Feasibility of Home Instillation of UGN-102 for Treatment of Low-Grade (LG) Non-Muscle-Invasive Bladder Cancer (NMIBC)

Study Overview
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Brief Summary
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This study aims to demonstrate that home instillation of UGN-102 is a feasible alternative to instillation in a clinical setting, which might mitigate some of the challenges in the patient experience (logistical, expense, and comfort) when receiving treatment for low-grade non-muscle-invasive bladder cancer at intermediate risk of recurrence (LG IR NMIBC).

Official Title
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A Phase 3b, Open-Label, Single-Arm, Multicenter Study to Assess the Feasibility of Home Instillation of UGN-102 for Treatment of Patients With Low-Grade (LG) Non-Muscle-Invasive Bladder Cancer (NMIBC) at Intermediate Risk (IR) of Recurrence

Conditions
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Bladder Cancer, Urothelial Carcinoma, Urothelial Carcinoma Bladder

Intervention / Treatment
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* Drug: UGN-102


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and the protocol. Patient who has newly diagnosed or historic LG NMIBC (Ta) histologically confirmed by cold cup biopsy at Screening or within 8 weeks before Screening. Has IR 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 at the initial Screening Visit). Negative voiding cytology for high-grade (HG) disease within 6 weeks before Screening. Has adequate organ and bone marrow function as determined by routine laboratory tests as below: Leukocytes ≥ 3,000/μL (≥ 3×10^9/L). Absolute neutrophil count ≥ 1,500/μL (≥ 1.5×10^9/L). Platelets ≥ 100,000/μL (≥ 100×10^9/L). Hemoglobin ≥ 9.0 g/dL. Total bilirubin ≤ 1.5 × upper limit of normal (ULN). Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) ≤ 2.5 × ULN. Alkaline phosphatase (ALP) ≤ 2.5 × ULN. Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min. Has no evidence of active urinary tract infection (UTI) at the Screening and baseline visits. Patient is willing to receive instillations of UGN-102 at home (ie, Treatment Visits 2 to 6) by an appropriately trained home health professional. 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 first instillation through 6 months post treatment. Acceptable methods of birth control that are considered to have a low failure rate (ie, less than 1% per year) when used consistently and correctly include implants, injections, combined (estrogen/progesterone) oral contraceptives, intrauterine devices (only hormonal), condoms with spermicide, sexual abstinence, or vasectomized partner. Has an anticipated life expectancy of at least the duration of the trial. Exclusion Criteria: Received Bacillus Calmette-Guérin (BCG) treatment for urothelial carcinoma (UC) within previous 1 year. History of HG bladder cancer (papillary or carcinoma in situ) in the past 2 years. Known allergy or sensitivity to mitomycin that in the Investigator's opinion cannot be readily managed. Clinically significant urethral stricture that would preclude passage of a urethral catheter. History of: neurogenic bladder. active urinary retention. any other condition that would prohibit normal voiding. Past or current T1 UC, muscle invasive UC (ie, T2, T3, T4), metastatic UC, or concurrent upper tract urothelial carcinoma (UTUC). 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. 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 transurethral resection of bladder tumors (TURBT). Has participated in a study with an investigational agent or device within 30 days of enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: UGN-102<br>Patients will receive 6 once-weekly intravesical instillations of UGN-102. Treatment Visit 1 will occur at the investigative site and instillation will be performed by a qualified physician. Treatment Visits 2 to 6 will occur at the patient's home and instillation will be performed by a properly trained and qualified home health professional. | Drug: UGN-102<br>* 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).<br>* Other names: UGN-102 (mitomycin) for intravesical solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events (TEAEs), serious TEAEs, TEAEs of special interest, discontinuations from at home study treatment, and abnormal clinical laboratory tests (hematology, serum chemistry, and urinalysis). | The number of patients with each type of event will be summarized. | up to 3 months | 
| Feasibility questionnaires | Home instillation feasibility questionnaires will be completed by the patient, the home health professional, and the Investigator. Patients will rate their home instillation experience such as comfort, safety/concerns, communication, preference compared to office instillation, and overall experience at each home instillation visit. Patient recommendations regarding home instillation will be collected at the 3-month Visit. Home health professionals will rate their home instillation experience such as comfort, difficulty, concerns, and support with performing the instillation at each home instillation visit. Investigators will provide their feedback on home instillation compared to office instillation, taking into account the experiences of the patient and home health professional, at the 3-month Visit. Data will be summarized descriptively and feasibility of home instillation will be assessed based on the totality of the data. | up to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate (CRR) | CRR is defined as the percentage of patients who achieved CR at the 3-month disease assessment. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-muscle invasive bladder cancer, Low grade non-muscle invasive bladder cancer, Intermediate risk non-muscle invasive bladder cancer, NMIBC, UGN-102, Mitomycin