A Phase 2b Study of UGN-102 for Low Grade Intermediate Risk Non-Muscle-Invasive Bladder Cancer

NCT ID: NCT03558503

Last Updated: 2022-09-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 63 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-15
• Study Completion Date: 2020-10-21

Brief Summary

This Phase 2b, single-arm, multicenter study evaluated 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).

Detailed Description

Eligible patients were treated with 6 once-weekly intravesical instillations of UGN-102.

The ablative effect of UGN-102 was evaluated at the 3-month Visit, which occurred 5 weeks ± 1 week after the last weekly instillation (3 months after initiation of study drug). Response was determined based on visual evaluation by cystoscopy (appearance, number, and size of the lesions) and, if there were remaining lesions, by histopathology of the remaining lesions. Complete response (CR) was defined as having no detectable disease (NDD) and was assessed visually during cystoscopy and also by urine cytology. In the event that the investigator was not sure, and there was suspect tissue, a small biopsy was taken from the suspect tissue to confirm CR in addition to cystoscopy and urine cytology.

Patients who achieved a CR continued to have monthly telephone contacts to document any adverse events (AEs) and changes in concomitant medications and were assessed at 6, 9, and 12 months after the first instillation of UGN-102 for evidence of disease recurrence. Patients who had a non-complete response (non-CR) discontinued the study and continued with standard of care according to their treating physician.

Safety was determined based on a review of AEs, laboratory assessments, and physical examination findings.

Conditions

Bladder Cancer; Urothelial Carcinoma; Urothelial Carcinoma Bladder

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

UGN-102

Patients were treated with 6 once-weekly intravesical instillations of UGN-102.

Group Type: EXPERIMENTAL

UGN-102

Intervention Type: DRUG

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).

Interventions

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).

Intervention Type: DRUG

Other Intervention Names

UGN-102 (mitomycin) for intravesical solution

Eligibility Criteria

Inclusion Criteria

1. Willing and able to sign an informed consent and comply with the protocol.

2. Has newly diagnosed or historic LG NMIBC (Ta) histologically confirmed by cold cup biopsy at screening or within 6 weeks of screening.

3. Is at intermediate risk of recurrence, 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).

4. Has negative voiding cytology for high grade (HG) disease at or within 6 weeks of enrollment.

5. Willing to use 2 acceptable forms of effective contraception from enrollment through 6 months post treatment if the participant is female or the female partner of a male participant and is of childbearing potential (defined as premenopausal women who have not been sterilized).

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 (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN;
• Alkaline phosphatase ≤ 2.5 × ULN;
• Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min.

7. Has no evidence of active urinary tract infection (UTI) at Screening and Baseline visits.

• In the case of symptomatic UTI, the patient will be treated with a full course of antibiotics, and study drug will be postponed until resolution. In the case of asymptomatic bacteriuria, the use of prophylactic antibiotics and postponement of study drug is left to the discretion of the Principal Investigator (PI).

Exclusion Criteria

1. History of carcinoma in situ (CIS) on preliminary cystoscopy within 5 years of enrollment.

2. Received Bacillus Calmette-Guérin (BCG) treatment for urothelial carcinoma (UC) within previous 2 years.

3. History of HG papillary UC in the past 2 years.

4. Known allergy or sensitivity to mitomycin.

5. Clinically significant urethral stricture that would preclude passage of a urethral catheter.

6. History of pelvic radiotherapy.

7. History of:

• Neurogenic bladder;
• Active urinary retention;
• Any other condition that would prohibit normal voiding.

8. Past or current muscle invasive (ie, T2, T3, T4) or metastatic UC or concurrent upper tract urothelial carcinoma (UTUC).

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

10. History of prior treatment with an intravesical chemotherapeutic agent with the exception of a single dose of chemotherapy immediately after any previous transurethral resection of bladder tumors (TURBT).

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

UroGen Pharma Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Elyse Seltzer, MD

Role: STUDY_DIRECTOR

UroGen Pharma

Locations

Mayo Clinic Cancer Center

Phoenix, Arizona, United States

Arkansas Urology

Little Rock, Arkansas, United States

Loma Linda University

Loma Linda, California, United States

Providence Medical Institute

Santa Monica, California, United States

Clinical Research Center of Florida

Pompano Beach, Florida, United States

John Hopkins University

Baltimore, Maryland, United States

Adult & Pediatric Urology, PC

Omaha, Nebraska, United States

Urology Las Vegas

Las Vegas, Nevada, United States

Manhattan Medical Research

New York, New York, United States

Weill Cornell Medical College

New York, New York, United States

Montefiore Medical Center (Albert Einstein)

New York, New York, United States

Western New York Urology Associates

New York, New York, United States

The University of North Carolina

Chapel Hill, North Carolina, United States

Penn State Hershey State College

Hershey, Pennsylvania, United States

Carolina Urologic Research Center

Myrtle Beach, South Carolina, United States

Urology Associates, PC

Nashville, Tennessee, United States

Urology San Antonio

Fredericksburg, Texas, United States

Carmel Medical Center

Haifa, , Israel

Rabin Medical Center

Petah Tikva, , Israel

Countries

United States; Israel

References

Chevli KK, Shore ND, Trainer A, Smith AB, Saltzstein D, Ehrlich Y, Raman JD, Friedman B, D'Anna R, Morris D, Hu B, Tyson M, Sankin A, Kates M, Linehan J, Scherr D, Kester S, Verni M, Chamie K, Karsh L, Cinman A, Meads A, Lahiri S, Malinowski M, Gabai N, Raju S, Schoenberg M, Seltzer E, Huang WC. Primary Chemoablation of Low-Grade Intermediate-Risk Nonmuscle-Invasive Bladder Cancer Using UGN-102, a Mitomycin-Containing Reverse Thermal Gel (Optima II): A Phase 2b, Open-Label, Single-Arm Trial. J Urol. 2022 Jan;207(1):61-69. doi: 10.1097/JU.0000000000002186. Epub 2021 Aug 26.

Reference Type: RESULT

PMID: 34433303 (View on PubMed)

Prasad SM, Louie MJ, Burger B, Tsurutis V, Ugwuoke N, Strauss-Ayali D. Pharmacokinetics of UGN-102, an investigational mitomycin-containing reverse thermal gel for the treatment of non-muscle invasive bladder cancer. Cancer Chemother Pharmacol. 2025 Oct 11;95(1):100. doi: 10.1007/s00280-025-04821-5.

Reference Type: DERIVED

PMID: 41074972 (View on PubMed)

Stover AM, Basak R, Mueller D, Lipman R, Teal R, Hilton A, Giannone K, Waheed M, Smith AB. Minimal Patient-Reported Side Effects for a Chemoablative Gel (UGN-102) Used as Frontline Treatment in Adults with Nonmuscle-Invasive Bladder Cancer. J Urol. 2022 Sep;208(3):580-588. doi: 10.1097/JU.0000000000002747. Epub 2022 May 31.

Reference Type: DERIVED

PMID: 35640276 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

TC-BC-12

Identifier Type: -

Identifier Source: org_study_id