Clinical trial NCT05243550: A Phase 3 Single-Arm Study of UGN-102 for Treatment of Low-Grade Intermediate-Risk Non-Muscle Invasive Bladder Cancer
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Bladder Cancer
Urothelial Carcinoma
Urothelial Carcinoma Bladder
Keywords: Non-muscle invasive bladder cancer
Low grade non-muscle invasive bladder cancer
Intermediate risk non-muscle invasive bladder cancer
NMIBC
UGN-102
Mitomycin
Lead sponsor: UroGen Pharma Ltd.
Sponsor class: INDUSTRY
First posted: 2022-02-17
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Complete Response Rate (CRR)
timeFrame: 3 months
Secondary outcomes:
measure: Duration of Response (DOR) in Patients Who Achieved CR at the 3-month Visit
timeFrame: Up to 60 months
measure: Durable Complete Response (DCR) Rate in Patients Who Achieved CR at the 3-month Visit
timeFrame: Up to 60 months
measure: Disease-free Survival (DFS) in Patients Who Achieved CR at the 3-month Visit
timeFrame: Up to 63 months
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs of Special Interest
timeFrame: Up to 21 months
measure: Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Hematology Values
timeFrame: 6 months
measure: Number of Participants With Post-baseline PCS Chemistry Values
timeFrame: 6 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Urology Specialists
state: Arizona
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: San Diego
country: United States
facility: Genesis Research
state: California
city: Wichita
country: United States
facility: Wichita Urology Group
state: Kansas
city: Baltimore
country: United States
facility: John Hopkins University
state: Maryland
city: Hanover
country: United States
facility: Chesapeake Urology Research Associates
state: Maryland
city: Columbia
country: United States
facility: University of Missouri
state: Missouri
city: Morristown
country: United States
facility: Atlantic Health System
state: New Jersey
city: Cheektowaga
country: United States
facility: Great Lakes Physician dba WNY Urology Associates
state: New York
city: Garden City
country: United States
facility: AccuMed Research Associates
state: New York
city: New York
country: United States
facility: Manhattan Medical Research
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Mount Sinai
state: New York
city: Nashville
country: United States
facility: Urology Associates, P.C.
state: Tennessee
city: Houston
country: United States
facility: Houston Methodist Research Institute
state: Texas
city: Spokane
country: United States
facility: Spokane Urology, P.S.
state: Washington
city: Vienna
country: Austria
facility: Medical University Vienna, Department of Urology
city: Blagoevgrad
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment - Blagoevgrad
city: Gabrovo
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment "Dr. Tota Venkova", Gabrovo, Department of Urology
city: Lom
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment "Sveti Nikolai Chudotvorets", Lom
city: Montana
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment "City Clinic - Sveti Georgi"
city: Pleven
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment "Dr. Georgi Stranski", Pleven, Urology Clinic
city: Pleven
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment "Sveta Marina" - Pleven, Department of Urology
city: Plovdiv
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment "Sveti Georgi", Plovdiv
city: Plovdiv
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment, Plovdiv
city: Plovdiv
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Park Hospital
city: Ruse
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment 'Kanev', Ruse, Department of Urology
city: Shumen
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment - Shumen, Shumen, Department of Urology
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment "Tsaritsa Yoanna - ISUL", Sofia
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment and Emergency Medicine "N.I. Pirogov", Sofia, Urology Clinic
city: Targovishte
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment - Targovishte
city: Varna
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment "Life Hospital" Burgas
city: Varna
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment, Varna part of Military Medical Academy, Clinic of Urology
city: Varna
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment "Sveta Anna", Varna, Urology Clinic
city: Yambol
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment "Sveti Pantaleymon", Yambol, Department of Urology
city: Kohtla-Järve
country: Estonia
facility: East Viru Central Hospital, Surgery Clinic
city: Tallinn
country: Estonia
facility: East Tallinn Central Hospital Ltd., Surgery Clinic, Centre of Urology
city: Tallinn
country: Estonia
facility: West Tallinn Central Hospital Ltd., Department of Urology
city: Tallinn
country: Estonia
facility: North Estonia Medical Centre Foundation Ltd., Surgery Clinic, General and Oncology Urology Centre
city: Tartu
country: Estonia
facility: Tartu University Hospital, Surgery Clinic, Department of Urology and Kidney Transplantation
city: Tbilisi
country: Georgia
facility: LTD Central University Clinic After Academic N. Kipshidze
city: Tbilisi
country: Georgia
facility: JSC Jerarsi, Department of Urology
city: Tbilisi
country: Georgia
facility: LTD Gidmedi, Urology Department
city: Tbilisi
country: Georgia
facility: Pineo Medical Ecosystem Ltd., Department of Urology
city: Tbilisi
country: Georgia
facility: Tbilisi State Medical University and Ingorokva High Technology Medical Center University Clinic LTD, Urology Department
city: Liepāja
country: Latvia
facility: Liepajas Regional Hospital, Urology Department
city: Riga
country: Latvia
facility: P. Stradins Clinical University Hospital, Center for Urology
city: Riga
country: Latvia
facility: LLC Riga East University Hospital, Clinic of Urology and Oncologic Urology
city: Riga
country: Latvia
facility: Daugavpils Regional Hospital, Urology Department
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health Sciences Kauno Klinikos
city: Klaipėda
country: Lithuania
facility: Klaipeda University Hospital
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santaros Klinikos
city: Gliwice
country: Poland
facility: AKMED
city: Kraków
country: Poland
facility: SCM sp. z o.o. (LLC)
city: Poznań
country: Poland
facility: Clinical Research Center Limited liability company Medic-R Limited partnership
city: Wieliszew
country: Poland
facility: Mazovian Oncology Hospital, Subdepartment of Urology
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia, Clinic of Urology
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Bezanijska Kosa, Clinic of Surgery, Department of Urology
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Zemun, Urology unit
city: Kragujevac
country: Serbia
facility: Clinical Center Kragujevac, Clinic of Urology, Nephrology and Dialysis
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Bilbao
country: Spain
facility: Hospital de Basurto
city: Madrid
country: Spain
facility: University Hospital Foundation Jimenez Diaz
city: Madrid
country: Spain
facility: University Hospital 12 de Octubre
city: Madrid
country: Spain
facility: La Paz University Hospital
Study officials:
affiliation: Atlantic Health System
name: Sandip Prasad, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.