The OLYMPUS Study - Optimized DeLivery of Mitomycin for Primary UTUC Study

NCT02793128 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: TC-UT-03-P
• Study Type: interventional
• Target: 71
• Locations: 2 countries
• Sites: 24

Brief Summary

The study is investigating the ability of UroGen's UGN-101 to treat urothelial carcinoma tumors from the upper urinary tract.

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

Outcome Measures

Primary Outcomes (1)

• The Primary Efficacy Endpoint Was the Number of Patients Attaining Complete Response (CR) at the End of the Treatment Period (PDE Visit).

  The primary efficacy endpoint was the number of patients attaining complete response (CR) at the end of the treatment period (Primary Disease Evaluation (PDE) visit). The CR was defined dichotomously as "Success" if CR was confirmed at PDE visit (or relevant follow-up), and "Failure" otherwise.

  An average of 11 weeks

Secondary Outcomes (6)

• 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.

  12 months

• Durability of Complete Response (CR) for Each Follow-up Time Point.

  3, 6, 9 and 12 months

• 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.

  An average of 11 weeks

• Pharmacokinetic: The PK Profiles of the First UGN-101 Instillation in the Blood Were to be Examined for the First 6 Patients.

  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

• Pharmacokinetic: The PK Profiles of the First UGN-101 Instillation in the Blood Were to be Examined for the First 6 Patients.

  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 (1)

• Safety Adverse Event Outcomes: Safety Was Monitored Throughout the Study by Reviewing Adverse Events (AEs).

  Through study completion, an average of 15 months

Study Arms (1)

UGN-101 instillations

EXPERIMENTAL

The Mitomycin C (MMC) concentration of UGN-101 to be used in this trial will be 4 mg MMC per 1 mL of TC-3 gel, maximum dose is 15ml. 6 once weekly intravesical instillations for the ablation treatment.

Drug: UGN-101 instillations

Interventions

UGN-101 instillations DRUG

Treatment 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.

Also known as: UGN-101

UGN-101 instillations

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is at least 18 years of age.
• Naive or recurrent patients with low grade (LG), non-invasive Upper Tract Urothelial Carcinoma (UTUC) in the pyelocalyceal system.
• Patient has at least one (1) measurable papillary LG tumor, evaluated visually, ≤ 15 mm. The largest lesion should not exceed 15mm.
• 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.
• Patient should have at least one remaining papillary LG tumor evaluated visually with a diameter of at least 5 mm.
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• UroGen Pharma Ltd.: lead

Study Sites (24)

Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

Location

Loma Linda Cancer Center

Loma Linda, California, 92354, United States

Location

University of California

Los Angeles, California, 90095, United States

Location

Providence Medical Institute

Santa Monica, California, 90404, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

Loyola University Medical Center, Department of Urology

Maywood, Illinois, 60153, United States

Location

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

John Hopkins University

Baltimore, Maryland, 21218, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic health system

Rochester, Minnesota, 55905, United States

Location

Urology Center Las Vegas

Las Vegas, Nevada, 89144, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Weill Cornell Medical Center

New York, New York, 10065, United States

Location

Montefiore Medical Center (Albert Einstein)

The Bronx, New York, 10467, United States

Location

University of north carolina - chapel hill

Chapel Hill, North Carolina, 27514, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Penn State College of Medicine

Hershey, Pennsylvania, 17033, United States

Location

Thomas Jefferson University Hospitals

Philadelphia, Pennsylvania, 19107, United States

Location

MD Anderson

Houston, Texas, 77006, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Seattle Cancer Care Alliance (University of Washington)

Seattle, Washington, 98109--1023, United States

Location

Hasharon Hospital (Rabin Medical Center)

Petah Tikva, 49372, Israel

Location

Sheba Medical Center

Ramat Gan, 52621, Israel

Location

Related Publications (4)

• Pierorazio PM, Kleinmann N, Shabsigh A, Hu B, Raman JD, Kaimakliotis H, Sankin A, Singla N, Meads A, Burger B, Raju S, Louie MJ, Chamie K, Weizer A, Schoenberg M. Long-Term Outcomes of Primary Chemoablation of Low-Grade Upper Tract Urothelial Carcinoma With UGN-101, a Mitomycin Reverse Thermal Gel. J Urol. 2025 Mar;213(3):313-322. doi: 10.1097/JU.0000000000004331. Epub 2024 Nov 19.

  PMID: 39561384 DERIVED

• 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.

  PMID: 33677615 DERIVED

• 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.

  PMID: 32670424 DERIVED

• 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.

  PMID: 32631491 DERIVED

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Carcinoma

Interventions

Mitomycin

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Mitomycins; Indolequinones; Quinones; Organic Chemicals; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Madlen Malinowski
• Organization: UroGen Pharma Ltd.

madlen.malinowski@urogen.com

6467689533

Study Officials

• Seth Lerner, M.D.

  Baylor College of Medicine

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2016
• First Posted: June 8, 2016
• Study Start: April 4, 2017
• Primary Completion: April 5, 2019
• Study Completion: March 5, 2020
• Last Updated: December 22, 2020
• Results First Posted: November 20, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

IL (2); US (22)