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

Nir Kleinmann; Surena F. Matin; Phillip M. Pierorazio; John L. Gore; Ahmad Shabsigh; Brian Hu; Karim Chamie; Guilherme Godoy; Scott Hubosky; Marcelino Rivera; Michael O'Donnell; Marcus Quek; Jay D. Raman; John J. Knoedler; Douglas Scherr; Joshua Stern; Christopher Weight; Alon Weizer; Michael Woods; Hristos Kaimakliotis; Angela B. Smith; Jennifer Linehan; Jonathan Coleman; Mitchell R. Humphreys; Raymond Pak; David Lifshitz; Michael Verni; Mehrad Adibi; Mahul B. Amin; Elyse Seltzer; Ifat Klein; Marina Konorty; Dalit Strauss-Ayali; Gil Hakim; Mark Schoenberg; Seth P. Lerner

doi:10.1016/S1470-2045(20)30147-9

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

Nir Kleinmann, Surena F. Matin, Phillip M. Pierorazio, John L. Gore, Ahmad Shabsigh, Brian Hu, Karim Chamie, Guilherme Godoy, Scott Hubosky, Marcelino Rivera, Michael O'Donnell, Marcus Quek, Jay D. Raman, John J. Knoedler, Douglas Scherr, Joshua Stern, Christopher Weight, Alon Weizer, Michael Woods, Hristos KaimakliotisAngela B. Smith, Jennifer Linehan, Jonathan Coleman, Mitchell R. Humphreys, Raymond Pak, David Lifshitz, Michael Verni, Mehrad Adibi, Mahul B. Amin, Elyse Seltzer, Ifat Klein, Marina Konorty, Dalit Strauss-Ayali, Gil Hakim, Mark Schoenberg, Seth P. Lerner

Urology

Research output: Contribution to journal › Article › peer-review

125 Scopus citations

Abstract

BACKGROUND: Most patients with low-grade upper tract urothelial cancer are treated by radical nephroureterectomy. We aimed to assess the safety and activity of a non-surgical treatment using instillation of UGN-101, a mitomycin-containing reverse thermal gel.

METHODS: In this open-label, single-arm, phase 3 trial, participants were recruited from 24 academic sites in the USA and Israel. Patients (aged ≥18 years) with primary or recurrent biopsy-proven, low-grade upper tract urothelial cancer (measuring 5-15 mm in maximum diameter) and an Eastern Cooperative Oncology Group performance status score of less than 3 (Karnofsky Performance Status score >40) were registered to receive six instillations of once-weekly UGN-101 (mitomycin 4 mg per mL; dosed according to volume of patient's renal pelvis and calyces, maximum 60 mg per instillation) via retrograde catheter to the renal pelvis and calyces. All patients had a planned primary disease evaluation 4-6 weeks after the completion of initial therapy, in which the primary outcome of complete response was assessed, defined as negative 3-month ureteroscopic evaluation, negative cytology, and negative for-cause biopsy. Activity (complete response, expected to occur in >15% of patients) and safety were assessed by the investigator in all patients who received at least one dose of UGN-101. Data presented are from the data cutoff on May 22, 2019. This study is registered with ClinicalTrials.gov, NCT02793128.

FINDINGS: Between April 6, 2017, and Nov 26, 2018, 71 (96%) of 74 enrolled patients received at least one dose of UGN-101. 42 (59%, 95% CI 47-71; p<0·0001) patients had a complete response at the primary disease evaluation visit. The median follow-up for patients with a complete response was 11·0 months (IQR 5·1-12·4). The most frequently reported all-cause adverse events were ureteric stenosis in 31 (44%) of 71 patients, urinary tract infection in 23 (32%), haematuria in 22 (31%), flank pain in 21 (30%), and nausea in 17 (24%). 19 (27%) of 71 patients had study drug-related or procedure-related serious adverse events. No deaths were regarded as related to treatment.

INTERPRETATION: Primary chemoablation of low-grade upper tract urothelial cancer with intracavitary UGN-101 results in clinically significant disease eradication and might offer a kidney-sparing treatment alternative for these patients.

FUNDING: UroGen Pharma.

Original language	English (US)
Pages (from-to)	776-785
Number of pages	10
Journal	The Lancet Oncology
Volume	21
Issue number	6
DOIs	https://doi.org/10.1016/S1470-2045(20)30147-9
State	Published - Jun 2020

Bibliographical note

Funding Information:
This trial was supported with funding from UroGen Pharma (New York, NY, USA). The study team thanks the patients and their families and caregivers for volunteering to participate in this trial. We also wish to thank Kim Thacker of UroGen Pharma for technical support, and Mary Susan Prescott of Prescott Medical Communications Group (Chicago, IL, USA) for editorial assistance with financial support from UroGen Pharma.

Publisher Copyright:
© 2020 Elsevier Ltd

Keywords

Adult
Aged
Aged, 80 and over
Antibiotics, Antineoplastic/administration & dosage
Carcinoma/drug therapy
Drug Carriers
Drug Compounding
Female
Humans
Hydrogels
Israel
Kidney Neoplasms/drug therapy
Male
Middle Aged
Mitomycin/administration & dosage
Neoplasm Grading
Time Factors
Treatment Outcome
United States
Urothelium/drug effects

PubMed: MeSH publication types

Research Support, Non-U.S. Gov't
Multicenter Study
Clinical Trial, Phase III
Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Publisher link

10.1016/S1470-2045(20)30147-9

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Kleinmann, N., Matin, S. F., Pierorazio, P. M., Gore, J. L., Shabsigh, A., Hu, B., Chamie, K., Godoy, G., Hubosky, S., Rivera, M., O'Donnell, M., Quek, M., Raman, J. D., Knoedler, J. J., Scherr, D., Stern, J., Weight, C., Weizer, A., Woods, M., ... Lerner, S. P. (2020). 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. The Lancet Oncology, 21(6), 776-785. https://doi.org/10.1016/S1470-2045(20)30147-9

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. / Kleinmann, Nir; Matin, Surena F.; Pierorazio, Phillip M. et al.
In: The Lancet Oncology, Vol. 21, No. 6, 06.2020, p. 776-785.

Research output: Contribution to journal › Article › peer-review

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 2020, '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', The Lancet Oncology, vol. 21, no. 6, pp. 776-785. https://doi.org/10.1016/S1470-2045(20)30147-9

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title = "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",

abstract = "BACKGROUND: Most patients with low-grade upper tract urothelial cancer are treated by radical nephroureterectomy. We aimed to assess the safety and activity of a non-surgical treatment using instillation of UGN-101, a mitomycin-containing reverse thermal gel.METHODS: In this open-label, single-arm, phase 3 trial, participants were recruited from 24 academic sites in the USA and Israel. Patients (aged ≥18 years) with primary or recurrent biopsy-proven, low-grade upper tract urothelial cancer (measuring 5-15 mm in maximum diameter) and an Eastern Cooperative Oncology Group performance status score of less than 3 (Karnofsky Performance Status score >40) were registered to receive six instillations of once-weekly UGN-101 (mitomycin 4 mg per mL; dosed according to volume of patient's renal pelvis and calyces, maximum 60 mg per instillation) via retrograde catheter to the renal pelvis and calyces. All patients had a planned primary disease evaluation 4-6 weeks after the completion of initial therapy, in which the primary outcome of complete response was assessed, defined as negative 3-month ureteroscopic evaluation, negative cytology, and negative for-cause biopsy. Activity (complete response, expected to occur in >15% of patients) and safety were assessed by the investigator in all patients who received at least one dose of UGN-101. Data presented are from the data cutoff on May 22, 2019. This study is registered with ClinicalTrials.gov, NCT02793128.FINDINGS: Between April 6, 2017, and Nov 26, 2018, 71 (96%) of 74 enrolled patients received at least one dose of UGN-101. 42 (59%, 95% CI 47-71; p<0·0001) patients had a complete response at the primary disease evaluation visit. The median follow-up for patients with a complete response was 11·0 months (IQR 5·1-12·4). The most frequently reported all-cause adverse events were ureteric stenosis in 31 (44%) of 71 patients, urinary tract infection in 23 (32%), haematuria in 22 (31%), flank pain in 21 (30%), and nausea in 17 (24%). 19 (27%) of 71 patients had study drug-related or procedure-related serious adverse events. No deaths were regarded as related to treatment.INTERPRETATION: Primary chemoablation of low-grade upper tract urothelial cancer with intracavitary UGN-101 results in clinically significant disease eradication and might offer a kidney-sparing treatment alternative for these patients.FUNDING: UroGen Pharma.",

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author = "Nir Kleinmann and Matin, {Surena F.} and Pierorazio, {Phillip M.} and Gore, {John L.} and Ahmad Shabsigh and Brian Hu and Karim Chamie and Guilherme Godoy and Scott Hubosky and Marcelino Rivera and Michael O'Donnell and Marcus Quek and Raman, {Jay D.} and Knoedler, {John J.} and Douglas Scherr and Joshua Stern and Christopher Weight and Alon Weizer and Michael Woods and Hristos Kaimakliotis and Smith, {Angela B.} and Jennifer Linehan and Jonathan Coleman and Humphreys, {Mitchell R.} and Raymond Pak and David Lifshitz and Michael Verni and Mehrad Adibi and Amin, {Mahul B.} and Elyse Seltzer and Ifat Klein and Marina Konorty and Dalit Strauss-Ayali and Gil Hakim and Mark Schoenberg and Lerner, {Seth P.}",

note = "Funding Information: This trial was supported with funding from UroGen Pharma (New York, NY, USA). The study team thanks the patients and their families and caregivers for volunteering to participate in this trial. We also wish to thank Kim Thacker of UroGen Pharma for technical support, and Mary Susan Prescott of Prescott Medical Communications Group (Chicago, IL, USA) for editorial assistance with financial support from UroGen Pharma. Publisher Copyright: {\textcopyright} 2020 Elsevier Ltd",

year = "2020",

month = jun,

doi = "10.1016/S1470-2045(20)30147-9",

language = "English (US)",

volume = "21",

pages = "776--785",

journal = "The Lancet Oncology",

issn = "1470-2045",

publisher = "Elsevier Ltd",

number = "6",

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TY - JOUR

T1 - Primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel (OLYMPUS)

T2 - an open-label, single-arm, phase 3 trial

AU - Kleinmann, Nir

AU - Matin, Surena F.

AU - Pierorazio, Phillip M.

AU - Gore, John L.

AU - Shabsigh, Ahmad

AU - Hu, Brian

AU - Chamie, Karim

AU - Godoy, Guilherme

AU - Hubosky, Scott

AU - Rivera, Marcelino

AU - O'Donnell, Michael

AU - Quek, Marcus

AU - Raman, Jay D.

AU - Knoedler, John J.

AU - Scherr, Douglas

AU - Stern, Joshua

AU - Weight, Christopher

AU - Weizer, Alon

AU - Woods, Michael

AU - Kaimakliotis, Hristos

AU - Smith, Angela B.

AU - Linehan, Jennifer

AU - Coleman, Jonathan

AU - Humphreys, Mitchell R.

AU - Pak, Raymond

AU - Lifshitz, David

AU - Verni, Michael

AU - Adibi, Mehrad

AU - Amin, Mahul B.

AU - Seltzer, Elyse

AU - Klein, Ifat

AU - Konorty, Marina

AU - Strauss-Ayali, Dalit

AU - Hakim, Gil

AU - Schoenberg, Mark

AU - Lerner, Seth P.

N1 - Funding Information: This trial was supported with funding from UroGen Pharma (New York, NY, USA). The study team thanks the patients and their families and caregivers for volunteering to participate in this trial. We also wish to thank Kim Thacker of UroGen Pharma for technical support, and Mary Susan Prescott of Prescott Medical Communications Group (Chicago, IL, USA) for editorial assistance with financial support from UroGen Pharma. Publisher Copyright: © 2020 Elsevier Ltd

PY - 2020/6

Y1 - 2020/6

N2 - BACKGROUND: Most patients with low-grade upper tract urothelial cancer are treated by radical nephroureterectomy. We aimed to assess the safety and activity of a non-surgical treatment using instillation of UGN-101, a mitomycin-containing reverse thermal gel.METHODS: In this open-label, single-arm, phase 3 trial, participants were recruited from 24 academic sites in the USA and Israel. Patients (aged ≥18 years) with primary or recurrent biopsy-proven, low-grade upper tract urothelial cancer (measuring 5-15 mm in maximum diameter) and an Eastern Cooperative Oncology Group performance status score of less than 3 (Karnofsky Performance Status score >40) were registered to receive six instillations of once-weekly UGN-101 (mitomycin 4 mg per mL; dosed according to volume of patient's renal pelvis and calyces, maximum 60 mg per instillation) via retrograde catheter to the renal pelvis and calyces. All patients had a planned primary disease evaluation 4-6 weeks after the completion of initial therapy, in which the primary outcome of complete response was assessed, defined as negative 3-month ureteroscopic evaluation, negative cytology, and negative for-cause biopsy. Activity (complete response, expected to occur in >15% of patients) and safety were assessed by the investigator in all patients who received at least one dose of UGN-101. Data presented are from the data cutoff on May 22, 2019. This study is registered with ClinicalTrials.gov, NCT02793128.FINDINGS: Between April 6, 2017, and Nov 26, 2018, 71 (96%) of 74 enrolled patients received at least one dose of UGN-101. 42 (59%, 95% CI 47-71; p<0·0001) patients had a complete response at the primary disease evaluation visit. The median follow-up for patients with a complete response was 11·0 months (IQR 5·1-12·4). The most frequently reported all-cause adverse events were ureteric stenosis in 31 (44%) of 71 patients, urinary tract infection in 23 (32%), haematuria in 22 (31%), flank pain in 21 (30%), and nausea in 17 (24%). 19 (27%) of 71 patients had study drug-related or procedure-related serious adverse events. No deaths were regarded as related to treatment.INTERPRETATION: Primary chemoablation of low-grade upper tract urothelial cancer with intracavitary UGN-101 results in clinically significant disease eradication and might offer a kidney-sparing treatment alternative for these patients.FUNDING: UroGen Pharma.

AB - BACKGROUND: Most patients with low-grade upper tract urothelial cancer are treated by radical nephroureterectomy. We aimed to assess the safety and activity of a non-surgical treatment using instillation of UGN-101, a mitomycin-containing reverse thermal gel.METHODS: In this open-label, single-arm, phase 3 trial, participants were recruited from 24 academic sites in the USA and Israel. Patients (aged ≥18 years) with primary or recurrent biopsy-proven, low-grade upper tract urothelial cancer (measuring 5-15 mm in maximum diameter) and an Eastern Cooperative Oncology Group performance status score of less than 3 (Karnofsky Performance Status score >40) were registered to receive six instillations of once-weekly UGN-101 (mitomycin 4 mg per mL; dosed according to volume of patient's renal pelvis and calyces, maximum 60 mg per instillation) via retrograde catheter to the renal pelvis and calyces. All patients had a planned primary disease evaluation 4-6 weeks after the completion of initial therapy, in which the primary outcome of complete response was assessed, defined as negative 3-month ureteroscopic evaluation, negative cytology, and negative for-cause biopsy. Activity (complete response, expected to occur in >15% of patients) and safety were assessed by the investigator in all patients who received at least one dose of UGN-101. Data presented are from the data cutoff on May 22, 2019. This study is registered with ClinicalTrials.gov, NCT02793128.FINDINGS: Between April 6, 2017, and Nov 26, 2018, 71 (96%) of 74 enrolled patients received at least one dose of UGN-101. 42 (59%, 95% CI 47-71; p<0·0001) patients had a complete response at the primary disease evaluation visit. The median follow-up for patients with a complete response was 11·0 months (IQR 5·1-12·4). The most frequently reported all-cause adverse events were ureteric stenosis in 31 (44%) of 71 patients, urinary tract infection in 23 (32%), haematuria in 22 (31%), flank pain in 21 (30%), and nausea in 17 (24%). 19 (27%) of 71 patients had study drug-related or procedure-related serious adverse events. No deaths were regarded as related to treatment.INTERPRETATION: Primary chemoablation of low-grade upper tract urothelial cancer with intracavitary UGN-101 results in clinically significant disease eradication and might offer a kidney-sparing treatment alternative for these patients.FUNDING: UroGen Pharma.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antibiotics, Antineoplastic/administration & dosage

KW - Carcinoma/drug therapy

KW - Drug Carriers

KW - Drug Compounding

KW - Female

KW - Humans

KW - Hydrogels

KW - Israel

KW - Kidney Neoplasms/drug therapy

KW - Male

KW - Middle Aged

KW - Mitomycin/administration & dosage

KW - Neoplasm Grading

KW - Time Factors

KW - Treatment Outcome

KW - United States

KW - Urothelium/drug effects

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JO - The Lancet Oncology

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ER -

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

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

UN SDGs

Publisher link

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