Clinical trial NCT03374488: Pembrolizumab + Epacadostat vs Pembrolizumab + Placebo in Recurrent or Progressive Metastatic Urothelial Carcinoma
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: UC (Urothelial Cancer)
Keywords: Urothelial carcinoma
programmed cell death protein 1 (PD-1) inhibitor
indoleamine 2,3-dioxygenase (IDO) inhibitor
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2017-12-15
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Objective Response Rate (ORR) With Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo
timeFrame: up to 9 weeks +14 days
Secondary outcomes:
measure: Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Experiencing Adverse Events (AEs)
timeFrame: Up to 8 months
measure: Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab + Placebo as Measured by Number of Participants Discontinuing Study Treatment Due to AE
timeFrame: Up to 8 months
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Ironwood Cancer & Research Centers
state: Arizona
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology Oncology Santa Monica
state: California
city: New Haven
country: United States
facility: Smilow Cancer Center at Yale-New Haven
state: Connecticut
city: Atlanta
country: United States
facility: Northside Hospital, Inc. - GCS/Annex
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Quincy
country: United States
facility: Quincy Medical Group
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: New York
country: United States
facility: NYU Clinical Cancer Center
state: New York
city: Tulsa
country: United States
facility: Oklahoma Cancer Specialists & Research Institute
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina-Hollings Cancer Center
state: South Carolina
city: Knoxville
country: United States
facility: University of Tennessee Medical Center Knoxville
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Fort Worth
country: United States
facility: US Oncology and Research
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Richmond
country: United States
facility: VCU Massey Cancer Center
state: Virginia
city: Wollongong
country: Australia
facility: Southern Medical Day Care Centre
state: New South Wales
city: Heidelberg
country: Australia
facility: Austin Health-Austin Hospital
state: Victoria
city: Kurralta Park
country: Australia
facility: Adelaide Cancer Centre
city: Macquarie Park
country: Australia
facility: Macquarie University Hospital
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Research Institute
state: Ontario
city: Montréal
country: Canada
facility: CIUSSS - Hopital Maisonneuve- Rosemont
state: Quebec
city: Montréal
country: Canada
facility: CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont
state: Quebec
city: Québec
country: Canada
facility: CHU de Quebec-Universite Laval-Hotel Dieu de Quebec
state: Quebec
city: Quebec
country: Canada
facility: CHU de Quebec-Universite Laval-Hotel Dieu de Quebec
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Næstved
country: Denmark
facility: Sjaellands Universitetshospital Naestved
city: Angers
country: France
facility: Institut de Cancerologie de l Ouest Site Paul Papin
city: Avignon
country: France
facility: Clinique Sainte Catherine
city: Caen
country: France
facility: Centre de Lutte Contre le Cancer Francois Baclesse
city: Le Mans
country: France
facility: Clinique Victor Hugo
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Leon Berard
city: Montpellier
country: France
facility: Institut du Cancer de Montpellier
city: Paris
country: France
facility: Hopital Cochin
city: Paris
country: France
facility: Hopital Saint Louis
city: Reims
country: France
facility: Institut Jean Godinot
city: Suresnes
country: France
facility: Centre Medico-Chirurgical Foch
city: Tours
country: France
facility: C.H.U. de Tours - Hopital Bretonneau
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Luebeck
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein. Campus Luebeck
state: Schleswig Holstein
city: Duesseldorf
country: Germany
facility: Universitaetsklinikum Duesseldorf
city: Hamburg
country: Germany
facility: Universitatsklinikum Hamburg-Eppendorf
city: Jena
country: Germany
facility: Universitaetsklinikum Jena
city: Magdeburg
country: Germany
facility: Universitaetsklinikum Magdeburg A.o.R.
city: Muenchen
country: Germany
facility: Klinikum rechts der Isar der Technischen Universitat
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
city: Budapest
country: Hungary
facility: Orszagos Onkologiai Intezet
city: Budapest
country: Hungary
facility: Uzsoki Utcai Korhaz
city: Kaposvár
country: Hungary
facility: Somogy Megyei Kaposi Mor Oktato Korhaz
city: Miskolc
country: Hungary
facility: Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz
city: Pécs
country: Hungary
facility: Pecsi Tudomanyegyetem AOK
city: Szolnok
country: Hungary
facility: Jasz - Nagykun Szolnok megyei Hetenyi Geza Korhaz - Rendelointezet
city: Cork
country: Ireland
facility: Cork University Hospital
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Dublin
country: Ireland
facility: Adelaide & Meath Hospital (Incl NCH)
city: Galway
country: Ireland
facility: University College Hospital Galway
city: Limerick
country: Ireland
facility: University Hospital Limerick
city: Waterford
country: Ireland
facility: Waterford Regional Hospital
city: Be'er Sheva
country: Israel
facility: Soroka Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Petach-Tikwa
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
city: Zerifin
country: Israel
facility: Assaf Harofeh Medical Center
city: Arezzo
country: Italy
facility: Medical Oncology Ospedale San Donato
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione Pascale
city: Padova
country: Italy
facility: Istituto Oncologico Veneto
city: Nagoya
country: Japan
facility: Nagoya University Hospital
state: Aichi
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Tsukuba
country: Japan
facility: University of Tsukuba Hospital
state: Ibaraki
city: Kashihara
country: Japan
facility: Nara Medical University Hospital
state: Nara
city: Ube
country: Japan
facility: Yamaguchi University Hospital
state: Yamaguchi
city: Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Tokyo
country: Japan
facility: Medical Hospital, Tokyo Medical And Dental University
city: Tokyo
country: Japan
facility: Yusen Logistics Co Ltd,. Haneda Logistics Center (MSD DC)
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek Ziekenhuis
city: Amsterdam
country: Netherlands
facility: VU University Medical Center
city: Breda
country: Netherlands
facility: Amphia Ziekenhuis
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Saint Petersburg
country: Russian Federation
facility: Leningrad Regional Oncology Dispensary
state: Leningrad Region, Vsevolozhsky District
city: Ivanovo
country: Russian Federation
facility: Ivanovo Regional Oncology Dispensary
city: Moscow
country: Russian Federation
facility: N.N. Blokhin NMRCO
city: Moscow
country: Russian Federation
facility: Russian Scientific Center of Roentgenoradiology
city: Moscow
country: Russian Federation
facility: National Medical Research Radiological Centre
city: Ryazan'
country: Russian Federation
facility: Ryazan Regional Clinical Oncology Dispensary
city: Saint Petersburg
country: Russian Federation
facility: Pokrovskaya City Hospital
city: Ufa
country: Russian Federation
facility: Clinic of Bashkortostan State Medical University
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Vall D Hebron
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: MD Anderson Cancer Center Madrid
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Santiago De Compostela
country: Spain
facility: Hospital Clinico Universitario de Santiago
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncologia
city: Kaohsiung
country: Taiwan
facility: Chang Gung Medical Foundation. Kaohsiung Branch
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Adana
country: Turkey
facility: Adana Sehir Hastanesi
city: Ankara
country: Turkey
facility: Dr. Abdurrahman Yurtaslan Ankara Onkoloji EAH
city: Antalya
country: Turkey
facility: Akdeniz Universitesi Tip Fakultesi
city: Denizli
country: Turkey
facility: Pamukkale Unv. Tip Fak.
city: Edirne
country: Turkey
facility: Trakya Universitesi Tip Fakultesi
city: Istanbul
country: Turkey
facility: Marmara Universitesi Pendik Arastirma ve Uyg. Hastanesi
city: İzmir
country: Turkey
facility: Dokuz Eylul University Faculty of Medicine
city: Samsun
country: Turkey
facility: Samsun Medical Park Hastanesi
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Trust
state: Surrey
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: London
country: United Kingdom
facility: Barts Health NHS Trust - St Bartholomew s Hospital
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: Plymouth
country: United Kingdom
facility: Plymouth Hospitals NHS Trust
city: Sunderland
country: United Kingdom
facility: Sunderland Royal Hospital
Study officials:
affiliation: Incyte Corporation
name: Mark Jones, MD
role: STUDY_DIRECTOR
References: