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Pembrolizumab + Epacadostat vs Pembrolizumab + Placebo in Recurrent or Progressive Metastatic Urothelial Carcinoma

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ClinicalTrials.gov Identifier: NCT03374488
Recruitment Status : Active, not recruiting
First Posted : December 15, 2017
Results First Posted : August 26, 2019
Last Update Posted : August 26, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Incyte Corporation

Brief Summary:
The purpose of this study was to evaluate the efficacy and safety of pembrolizumab + epacadostat vs pembrolizumab + placebo as a treatment for recurrent or progressive metastatic urothelial carcinoma in patients who have failed a first-line platinum-containing chemotherapy regimen for advanced/metastatic disease.

Condition or disease Intervention/treatment Phase
UC (Urothelial Cancer) Drug: Pembrolizumab Drug: Epacadostat Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 84 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description: The study will be unblinded after the last participant completes Week 9 imaging assessment for efficacy analysis and after appropriate EC/IRB approvals have been received.
Primary Purpose: Treatment
Official Title: A Phase 3 Randomized, Double-Blind Clinical Study of Pembrolizumab + Epacadostat vs Pembrolizumab + Placebo as a Treatment for Recurrent or Progressive Metastatic Urothelial Carcinoma in Patients Who Have Failed a First-Line Platinum-containing Chemotherapy Regimen for Advanced/Metastatic Disease (KEYNOTE-698/ECHO-303)
Actual Study Start Date : December 22, 2017
Actual Primary Completion Date : July 27, 2018
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Pembrolizumab 200 mg + Epacadostat 100 mg BID
Pembrolizumab + epacadostat
Drug: Pembrolizumab
Pembrolizumab administered intravenously Day 1 of each cycle every 3 weeks.
Other Name: MK-3475

Drug: Epacadostat
Epacadostat administered orally twice daily.
Other Name: INCB024360

Active Comparator: Pembrolizumab 200 mg + placebo BID
Pembrolizumab + placebo
Drug: Pembrolizumab
Pembrolizumab administered intravenously Day 1 of each cycle every 3 weeks.
Other Name: MK-3475

Drug: Placebo
Matching placebo administered orally twice daily.




Primary Outcome Measures :
  1. Objective Response Rate (ORR) With Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo [ Time Frame: up to 9 weeks +14 days ]
    ORR was defined as the percentage of participants who had a complete response (CR), disappearance of all target lesions or partial response (PR), >=30% decrease in the sum of the longest diameter of target lesions per RECIST v1.1 by investigator determination.


Secondary Outcome Measures :
  1. Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to 8 months ]
    AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.

  2. Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Discontinuing Study Treatment Due to AE [ Time Frame: Up to 8 months ]
    AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically-confirmed diagnosis of urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra, that is transitional cell, or mixed transitional/non-transitional (predominantly transitional) cell type.
  • Progression or recurrence of urothelial carcinoma following one prior platinum containing chemotherapy regimen for metastatic or unresectable locally advanced disease. A participant who receives a neoadjuvant or adjuvant platinum-containing regimen following cystectomy for localized muscle-invasive urothelial carcinoma is acceptable (without further systemic treatment), if recurrence/progression occurs ≤ 12 months following completion of therapy.
  • Measurable disease based on RECIST v1.1.
  • Have provided an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated for PD-L1 analysis.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Adequate organ function per protocol-defined criteria.

Exclusion Criteria:

  • Urothelial carcinoma that is suitable for local therapy with curative intent.
  • History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful.
  • Known additional malignancy that is progressing or has required active treatment within the past 3 years.
  • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, ie, without evidence of progression for at least 4 weeks by repeat imaging.
  • Active autoimmune disease that has required systemic treatment in past 2 years.
  • Known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by local health authority.
  • Known history of or is positive for active hepatitis B (HBsAg reactive) or has active hepatitis C (HCV RNA). Note: Testing must be performed to determine eligibility.
  • Use of protocol-defined prior/concomitant therapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03374488


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Locations
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United States, Arizona
Ironwood Cancer & Research Centers
Chandler, Arizona, United States, 85224
United States, California
University of California Irvine Medical Center
Orange, California, United States, 92868
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94158
UCLA Hematology Oncology Santa Monica
Santa Monica, California, United States, 90404
United States, Connecticut
Smilow Cancer Center at Yale-New Haven
New Haven, Connecticut, United States, 06510
United States, Georgia
Northside Hospital, Inc. - GCS/Annex
Atlanta, Georgia, United States, 30341
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
Quincy Medical Group
Quincy, Illinois, United States, 62301
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Michigan
University of Michigan Health System
Ann Arbor, Michigan, United States, 48109
United States, New York
NYU Clinical Cancer Center
New York, New York, United States, 10016
United States, Oklahoma
Oklahoma Cancer Specialists & Research Institute
Tulsa, Oklahoma, United States, 74146
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97210
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States, 19107
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
United States, South Carolina
Medical University of South Carolina-Hollings Cancer Center
Charleston, South Carolina, United States, 29425
United States, Tennessee
University of Tennessee Medical Center Knoxville
Knoxville, Tennessee, United States, 37920
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37203
United States, Texas
US Oncology and Research
Fort Worth, Texas, United States, 76177
United States, Virginia
Virginia Cancer Specialists, PC
Fairfax, Virginia, United States, 22031
Virginia Oncology Associates
Norfolk, Virginia, United States, 23502
VCU Massey Cancer Center
Richmond, Virginia, United States, 23298
Australia, New South Wales
Southern Medical Day Care Centre
Wollongong, New South Wales, Australia, 2500
Australia, Victoria
Austin Health-Austin Hospital
Heidelberg, Victoria, Australia, 3084
Australia
Adelaide Cancer Centre
Kurralta Park, Australia, 5037
Macquarie University Hospital
Macquarie Park, Australia, 2109
Canada, Ontario
London Health Sciences Centre
London, Ontario, Canada, N6A 4L6
The Ottawa Hospital Cancer Centre
Ottawa, Ontario, Canada, K1H 8L6
Sunnybrook Research Institute
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
CIUSSS - Hopital Maisonneuve- Rosemont
Montréal, Quebec, Canada, H1T 2M4
CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont
Montréal, Quebec, Canada, H1T 2M4
CHU de Quebec-Universite Laval-Hotel Dieu de Quebec
Québec, Quebec, Canada, G1R 3S1
Canada
CHU de Quebec-Universite Laval-Hotel Dieu de Quebec
Quebec, Canada, G1R 3S1
Denmark
Aalborg University Hospital
Aalborg, Denmark, 9000
Rigshospitalet
Copenhagen, Denmark, 2100
Herlev Hospital
Herlev, Denmark, 2730
Sjaellands Universitetshospital Naestved
Næstved, Denmark, 4700
France
Institut de Cancerologie de l Ouest Site Paul Papin
Angers, France, 49055
Clinique Sainte Catherine
Avignon, France, 84918
Centre de Lutte Contre le Cancer Francois Baclesse
Caen, France, 14000
Clinique Victor Hugo
Le Mans, France, 72000
Centre Oscar Lambret
Lille, France, 59020
Centre Leon Berard
Lyon, France, 69008
Institut du Cancer de Montpellier
Montpellier, France, 34298
Hopital Cochin
Paris, France, 75014
Hopital Saint Louis
Paris, France, 75475
Institut Jean Godinot
Reims, France, 51726
Centre Medico-Chirurgical Foch
Suresnes, France, 92151
C.H.U. de Tours - Hopital Bretonneau
Tours, France, 37044
Institut Gustave Roussy
Villejuif, France, 94805
Germany
Universitaetsklinikum Schleswig-Holstein. Campus Luebeck
Luebeck, Schleswig Holstein, Germany, 23538
Universitaetsklinikum Duesseldorf
Duesseldorf, Germany, 40225
Universitatsklinikum Hamburg-Eppendorf
Hamburg, Germany, 20246
Universitaetsklinikum Jena
Jena, Germany, 07747
Universitaetsklinikum Magdeburg A.o.R.
Magdeburg, Germany, 39120
Klinikum rechts der Isar der Technischen Universitat
Muenchen, Germany, 81675
Universitaetsklinikum Tuebingen
Tuebingen, Germany, 72076
Hungary
Orszagos Onkologiai Intezet
Budapest, Hungary, 1122
Uzsoki Utcai Korhaz
Budapest, Hungary, 1145
Somogy Megyei Kaposi Mor Oktato Korhaz
Kaposvár, Hungary, 7400
Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz
Miskolc, Hungary, 3526
Pecsi Tudomanyegyetem AOK
Pécs, Hungary, 7624
Jasz - Nagykun Szolnok megyei Hetenyi Geza Korhaz - Rendelointezet
Szolnok, Hungary, 5004
Ireland
Cork University Hospital
Cork, Ireland
Beaumont Hospital
Dublin, Ireland, 00009
Adelaide & Meath Hospital (Incl NCH)
Dublin, Ireland, 00024
University College Hospital Galway
Galway, Ireland, H91YR71
University Hospital Limerick
Limerick, Ireland, V94F858
Waterford Regional Hospital
Waterford, Ireland, X91ER8E
Israel
Soroka Medical Center
Be'er Sheva, Israel, 8410101
Rambam Medical Center
Haifa, Israel, 31096
Meir Medical Center
Kfar Saba, Israel, 4428164
Rabin Medical Center
Petach-Tikwa, Israel, 49100
Chaim Sheba Medical Center
Ramat Gan, Israel, 52621
Sourasky Medical Center
Tel Aviv, Israel, 6423906
Assaf Harofeh Medical Center
Zerifin, Israel, 70300
Italy
Medical Oncology Ospedale San Donato
Arezzo, Italy, 52100
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
Meldola, Italy, 47014
Fondazione IRCCS Istituto Nazionale dei Tumori
Milano, Italy, 20133
Istituto Nazionale Tumori Fondazione Pascale
Napoli, Italy, 80131
Istituto Oncologico Veneto
Padova, Italy, 35128
Japan
Nagoya University Hospital
Nagoya, Aichi, Japan, 466-8560
National Cancer Center Hospital East
Kashiwa, Chiba, Japan, 277-8577
University of Tsukuba Hospital
Tsukuba, Ibaraki, Japan, 305-8576
Nara Medical University Hospital
Kashihara, Nara, Japan, 634-8522
Yamaguchi University Hospital
Ube, Yamaguchi, Japan, 755-8505
Osaka International Cancer Institute
Osaka, Japan, 541-8567
Medical Hospital, Tokyo Medical And Dental University
Tokyo, Japan, 113-8519
Yusen Logistics Co Ltd,. Haneda Logistics Center (MSD DC)
Tokyo, Japan, 144-0042
Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of, 03080
Severance Hospital Yonsei University Health System
Seoul, Korea, Republic of, 03722
Asan Medical Center
Seoul, Korea, Republic of, 05505
Samsung Medical Center
Seoul, Korea, Republic of, 06351
Netherlands
Antoni van Leeuwenhoek Ziekenhuis
Amsterdam, Netherlands, 1066 CX
VU University Medical Center
Amsterdam, Netherlands, 1081 HV
Amphia Ziekenhuis
Breda, Netherlands, 4819 EV
Catharina Ziekenhuis
Eindhoven, Netherlands, 5623 EJ
University Medical Center Groningen
Groningen, Netherlands, 9713 GZ
Russian Federation
Leningrad Regional Oncology Dispensary
Saint Petersburg, Leningrad Region, Vsevolozhsky District, Russian Federation, 188663
Ivanovo Regional Oncology Dispensary
Ivanovo, Russian Federation, 153013
N.N. Blokhin NMRCO
Moscow, Russian Federation, 115478
Russian Scientific Center of Roentgenoradiology
Moscow, Russian Federation, 117997
National Medical Research Radiological Centre
Moscow, Russian Federation, 125284
Ryazan Regional Clinical Oncology Dispensary
Ryazan', Russian Federation, 390046
Pokrovskaya City Hospital
Saint Petersburg, Russian Federation, 199106
Clinic of Bashkortostan State Medical University
Ufa, Russian Federation, 450081
Spain
Hospital del Mar
Barcelona, Spain, 08003
Hospital Vall D Hebron
Barcelona, Spain, 08035
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain, 08041
Hospital General Universitario Gregorio Maranon
Madrid, Spain, 28007
MD Anderson Cancer Center Madrid
Madrid, Spain, 28033
Hospital Universitario Virgen de la Victoria
Málaga, Spain, 29010
Hospital Clinico Universitario de Santiago
Santiago De Compostela, Spain, 15706
Instituto Valenciano de Oncologia
Valencia, Spain, 46009
Taiwan
Chang Gung Medical Foundation. Kaohsiung Branch
Kaohsiung, Taiwan, 833
China Medical University Hospital
Taichung, Taiwan, 40447
National Cheng Kung University Hospital
Tainan, Taiwan, 704
National Taiwan University Hospital
Taipei, Taiwan, 100
Taipei Veterans General Hospital
Taipei, Taiwan, 11217
Turkey
Adana Sehir Hastanesi
Adana, Turkey, 01370
Dr. Abdurrahman Yurtaslan Ankara Onkoloji EAH
Ankara, Turkey, 06200
Akdeniz Universitesi Tip Fakultesi
Antalya, Turkey, 07059
Pamukkale Unv. Tip Fak.
Denizli, Turkey, 20070
Trakya Universitesi Tip Fakultesi
Edirne, Turkey, 22030
Marmara Universitesi Pendik Arastirma ve Uyg. Hastanesi
Istanbul, Turkey, 34899
Dokuz Eylul University Faculty of Medicine
İzmir, Turkey, 35340
Samsun Medical Park Hastanesi
Samsun, Turkey, 55200
United Kingdom
Royal Marsden NHS Trust
Sutton, Surrey, United Kingdom, SM2 5PT
Queen Elizabeth Hospital
Birmingham, United Kingdom, B15 2TH
Barts Health NHS Trust - St Bartholomew s Hospital
London, United Kingdom, EC1A 7BE
Royal Free London NHS Foundation Trust
London, United Kingdom, NW3 2QG
Imperial College Healthcare NHS Trust
London, United Kingdom, W6 8RF
Plymouth Hospitals NHS Trust
Plymouth, United Kingdom, PL6 8DH
Sunderland Royal Hospital
Sunderland, United Kingdom, SR4 7TP
Sponsors and Collaborators
Incyte Corporation
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Mark Jones, MD Incyte Corporation
  Study Documents (Full-Text)

Documents provided by Incyte Corporation:

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Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT03374488     History of Changes
Other Study ID Numbers: KEYNOTE-698/ECHO-303
First Posted: December 15, 2017    Key Record Dates
Results First Posted: August 26, 2019
Last Update Posted: August 26, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Incyte Corporation:
Urothelial carcinoma
programmed cell death protein 1 (PD-1) inhibitor
indoleamine 2,3-dioxygenase (IDO) inhibitor
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents