A Phase 3 Study of UGN-103 for Treatment of Patients With Low-grade Intermediate-risk Non-muscle Invasive Bladder Cancer

Bladder Cancer Clinical Trial

— UTOPIA  

Official title:

A Phase 3, Single-arm, Multicenter Study to Evaluate the Efficacy and Safety of UGN-103, a Novel Formulation of UGN-102, for the Treatment of Patients With Low-grade (LG) Non-muscle Invasive Bladder Cancer (NMIBC) at Intermediate-risk (IR) of Recurrence

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06331299
• Other study ID #: BL013
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: July 2024
• Est. completion date: March 2026

Study information

• Verified date: April 2024
• Source: UroGen Pharma Ltd.
• Contact: Karrie Hilsinger
• Phone: +1 609-256-8316
• Email: karrie.hilsinger[@]urogen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This Phase 3, single-arm, multicenter study will evaluate the efficacy and safety of UGN-103, a novel formulation of UGN-102, instilled in the urinary bladder of patients with low-grade non-muscle invasive bladder cancer (LG-NMIBC).

Description:

Eligible patients will be treated with UGN-103 once weekly for 6 weeks (a total of 6 doses).

Efficacy will be assessed by the complete response rate (CRR) at the 3-month Visit (approximately 3 months after the first instillation). Response will be determined 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 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. During the Follow-up Period, patients will return to the clinic every 3 months for evaluation of response. Patients will remain on study until disease recurrence, disease progression, death, or the last patient completes 12 months of follow-up (ie, 15 months after the first instillation), whichever occurs first.

Patients who have a non-complete response (NCR) at the 3-month Visit will undergo investigator designated standard of care (SOC) and have a separate End of Study (EOS) Visit performed.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 87
• Est. completion date: March 2026
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Provide 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 at least 1 prior episode of NMIBC. 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:

• Leukocytes = 3,000/µL.

• Absolute neutrophil count = 1,500/µL.

• Platelets = 100,000/µL.

• Hemoglobin = 9.0 g/dL.

• Total bilirubin = 1.5 × 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.

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 (BCG) treatment for urothelial carcinoma (UC) within the 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 any component of the study treatment (including excipients) 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 stage of T1.

8. Concurrent upper tract urothelial carcinoma (UTUC).

9. 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.

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 transurethral resection of bladder tumors (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.

17. Where applicable per country regulation, the patient must not be currently committed to an institution by virtue of an order issued by either judicial or administrative authorities.

Related Conditions & MeSH terms

• Bladder Cancer
• Carcinoma
• Carcinoma, Transitional Cell
• Urinary Bladder Neoplasms
• Urothelial Carcinoma
• Urothelial Carcinoma Bladder

Intervention

Drug:
• UGN-103
UGN-103 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-103 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. The UGN-103 admixture for intravesical instillations contains 75 mg mitomycin in 56 mL admixture (1.33 mg mitomycin per 1 mL).

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
UroGen Pharma Ltd.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete response rate (CRR)	CRR is defined as the proportion of patients who achieved CR at the 3-month Visit.	3 months
Secondary	Duration of response (DOR)	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.	Up to 21 months
Secondary	Durable complete response (DCR) rate	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.	Up to 21 months
Secondary	Incidence of treatment-emergent adverse events (TEAEs), serious TEAEs, TEAEs of special interest, and abnormal clinical laboratory test results (hematology and serum chemistry)	The number of patients with each type of event will be summarized.	Up to 21 months
Secondary	Mitomycin plasma concentrations	Mitomycin plasma concentrations will be assessed in a subset of patients treated with UGN-103	0 (pre-instillation), 0.5, 1, 2, 3, 4, 5, and 6 hours after the first instillation of UGN-103.
Secondary	Mitomycin maximum plasma concentration (Cmax)	Mitomycin Cmax will be assessed in a subset of patients treated with UGN-103	0 (pre-instillation), 0.5, 1, 2, 3, 4, 5, and 6 hours after the first instillation of UGN-103.