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Carcinoma, Transitional CellPhase 3OlympusNCT02793128

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

A Phase 3 study testing UGN-101 instillations in people with Carcinoma, Transitional Cell and Transitional Cell Carcinoma of Renal Pelvis, run by UroGen Pharma Ltd. at 24 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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

Who is it for?
Ages 18 years and older
What is being tested?
UGN-101 instillations
Could I receive a placebo?
No, everyone receives an active treatment
How many people
71 participants
Where
24 sitesin 2 countries
Study dates
4 Apr 2017to 5 Mar 2020
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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.

Trial locations and contacts

24 sites in 2 countries.

24 sites in 2 countries

United States22 sites

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • John Hopkins University

    Baltimore, Maryland, 21218

  • University of north carolina - chapel hill

    Chapel Hill, North Carolina, 27514

  • The Ohio State University Wexner Medical Center

    Columbus, Ohio, 43210

  • Penn State College of Medicine

    Hershey, Pennsylvania, 17033

  • MD Anderson

    Houston, Texas, 77006

  • Baylor College of Medicine

    Houston, Texas, 77030

  • Indiana University School of Medicine

    Indianapolis, Indiana, 46202

  • Mayo Clinic Florida

    Jacksonville, Florida, 32224

  • Urology Center Las Vegas

    Las Vegas, Nevada, 89144

  • Loma Linda Cancer Center

    Loma Linda, California, 92354

  • University of California

    Los Angeles, California, 90095

  • Loyola University Medical Center, Department of Urology

    Maywood, Illinois, 60153

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Weill Cornell Medical Center

    New York, New York, 10065

  • Thomas Jefferson University Hospitals

    Philadelphia, Pennsylvania, 19107

  • Mayo Clinic Hospital

    Phoenix, Arizona, 85054

  • Mayo Clinic health system

    Rochester, Minnesota, 55905

  • Providence Medical Institute

    Santa Monica, California, 90404

  • Seattle Cancer Care Alliance (University of Washington)

    Seattle, Washington, 98109--1023

  • Montefiore Medical Center (Albert Einstein)

    The Bronx, New York, 10467

Other trials in United States

Israel2 sites

  • Hasharon Hospital (Rabin Medical Center)

    Petah Tikva, 49372

  • Sheba Medical Center

    Ramat Gan, 52621

Other trials in Israel

About this study

Official title: A Phase 3 Multicenter Trial Evaluating the Efficacy and Safety of UGN-101 on Ablation of Upper Urinary Tract Urothelial Carcinoma

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

Read the 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.

Being tested
UGN-101 instillations
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
Medical subject headings
Carcinoma, Transitional Cell, Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • UGN-101 instillationsDrug

    Also called UGN-101

    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.

Study groups in NCT02793128
Study groupRoleWhat they receive
UGN-101 instillationsExperimentalThe 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.
Receives: Drug: UGN-101 instillations

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: An average of 11 weeks

Secondary outcomes (6)

  1. 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.

    Continuously: Duration of CR or time-to-recurrence since the Primary Disease Evaluation (PDE) Visit (i.e., time in days from the visit at which CR was determined until recurrence or censoring). This endpoint served as the main long-term durability endpoint. Dichotomously: "Success" if CR was still present at the 12 month post-PDE Visit (at Follow-Up Visit 4), and "Failure" otherwise. This endpoint served as a supportive long-term durability endpoint.

    Measured: 12 months

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

    Durability of CR defined dichotomously as "Success" if CR was achieved at Primary Disease Evaluation (PDE) visit and remained at follow-up Visit 1, Visit 2 and Visit 3 (3, 6, 9 and 12 months post PDE visit), and "Failure" otherwise.

    Measured: 3, 6, 9 and 12 months

  3. 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.

    Clinical benefit for patients with partial response (PR) at the PDE visit. Clinical benefit endpoint was analyzed using the Intent-to-Treat (ITT) Analysis Set, including patients who achieved partial response at PDE Visit.Partial response at PDE visit will be defined dichotomously, similarly to the primary efficacy endpoint. For subjects with partial response at PDE visit, originally planned and actual treatments will be compared.

    Measured: An average of 11 weeks

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

    Cmax: maximum plasma concentration

    Analysis of individual plasma concentration versus time profiles showed that at 6 hours post instillation, the plasma concentrations of all 6 patients were below 2 ng/mL, with the plasma concentration of one patient dropping below the LOQ (i.e., < 0.100 ng/mL). The mean Cmax was 6.24 ng/mL (range: 2.43 to 12.80 ng/mL). The highest individual observed Cmax value of 12.80 ng/mL was 187-fold and 40 fold lower than the observed Cmax level following an intravenous bolus dose of 30 mg or 10 mg mitomycin (2.4 μg/mL and 0.52 μg/mL, respectively) and is 31 fold lower than the threshold value of 400 ng/mL for myelosuppression observed with mitomycin.

    Measured: 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

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

    Tmax: time to maximum plasma concentration

    Analysis of individual plasma concentration versus time profiles showed that at 6 hours post instillation, the plasma concentrations of all 6 patients were below 2 ng/mL, with the plasma concentration of one patient dropping below the LOQ (i.e., < 0.100 ng/mL).

    The mean Cmax was 6.24 ng/mL (range: 2.43 to 12.80 ng/mL), and the Tmax was 1.79 hours (range: 0.50 to 5.17 hours) after instillation. The highest individual observed Cmax value of 12.80 ng/mL was 187-fold and 40 fold lower than the observed Cmax level following an intravenous bolus dose of 30 mg or 10 mg mitomycin (2.4 μg/mL and 0.52 μg/mL, respectively) and is 31 fold lower than the threshold value of 400 ng/mL for myelosuppression observed with mitomycin.

    Measured: 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

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

    Half-life (t½): terminal half-life

    The mean apparent t½ following instillation of mitomycin into the upper urinary tract (UUT) was 1.27 hours (76 minutes), which was longer than the true t½ of mitomycin following a 30 mg bolus injection (mean t½ value of approximately 17 minutes). The apparent t½ demonstrates that UGN-101 dissolved gradually, resulting in prolonged exposure of mitomycin following local instillation into the UUT.

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jun 2016 (estimated)
  2. Study start4 Apr 2017
  3. Primary completion5 Apr 2019
  4. Study completion5 Mar 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
71 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02793128
Sponsor's protocol ID
TC-UT-03-P
Acronym
Olympus
Status last verified
Dec 2020
First submitted
29 May 2016
Last updated
22 Dec 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 39561384

  • 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.

    PubMed 33677615

  • 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.

    PubMed 32670424

  • 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.

    PubMed 32631491

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing UGN-101 instillations in people with Carcinoma, Transitional Cell and Transitional Cell Carcinoma of Renal Pelvis, run by UroGen Pharma Ltd. at 24 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in United States, Israel. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Primary Efficacy Endpoint Was the Number of Patients Attaining Complete Response (CR) at the End of the Treatment Period (PDE Visit). (time frame: An average of 11 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02793128, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2020.

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