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

Bladder Cancer Clinical Trial

— OPTIMA II  

Official title:

A Phase 2b, Single-Arm, Multicenter Trial 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 of Recurrence

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03558503
• Other study ID #: TC-BC-12
• Status: Completed
• Phase: Phase 2
• Start date: October 15, 2018
• Est. completion date: October 21, 2020

Study information

• Verified date: September 2022
• Source: UroGen Pharma Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: October 21, 2020
• Est. primary completion date: January 3, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

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).

Locations

Country	Name	City	State
Israel	Carmel Medical Center	Haifa
Israel	Rabin Medical Center	Petah tikva
United States	John Hopkins University	Baltimore	Maryland
United States	The University of North Carolina	Chapel Hill	North Carolina
United States	Urology San Antonio	Fredericksburg	Texas
United States	Penn State Hershey State College	Hershey	Pennsylvania
United States	Urology Las Vegas	Las Vegas	Nevada
United States	Arkansas Urology	Little Rock	Arkansas
United States	Loma Linda University	Loma Linda	California
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	Urology Associates, PC	Nashville	Tennessee
United States	Manhattan Medical Research	New York	New York
United States	Montefiore Medical Center (Albert Einstein)	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Western New York Urology Associates	New York	New York
United States	Adult & Pediatric Urology, PC	Omaha	Nebraska
United States	Mayo Clinic Cancer Center	Phoenix	Arizona
United States	Clinical Research Center of Florida	Pompano Beach	Florida
United States	Providence Medical Institute	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
UroGen Pharma Ltd.

Countries where clinical trial is conducted

United States,  Israel, 

References & Publications (1)

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, R — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mitomycin Plasma Concentrations	Mitomycin plasma concentrations were assessed in a subset of 6 patients treated with UGN-102	0 (pre-instillation), 0.5, 1, 2, 3, 4, 5, and 6 hours after the first instillation of UGN-102
Other	Mitomycin Area Under the Plasma Concentration-time Curve (AUC)	Mitomycin AUC was assessed in a subset of 6 patients treated with UGN-102	0 (pre-instillation) to 6 hours after the first instillation of UGN-102
Other	Mitomycin Maximum Plasma Concentration (Cmax)	Mitomycin Cmax was assessed in a subset of 6 patients treated with UGN-102	0 (pre-instillation), 0.5, 1, 2, 3, 4, 5, and 6 hours after the first instillation of UGN-102
Primary	Complete Response (CR) Rate for UGN-102 Treatment	To evaluate the tumor ablative effect of UGN-102 in patients with LG NMIBC. CR rate was defined as the percentage of patients with no detectable disease (NDD) as determined by cystoscopy, for cause biopsy, and urine cytology.	3 months after the first instillation of UGN-102
Secondary	Durable Complete Response (DCR) Rate	To evaluate the durability of response in patients with LG NMIBC who achieve CR. DCR rate was defined as the percentage of patients who maintained CR at the respective time point.	6, 9, and 12 months after the first instillation of UGN-102
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Study Drug or Procedure Related TEAEs, TEAEs by Maximum Severity, TEAEs Leading to Treatment Discontinuation, and Serious TEAEs.	The number of patients with each type of event will be summarized. Adverse event severity was graded according to Common Terminology Criteria for Adverse Events version 5.0 as follows: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe or medically significant), Grade 4 (life-threatening), Grade 5 (fatal).	Up to 12 months
Secondary	Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Laboratory Values	The number of patients who met PCS criteria for chemistry or hematology parameters post-baseline will be summarized	Up to 12 months
Secondary	Number of Participants With Post-baseline PCS Vital Signs Values	The number of patients who met PCS criteria for vital signs parameters post-baseline will be summarized	Up to 12 months
Secondary	Number of Participants With Post-baseline Clinically Significant (CS) Physical Examination Findings	The number of patients with abnormal, CS physical examination findings post-baseline will be summarized	Up to 12 months
Secondary	Number of Participants With Post-baseline CS Urology-oriented Physical Examination Findings	The number of patients with abnormal, CS urology-oriented physical examination findings post-baseline will be summarized	Up to 12 months