Clinical trial NCT03558503: A Phase 2b Study of UGN-102 for Low Grade Intermediate Risk Non-Muscle-Invasive Bladder Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bladder Cancer
Urothelial Carcinoma
Urothelial Carcinoma Bladder
Keywords: Non-muscle invasive bladder cancer
Low grade non-muscle invasive bladder cancer
Intermediate risk non-muscle invasive bladder cancer
NMIBC
UGN-102
Mitomycin
Lead sponsor: UroGen Pharma Ltd.
Sponsor class: INDUSTRY
First posted: 2018-06-15
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Complete Response (CR) Rate for UGN-102 Treatment
timeFrame: 3 months after the first instillation of UGN-102
Secondary outcomes:
measure: Durable Complete Response (DCR) Rate
timeFrame: 6, 9, and 12 months after the first instillation of UGN-102
measure: 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.
timeFrame: Up to 12 months
measure: Number of Participants With Post-baseline Potentially Clinically Significant (PCS) Laboratory Values
timeFrame: Up to 12 months
measure: Number of Participants With Post-baseline PCS Vital Signs Values
timeFrame: Up to 12 months
measure: Number of Participants With Post-baseline Clinically Significant (CS) Physical Examination Findings
timeFrame: Up to 12 months
measure: Number of Participants With Post-baseline CS Urology-oriented Physical Examination Findings
timeFrame: Up to 12 months
Other outcomes:
measure: Mitomycin Plasma Concentrations
timeFrame: 0 (pre-instillation), 0.5, 1, 2, 3, 4, 5, and 6 hours after the first instillation of UGN-102
measure: Mitomycin Area Under the Plasma Concentration-time Curve (AUC)
timeFrame: 0 (pre-instillation) to 6 hours after the first instillation of UGN-102
measure: Mitomycin Maximum Plasma Concentration (Cmax)
timeFrame: 0 (pre-instillation), 0.5, 1, 2, 3, 4, 5, and 6 hours after the first instillation of UGN-102
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Cancer Center
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Urology
state: Arkansas
city: Loma Linda
country: United States
facility: Loma Linda University
state: California
city: Santa Monica
country: United States
facility: Providence Medical Institute
state: California
city: Pompano Beach
country: United States
facility: Clinical Research Center of Florida
state: Florida
city: Baltimore
country: United States
facility: John Hopkins University
state: Maryland
city: Omaha
country: United States
facility: Adult & Pediatric Urology, PC
state: Nebraska
city: Las Vegas
country: United States
facility: Urology Las Vegas
state: Nevada
city: New York
country: United States
facility: Manhattan Medical Research
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: New York
country: United States
facility: Montefiore Medical Center (Albert Einstein)
state: New York
city: New York
country: United States
facility: Western New York Urology Associates
state: New York
city: Chapel Hill
country: United States
facility: The University of North Carolina
state: North Carolina
city: Hershey
country: United States
facility: Penn State Hershey State College
state: Pennsylvania
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Nashville
country: United States
facility: Urology Associates, PC
state: Tennessee
city: Fredericksburg
country: United States
facility: Urology San Antonio
state: Texas
city: Haifa
country: Israel
facility: Carmel Medical Center
city: Petah tikva
country: Israel
facility: Rabin Medical Center
Study officials:
affiliation: UroGen Pharma
name: Elyse Seltzer, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.