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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03558503
Other study ID # TC-BC-12
Secondary ID
Status Completed
Phase Phase 2
First received
Last updated
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
Health authority
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.

Study Design


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
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