Clinical trial NCT02793128: The OLYMPUS Study - Optimized DeLivery of Mitomycin for Primary UTUC Study
Official title: A Phase 3 Multicenter Trial Evaluating the Efficacy and Safety of UGN-101 on Ablation of Upper Urinary Tract Urothelial Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoma, Transitional Cell
Transitional Cell Carcinoma of Renal Pelvis
Keywords: TC-3
UTUC
Ureteral
Upper Tract
Carcinoma
Kidney
Renal
Gel
Local
Mitomycin C
Prolonged Release
Slow Release
Kidney Sparing
T1
T0
Low Grade
Transitional Cell Carcinoma of Renal Pelvis
TCC
UGN-101
Lead sponsor: UroGen Pharma Ltd.
Sponsor class: INDUSTRY
First posted: 2016-06-08
Enrollment: 71
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: The study is investigating the ability of UroGen's UGN-101 to treat urothelial carcinoma tumors from the upper urinary tract.

Detailed description: Trial TC-UT-03 is a prospective, open label, single-arm trial, designed to assess the efficacy, safety, and tolerability of treatment with UGN-101 instilled in the upper urinary system of patients with non-invasive low-grade (LG), Upper Tract Urothelial Carcinoma (UTUC).

Upon signing of informed consent, the patients will undergo a screening visit for eligibility evaluation. Eligible patients will be treated with UGN-101 once weekly for a total of 6 times; in a retrograde fashion. Patients who will demonstrate complete response (CR) will be treated with UGN-101 once monthly as a maintenance therapy for a total of 11 instillations or up to the first recurrence whichever comes first.

Five (5) weeks (± 1 w) following the last instillation, the Primary Disease Evaluation (PDE) Visit, during which safety and efficacy will be assessed, will take place. During this visit, the ablative effect of the UGN-101 will be assessed visually, by upper tract washed urine cytology, and if there are remaining tumors, by biopsy or brush biopsy if technically feasible.

Patient demonstrating CR at PDE will undergo monthly maintenance instillations of UGN-101 up to 11 months post PDE. Safety follow-up for these patients will be done until one month post last instillation or at the end of the follow-up period in FU visit 12, which is the earlier.

For patients who did not demonstrate Complete Response, to the extent that it is possible, all remaining tumors lesions will be biopsied. The patients shall undergo any additional surgical or other treatment the Principal Investigator (PI) decides deem necessary to remove remaining tumor.

An independent Data Monitoring Committee (DMC) was assigned to this trial. Accumulating safety, tolerability and efficacy data will be monitored periodically by the DMC according to a pre-specified process and frequency detailed in the DMC charter.

Eligibility criteria: Main Inclusion Criteria:

1. Patient is at least 18 years of age.
2. Naive or recurrent patients with low grade (LG), non-invasive Upper Tract Urothelial Carcinoma (UTUC) in the pyelocalyceal system.
3. Patient has at least one (1) measurable papillary LG tumor, evaluated visually, ≤ 15 mm. The largest lesion should not exceed 15mm.
4. Biopsy taken from one or more tumors located above the ureteropelvic junction (UPJ) showing LG urothelial carcinoma. Diagnosed not more than 2 months prior to the screening.
5. Patient should have at least one remaining papillary LG tumor evaluated visually with a diameter of at least 5 mm.
6. Wash urine cytology sampled from the pyelocalyceal system documenting the absence of High Grade (HG) urothelial cancer, diagnosed not more than 2 months prior to the screening.
7. Patient with bilateral LG UTUC may be enrolled if at least one side meets the inclusion criteria for the trial and if the other kidney does not require further treatments (The other kidney can be treated prior to the beginning of the study).

Main Exclusion Criteria:

1. Patient received Bacille de Calmette et Guérin (BCG) treatment for Urothelial carcinoma (UC) during the 6 months prior to Visit 1.
2. The patient has untreated concurrent urothelial cancer in other locations other than the target area (unless treated during screening)
3. Carcinoma in situ (CIS) in the past in the urinary tract.
4. Patient has a history of invasive urothelial carcinoma in the urinary tract during the past 5 (Five) years.
5. Patient has a history of high grade papillary urothelial carcinoma in the urinary tract during the past 2 (Two) years.
6. Patient is actively being treated or intends to be treated with systemic chemotherapy during the duration of the trial.

Primary outcomes:
measure: The Primary Efficacy Endpoint Was the Number of Patients Attaining Complete Response (CR) at the End of the Treatment Period (PDE Visit).
timeFrame: An average of 11 weeks
Secondary outcomes:
measure: The Key Secondary Efficacy Endpoint Was Long-term Durability of Complete Response (CR): Number of Patients Who Maintained CR at 12 Month Post PDE Visit. This Endpoint Was Defined Only for Those Patients Who Achieved CR at the PDE Visit.
timeFrame: 12 months
measure: Durability of Complete Response (CR) for Each Follow-up Time Point.
timeFrame: 3, 6, 9 and 12 months
measure: Clinical Benefit for Patients With Partial Response (PR) at the Primary Disease Evaluation (PDE) Visit. Clinical Benefit Endpoint Was Analyzed Using the Intent-to-Treat (ITT) Analysis Set, Including Patients Who Achieved Partial Response at PDE Visit.
timeFrame: An average of 11 weeks
measure: Pharmacokinetic: The PK Profiles of the First UGN-101 Instillation in the Blood Were to be Examined for the First 6 Patients.
timeFrame: Blood samples were collected at 0 minutes (pre-dose) and 30 minutes, 1, 2, 3, 4, 5, and 6 hours following the first instillation of UGN-101
measure: Pharmacokinetic: The PK Profiles of the First UGN-101 Instillation in the Blood Were to be Examined for the First 6 Patients.
timeFrame: Blood samples were collected at 0 minutes (pre-dose) and 30 minutes, 1, 2, 3, 4, 5, and 6 hours following the first instillation with UGN-101
measure: Pharmacokinetic: The PK Profiles of the First UGN-101 Instillation in the Blood Were to be Examined for the First 6 Patients.
timeFrame: Blood samples were collected at 0 minutes (pre-dose) and 30 minutes, 1, 2, 3, 4, 5, and 6 hours following the first instillation with UGN-101
Other outcomes:
measure: Safety Adverse Event Outcomes: Safety Was Monitored Throughout the Study by Reviewing Adverse Events (AEs).
timeFrame: Through study completion, an average of 15 months
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Loma Linda
country: United States
facility: Loma Linda Cancer Center
state: California
city: Los Angeles
country: United States
facility: University of California
state: California
city: Santa Monica
country: United States
facility: Providence Medical Institute
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Maywood
country: United States
facility: Loyola University Medical Center, Department of Urology
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Baltimore
country: United States
facility: John Hopkins University
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic health system
state: Minnesota
city: Las Vegas
country: United States
facility: Urology Center Las Vegas
state: Nevada
city: Bronx
country: United States
facility: Montefiore Medical Center (Albert Einstein)
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of north carolina - chapel hill
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Hershey
country: United States
facility: Penn State College of Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospitals
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance (University of Washington)
state: Washington
city: Petah Tikva
country: Israel
facility: Hasharon Hospital (Rabin Medical Center)
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
Study officials:
affiliation: Baylor College of Medicine
name: Seth Lerner, M.D.
role: STUDY_CHAIR
References:
citation: Shabsigh A, Kleinmann N, Smith AB, Scherr D, Seltzer E, Schoenberg M, Lerner SP. Pharmacokinetics of UGN-101, a mitomycin-containing reverse thermal gel instilled via retrograde catheter for the treatment of low-grade upper tract urothelial carcinoma. Cancer Chemother Pharmacol. 2021 Jun;87(6):799-805. doi: 10.1007/s00280-021-04246-w. Epub 2021 Mar 7.
citation: Kokorovic A, Matin SF. UGN-101 (mitomycin gel): a novel treatment for low-grade upper tract urothelial carcinoma. Ther Adv Med Oncol. 2020 Jul 3;12:1758835920937950. doi: 10.1177/1758835920937950. eCollection 2020.
citation: Kleinmann N, Matin SF, Pierorazio PM, Gore JL, Shabsigh A, Hu B, Chamie K, Godoy G, Hubosky S, Rivera M, O'Donnell M, Quek M, Raman JD, Knoedler JJ, Scherr D, Stern J, Weight C, Weizer A, Woods M, Kaimakliotis H, Smith AB, Linehan J, Coleman J, Humphreys MR, Pak R, Lifshitz D, Verni M, Adibi M, Amin MB, Seltzer E, Klein I, Konorty M, Strauss-Ayali D, Hakim G, Schoenberg M, Lerner SP. Primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel (OLYMPUS): an open-label, single-arm, phase 3 trial. Lancet Oncol. 2020 Jun;21(6):776-785. doi: 10.1016/S1470-2045(20)30147-9. Epub 2020 Apr 29.