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

Sponsor
UroGen Pharma Ltd. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05243550
Collaborator
(none)
220
Enrollment
82
Locations
1
Arm
71.1
Anticipated Duration (Months)
2.7
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief 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).

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
220 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Mar 1, 2022
Anticipated Primary Completion Date :
Feb 1, 2023
Anticipated Study Completion Date :
Feb 1, 2028

Arms and Interventions

Arm Intervention/Treatment
Experimental: UGN-102

Patients will receive 6 once-weekly intravesical instillations of UGN-102.

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).
Other Names:
  • UGN-102 (mitomycin) for intravesical solution

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Complete response rate (CRR) [3 months]

      CRR is defined as the proportion of patients who achieved CR at the 3-month Visit.

    Secondary Outcome Measures

    1. Duration of response (DOR) [Up to 63 months]

      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.

    2. Durable complete response (DCR) rate [Up to 63 months]

      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.

    3. Disease-free survival (DFS) [Up to 63 months]

      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.

    4. Incidence of treatment-emergent adverse events (TEAEs), serious TEAEs, TEAEs of special interest, and abnormal clinical laboratory test results (hematology, serum chemistry, and urinalysis). [Up to 63 months]

      The number of patients with each type of event will be summarized.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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).

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

    2. 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.

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

    2. 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.

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

    2. Current tumor grading of T1.

    3. Concurrent upper tract urothelial carcinoma (UTUC).

    4. 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.

    5. Is pregnant or breastfeeding.

    6. 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.

    7. 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.

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

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

    10. 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.

    11. 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Arizona Urology Specialists Tucson Arizona United States 85704
    2 Loma Linda University Medical Center Loma Linda California United States 92350
    3 American Institute of Research Los Angeles California United States 90017
    4 Tower Urology Los Angeles California United States 90048
    5 UCLA - University of California, Los Angeles Los Angeles California United States 90095
    6 Genesis Research San Diego California United States 92123
    7 Providence Saint John's Health Center Santa Monica California United States 90404
    8 University of Chicago Hospital Chicago Illinois United States 60637
    9 Indiana University School of Medicine Indianapolis Indiana United States 46202
    10 Wichita Urology Group Wichita Kansas United States 67226
    11 Chesapeake Urology Research Associates Baltimore Maryland United States 21204
    12 John Hopkins University Baltimore Maryland United States 21218
    13 Chesapeake Urology Research Associates Hanover Maryland United States 21076
    14 The Brigham and Women's Hospital, Inc. Boston Massachusetts United States 02115
    15 Michigan Urology Troy Michigan United States 48084
    16 Minnesota Urology Woodbury Minnesota United States 55125
    17 University of Missouri Columbia Missouri United States 65212
    18 Urology Center Las Vegas Las Vegas Nevada United States 89144
    19 New Jersey Urology Bloomfield New Jersey United States 07003
    20 New Jersey Urology Englewood New Jersey United States 07631
    21 Atlantic Health System Morristown New Jersey United States 07960
    22 Rutgers Cancer Institute of New Jersey New Brunswick New Jersey United States 08901
    23 Great Lakes Physician dba WNY Urology Associates Cheektowaga New York United States 14225
    24 AccuMed Research Associates Garden City New York United States 11530
    25 Manhattan Medical Research New York New York United States 10016
    26 NYU Langone Health New York New York United States 10016
    27 Mount Sinai New York New York United States 10029
    28 Premier Medical Group of the Hudson Valley PC Poughkeepsie New York United States 12603
    29 University of Rochester Rochester New York United States 14620
    30 Stony Brook Cancer Center Stony Brook New York United States 11794
    31 Associated Medical Professionals of NY Syracuse New York United States 13210
    32 SUNY Upstate Medical University Syracuse New York United States 13210
    33 TriState Urologic Services PSC INC., dba The Urology Group Cincinnati Ohio United States 45212
    34 Clinical Research Solutions Middleburg Heights Ohio United States 44130
    35 Centers for Advanced Urology, LLP d.b.a Mid-Atlantic Urology Bala-Cynwyd Pennsylvania United States 19004
    36 Penn State Health Milton S. Hershey Medical Center and College of Medicine Hershey Pennsylvania United States 17033
    37 University of Pennsylvania Philadelphia Pennsylvania United States 19104
    38 Urology Associates, P.C. Nashville Tennessee United States 37209
    39 Urology Austin Austin Texas United States 78745
    40 Houston Methodist Research Institute Houston Texas United States 77030
    41 Spokane Urology, P.S. Spokane Washington United States 99202
    42 Multiprofile Hospital for Active Treatment - Blagoevgrad Blagoevgrad Bulgaria 2700
    43 Multiprofile Hospital for Active Treatment "Dr. Tota Venkova", Gabrovo, Department of Urology Gabrovo Bulgaria 5300
    44 Multiprofile Hospital for Active Treatment "Sveti Nikolai Chudotvorets", Lom Lom Bulgaria 3600
    45 Multiprofile Hospital for Active Treatment "City Clinic - Sveti Georgi" Montana Bulgaria 3400
    46 University Multiprofile Hospital for Active Treatment "Dr. Georgi Stranski", Pleven, Urology Clinic Pleven Bulgaria 5800
    47 University Multiprofile Hospital for Active Treatment "Sveta Marina" - Pleven, Department of Urology Pleven Bulgaria 5800
    48 University Multiprofile Hospital for Active Treatment "Sveti Georgi", Plovdiv Plovdiv Bulgaria 4002
    49 University Multiprofile Hospital for Active Treatment, Plovdiv Plovdiv Bulgaria 4003
    50 Multiprofile Hospital for Active Treatment Park Hospital Plovdiv Bulgaria 4109
    51 University Multiprofile Hospital for Active Treatment 'Kanev', Ruse, Department of Urology Ruse Bulgaria 7000
    52 Multiprofile Hospital for Active Treatment - Shumen, Shumen, Department of Urology Shumen Bulgaria 9700
    53 University Multiprofile Hospital for Active Treatment "Tsaritsa Yoanna - ISUL", Sofia Sofia Bulgaria 1527
    54 University Multiprofile Hospital for Active Treatment and Emergency Medicine "N.I. Pirogov", Sofia, Urology Clinic Sofia Bulgaria 1606
    55 University Multiprofile Hospital for Active Treatment "Prof. Dr. Stoyan Kirkovich" Stara Zagora Bulgaria 6000
    56 Multiprofile Hospital for Active Treatment - Targovishte Targovishte Bulgaria 7700
    57 Multiprofile Hospital for Active Treatment "Life Hospital" Burgas Varna Bulgaria 8008
    58 Multiprofile Hospital for Active Treatment, Varna part of Military Medical Academy, Clinic of Urology Varna Bulgaria 9000
    59 Multiprofile Hospital for Active Treatment "Sveta Anna", Varna, Urology Clinic Varna Bulgaria 9002
    60 First Private Hospital Vratsa, Department of Urology Vratsa Bulgaria 3001
    61 Multiprofile Hospital for Active Treatment "Sveti Pantaleymon", Yambol, Department of Urology Yambol Bulgaria 8600
    62 East Viru Central Hospital, Surgery Clinic Kohtla-Järve Estonia 31025
    63 East Tallinn Central Hospital Ltd., Surgery Clinic, Centre of Urology Tallinn Estonia 10138
    64 West Tallinn Central Hospital Ltd., Department of Urology Tallinn Estonia 10617
    65 North Estonia Medical Centre Foundation Ltd., Surgery Clinic, General and Oncology Urology Centre Tallinn Estonia 13419
    66 Tartu University Hospital, Surgery Clinic, Department of Urology and Kidney Transplantation Tartu Estonia 50406
    67 LTD Central University Clinic After Academic N. Kipshidze Tbilisi Georgia 0160
    68 JSC Jerarsi, Department of Urology Tbilisi Georgia
    69 LTD Acad. F. Todua Medical Center - LTD Research Institute of Clinical Medicine, Clinical Research Department Tbilisi Georgia
    70 LTD Gidmedi, Urology Department Tbilisi Georgia
    71 LTD L. Managadze National Center of Urology, Department of Urology Tbilisi Georgia
    72 LTD MMT Hospital, Urology Department Tbilisi Georgia
    73 Pineo Medical Ecosystem Ltd., Department of Urology Tbilisi Georgia
    74 Tbilisi State Medical University and Ingorokva High Technology Medical Center University Clinic LTD, Urology Department Tbilisi Georgia
    75 Liepajas Regional Hospital, Urology Department Liepāja Latvia LV-3414
    76 P. Stradins Clinical University Hospital, Center for Urology Riga Latvia LV-1002
    77 LLC Riga East University Hospital, Clinic of Urology and Oncologic Urology Riga Latvia LV-1038
    78 Daugavpils Regional Hospital, Urology Department Riga Latvia LV-5417
    79 Clinical Center of Serbia, Clinic of Urology Belgrade Serbia 11000
    80 Clinical Hospital Center Bezanijska Kosa, Clinic of Surgery, Department of Urology Belgrade Serbia 11080
    81 Clinical Hospital Center Zemun, Urology unit Belgrade Serbia 11080
    82 Clinical Center Kragujevac, Clinic of Urology, Nephrology and Dialysis Kragujevac Serbia 34000

    Sponsors and Collaborators

    • UroGen Pharma Ltd.

    Investigators

    • Principal Investigator: Sandip Prasad, MD, Atlantic Health System

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    UroGen Pharma Ltd.
    ClinicalTrials.gov Identifier:
    NCT05243550
    Other Study ID Numbers:
    • BL011
    First Posted:
    Feb 17, 2022
    Last Update Posted:
    Aug 25, 2022
    Last Verified:
    Aug 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by UroGen Pharma Ltd.
    Non-muscle invasive bladder cancer
    Low grade non-muscle invasive bladder cancer
    Intermediate risk non-muscle invasive bladder cancer
    NMIBC
    UGN-102
    Mitomycin
    Additional relevant MeSH terms:
    Carcinoma
    Urinary Bladder Neoplasms
    Carcinoma, Transitional Cell
    Mitomycins
    Mitomycin

    Study Results

    No Results Posted as of Aug 25, 2022