Bladder Cancer: Findings From the ENVISION Phase 3 Trial. J Urol. 2025 Jul;214(1):18-31. doi: 10.1097/JU.0000000000004511. Epub 2025 Mar 6.

Reference Type: DERIVED

PMID: 40048558 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

BL011

Identifier Type: -

Identifier Source: org_study_id