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

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

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

The primary objective of this study was to evaluate the feasibility of home instillation of UGN-102 as an alternative to instillation in a clinical setting. Feasibility was assessed by evaluation of safety and tolerability, rate of discontinuation from at home study treatment, and feedback from patients, home health professionals (HHPs), and investigators via standardized questionnaires. The secondary objective of this study was to evaluate the efficacy of UGN-102 for treatment of LG-IR-NMIBC following home instillation. Efficacy was assessed at the 3-month Visit (3 months after the first instillation of UGN-102) by the complete response rate (CRR), defined as the proportion of patients who achieved a complete response (CR) as determined by cystoscopy, for cause biopsy, and urine cytology.

Patients who provided informed consent underwent a Screening Visit to determine eligibility. Screening procedures were to provide evidence of LG-NMIBC and to rule out evidence of high-grade (HG) disease.

Eligible patients were to receive 6 once-weekly intravesical instillations of UGN-102. The first instillation was performed at the investigative site and subsequent instillations were performed at the patient's home by a trained HHP. The HHP was to call the patient 1 to 2 days after each home instillation of UGN-102 to monitor for safety.

At each home instillation visit, the patient and HHP were to complete a feasibility questionnaire. In addition, the patient and investigator were to complete a feasibility questionnaire at the 3-month Visit (end of study) or Early Termination Visit.

Patients were to return to the clinic for the 3-month Visit for determination of response to treatment. Response was determined based on visual evaluation by cystoscopy (white light) (appearance, number, and size of any remaining lesions), interpretation of urine cytology, and for cause biopsy and histopathology of any remaining lesions. Any lesions or suspect tissue were to be biopsied to evaluate for persistence of disease.

Safety was evaluated based on review of adverse events (AEs), laboratory assessments, vital signs, and physical examination.

A patient was considered to have completed the study if the patient completed the 3-month Visit. Following the 3-month Visit, all patients exited the study and continued with standard of care according to their treating physician.

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 newly diagnosed or historic LG-NMIBC (Ta) histologically confirmed by cold cup biopsy at Screening or within 8 weeks before Screening.

3. 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).

4. Negative voiding cytology for HG disease within 6 weeks before Screening.

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

   • 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 × ULN.
   • AST and ALT ≤ 2.5 × ULN.
   • Alkaline phosphatase ≤ 2.5 × ULN.
   • Estimated glomerular filtration rate ≥ 30 mL/min.

6. Has no evidence of active urinary tract infection at the Screening and baseline visits.

7. Patient is willing to receive instillations of UGN-102 at home (ie, Treatment Visits 2 to 6) by an appropriately trained home health professional.

8. 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.

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

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 T1 UC, muscle invasive UC (ie, T2, T3, T4), metastatic UC, or concurrent upper tract UC.

7. 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.

8. 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.

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