Clinical trial NCT04191096: Efficacy and Safety of Pembrolizumab (MK-3475) Plus Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus Enzalutamide Plus ADT in Participants With Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) (MK-3475-991/KEYNOTE-991)
Official title: A Phase 3, Randomized, Double-blind Trial of Pembrolizumab (MK-3475) Plus Enzalutamide Plus ADT Versus Placebo Plus Enzalutamide Plus ADT in Participants With Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) (KEYNOTE-991)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Metastatic Hormone-Sensitive Prostate Cancer
Keywords: Programmed Cell Death-1 (PD1, PD-1),
Programmed Death-Ligand 1 (PDL1, PD-L1)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2019-12-09
Enrollment: 1251
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will assess the efficacy and safety of pembrolizumab plus enzalutamide plus Androgen Deprivation Therapy (ADT) versus placebo plus enzalutamide plus ADT in participants with mHSPC. The primary hypothesis is that in participants with mHSPC, the combination of pembrolizumab plus enzalutamide plus ADT is superior to placebo plus enzalutamide plus ADT with respect to 1) radiographic progression-free survival (rPFS) per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by blinded independent central review (BICR) and 2) overall survival (OS). As of 19-JAN-2023, the study was unblinded and all study participants stopped ongoing treatment with pembrolizumab/placebo and will continue to receive Standard of Care treatment until meeting protocol-specified discontinuation criteria if deriving clinical benefit. Safety analysis will be performed at the end of the study; there will be no further analyses for efficacy and electronic patient-reported outcome (ePRO) endpoints collected from participants beyond the IA1 cutoff date. All study participants will stop ongoing treatment with pembrolizumab/placebo. Exceptions may be requested for study participants who, in the assessment of their study physician, are benefitting from the combination of enzalutamide and pembrolizumab, after consulting with the Sponsor. All other study participants should be discontinued from study and be offered standard of care (SOC) treatment as deemed necessary by the Investigator. If enzalutamide as SOC is not accessible off study to the participant, central sourcing may continue. As of Amendment 04, disease progression will no longer be centrally verified, participants will only be assessed locally. As of Amendment 4, Second Course treatment is not an option for participants. There are currently no participants in the Second Course Phase.


Eligibility criteria: Inclusion Criteria:

* Male participants with histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
* Has metastatic disease assessed by investigator and verified by BICR by either ≥2 bone lesions on bone scan and/or visceral disease by computed tomography/magnetic resonance imaging (CT/MRI)
* Willing to maintain continuous Androgen Deprivation Therapy (ADT) with a luteinizing-hormone releasing hormone (LHRH) agonists or antagonists during study treatment or have a history of bilateral orchiectomy
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 10 days of randomization
* Participants receiving bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses prior to randomization
* Has adequate organ function
* Has provided newly obtained core or excisional biopsy (obtained within 12 months of screening) from soft tissue not previously irradiated (samples from tumors progressing in a prior site of radiation are allowed). Participants with bone only or bone predominant disease may provide a bone biopsy sample
* Male participants must agree to the following during the intervention period and for at least 120 days after the last dose of study intervention: Refrain from donating sperm PLUS either be abstinent from heterosexual intercourse and agree to remain abstinent OR agree to use contraception, unless confirmed to be azoospermic
* Male participants must agree to use male condom when engaging in any activity that allows for passage of ejaculate to another person of any sex

Exclusion Criteria:

* Has a known additional malignancy that is progressing or has required active treatment in the last 3 years
* Has an active autoimmune disease that has required systemic treatment in past 2 years
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
* Has undergone major surgery including local prostate intervention (excluding prostate biopsy) within 28 days prior to randomization and not recovered adequately from the toxicities and/or complications
* Has a gastrointestinal disorder affecting absorption or is unable to swallow tablets/capsules
* Has an active infection (including tuberculosis) requiring systemic therapy
* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
* Has known active human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
* Has known or suspected central nervous system (CNS) metastases and/or carcinomatous meningitis
* Has a history of seizure or any condition that may predispose to seizure
* Has a history of loss of consciousness within 12 months of screening
* Has had myocardial infarction or uncontrolled angina within 6 months prior to randomization, or has New York Heart Association class III or IV congestive heart failure or a history of New York Heart Association class III or IV congestive heart failure
* Has hypotension (systolic blood pressure \<86 millimeters of mercury \[mmHg\]) or uncontrolled hypertension (systolic blood pressure \>170 mmHg or diastolic blood pressure \>105 mmHg) at the screening visit
* Has a history of clinically significant ventricular arrhythmias
* Has hypersensitivity to pembrolizumab and/or enzalutamide and/or any of their excipients
* Has received prior ADT as neoadjuvant/adjuvant therapy for non-metastatic prostate cancer for \>39 months in duration or within 9 months prior to randomization or with evidence of disease progression while receiving ADT
* Has had prior treatment with a next generation hormonal agent (eg, abiraterone, enzalutamide, apalutamide, darolutamide)
* Has received prior therapy with an anti-programmed cell death-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-programmed cell death-ligand 2 (anti PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
* Has received a live vaccine within 30 days prior to randomization
* Has a "superscan" bone scan
* Has had an allogenic tissue/solid organ transplant
* Is expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
* Has received any prior pharmacotherapy, radiation therapy or surgery for metastatic prostate cancer with the following exceptions:

  1. Up to 3 months of ADT or orchiectomy with or without concurrent first-generation antiandrogens, if patient was not treated with docetaxel
  2. May have 1 course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease if it was administered at least 4 weeks prior to randomization
  3. For participants with low volume metastatic disease, may have 1 course of definitive radiotherapy if it was administered at least 4 weeks prior to randomization
  4. Up to 6 cycles of docetaxel therapy with final treatment administration completed within 2 months of randomization and no evidence of disease progression. In these participants up to 6 months of ADT permitted

Primary outcomes:
measure: Radiographic Progression-free Survival (rPFS) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
timeFrame: Up to approximately 32 months
measure: Overall Survival (OS)
timeFrame: Up to approximately 32 months
Secondary outcomes:
measure: Time to Initiation of the First Subsequent Anti-cancer Therapy or Death (TFST)
timeFrame: Up to Approximately 32 months
measure: Time to First Symptomatic Skeletal-related Event (TTSSRE)
timeFrame: Up to Approximately 32 months
measure: Time to Prostate-specific Antigen (PSA) Progression
timeFrame: Up to Approximately 32 months
measure: Time to Radiographic Soft Tissue Progression Per Soft Tissue Rules of PCWG-Modified RECIST 1.1 as Assessed by BICR
timeFrame: Up to Approximately 32 months
measure: Time to Pain Progression (TTPP) as Assessed by Brief Pain Inventory-Short Form (BPI-SF) Item #3 ("Worst Pain in 24 Hours") and Opiate Use
timeFrame: Up to Approximately 32 months
measure: Time From Randomization to Disease Progression as Determined by Investigator Assessment After Next-line of Therapy or Death From Any Cause, Whichever Occurs First (PFS2)
timeFrame: Up to Approximately 32 months
measure: Prostate-specific Antigen (PSA) Response Rate
timeFrame: Up to Approximately 32 Months
measure: Prostate-specific Antigen (PSA) Undetectable
timeFrame: Up to Approximately 32 Months
measure: Objective Response Rate (ORR) Per PCWG-Modified RECIST 1.1 as Assessed by BICR
timeFrame: Up to Approximately 32 Months
measure: Duration of Response (DOR) Per PCWG- Modified RECIST 1.1 as Assessed by BICR
timeFrame: Up to Approximately 32 Months
measure: Number of Participants Who Experience an Adverse Event (AE)
timeFrame: Up to Approximately 59 Months
measure: Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
timeFrame: Up to Approximately 59 Months
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Clinical Research Center ( Site 0274)
state: Alaska
city: Anchorage
country: United States
facility: Providence Alaska Medical Center ( Site 0276)
state: Alaska
city: Duarte
country: United States
facility: City of Hope Medical Center ( Site 0217)
state: California
city: Los Angeles
country: United States
facility: UCLA Hematology/Oncology - Santa Monica ( Site 0241)
state: California
city: Aurora
country: United States
facility: University of Colorado, Anschutz Cancer Pavilion ( Site 0236)
state: Colorado
city: Manchester
country: United States
facility: Hartford HealthCare Medical Group ( Site 0212)
state: Connecticut
city: New Haven
country: United States
facility: Smilow Cancer Center at Yale-New Haven ( Site 0250)
state: Connecticut
city: Washington
country: United States
facility: Sibley Memorial Hospital ( Site 0275)
state: District of Columbia
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University ( Site 0209)
state: Georgia
city: Chicago
country: United States
facility: The University of Chicago ( Site 0264)
state: Illinois
city: Springfield
country: United States
facility: Springfield Clinic [Springfield, IL] ( Site 0240)
state: Illinois
city: Topeka
country: United States
facility: Cotton-O'Neil Cancer Center ( Site 0228)
state: Kansas
city: Baltimore
country: United States
facility: The Sidney Kimmel Comprehensive Cancer Center ( Site 0204)
state: Maryland
city: Billings
country: United States
facility: St. Vincent Frontier Cancer Center-Research ( Site 0213)
state: Montana
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada ( Site 0269)
state: Nevada
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0270)
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College ( Site 0263)
state: New York
city: Syracuse
country: United States
facility: Associated Medical Professionals of NY ( Site 0251)
state: New York
city: Durham
country: United States
facility: Duke University ( Site 0206)
state: North Carolina
city: Cincinnati
country: United States
facility: Tri-State Urologic Services PSC, Inc. ( Site 0253)
state: Ohio
city: Bala-Cynwyd
country: United States
facility: MidLantic Urology ( Site 0273)
state: Pennsylvania
city: Charleston
country: United States
facility: Ralph H. Johnson VA Center ( Site 0256)
state: South Carolina
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center ( Site 0259)
state: South Carolina
city: Nashville
country: United States
facility: Urology Associates [Nashville, TN] ( Site 0233)
state: Tennessee
city: Fairfax
country: United States
facility: Inova Health System ( Site 0205)
state: Virginia
city: Virginia Beach
country: United States
facility: Urology of Virginia ( Site 0224)
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance ( Site 0258)
state: Washington
city: Camperdown
country: Australia
facility: Chris OBrien Lifehouse ( Site 0300)
state: New South Wales
city: Port Macquarie
country: Australia
facility: Port Macquarie Base Hospital ( Site 0301)
state: New South Wales
city: Wagga Wagga
country: Australia
facility: Riverina Cancer Care Center ( Site 0302)
state: New South Wales
city: Greenslopes
country: Australia
facility: Gallipoli Medical Research Foundation ( Site 0309)
state: Queensland
city: Tugun
country: Australia
facility: John Flynn Hospital & Medical Centre ( Site 0308)
state: Queensland
city: Box Hill
country: Australia
facility: Box Hill Hospital ( Site 0304)
state: Victoria
city: Clayton
country: Australia
facility: Monash Health ( Site 0305)
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre ( Site 0306)
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital ( Site 0311)
state: Western Australia
city: Linz
country: Austria
facility: Ordensklinikum Linz GmbH Elisabethinen ( Site 0901)
state: Oberosterreich
city: Salzburg
country: Austria
facility: Landeskrankenhaus Salzburg - Universitatklinikum der PMU ( Site 0900)
city: Wien
country: Austria
facility: Krankenhaus der Barmherzigen Brüder Wien ( Site 0904)
city: Wien
country: Austria
facility: Medizinische Universitaet Wien ( Site 0903)
city: Fortaleza
country: Brazil
facility: Oncocentro Ceara ( Site 2309)
state: Ceara
city: Curitiba
country: Brazil
facility: Instituto de Cancer e Transplante de Curitiba ICTR ( Site 2306)
state: Parana
city: Passo Fundo
country: Brazil
facility: Hospital Sao Vicente de Paulo ( Site 2303)
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre ( Site 2304)
state: Rio Grande Do Sul
city: Blumenau
country: Brazil
facility: Clinica de Oncologia Reichow ( Site 2308)
state: Santa Catarina
city: Jau
country: Brazil
facility: Fundacao Dr Amaral Carvalho ( Site 2302)
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 2305)
city: Ottawa
country: Canada
facility: The Ottawa Hospital ( Site 0100)
state: Ontario
city: St. Catharines
country: Canada
facility: Niagara Health System - St. Catharines ( Site 0107)
state: Ontario
city: Greenfield Park
country: Canada
facility: CISSS de la Monteregie-Centre ( Site 0105)
state: Quebec
city: Montreal
country: Canada
facility: Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0109)
state: Quebec
city: Montreal
country: Canada
facility: CIUSSS Ouest de l Ile - St-Mary s Hospital ( Site 0106)
state: Quebec
city: Quebec
country: Canada
facility: CHUQ-Univ Laval-Hotel Dieu de Quebec ( Site 0101)
city: Temuco
country: Chile
facility: Centro Investigación del Cáncer James Lind ( Site 2401)
state: Araucania
city: La Serena
country: Chile
facility: IC La Serena Research ( Site 2406)
state: Coquimbo
city: Talca
country: Chile
facility: Clinica Universidad Catolica del Maule ( Site 2407)
state: Maule
city: Santiago
country: Chile
facility: Clinica Alemana ( Site 2408)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Pontificia Universidad Catolica de Chile ( Site 2402)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Sociedad Medica Aren y Bachero Limitada ( Site 2403)
state: Region M. De Santiago
city: Vina del Mar
country: Chile
facility: Oncocentro ( Site 2400)
state: Valparaiso
city: Beijing
country: China
facility: Peking University First Hospital ( Site 0800)
state: Beijing
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital ( Site 0809)
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University ( Site 0834)
state: Zhejiang
city: Barranquilla
country: Colombia
facility: Institucion Prestadora de Servicios de Salud Clinica de la Costa LTDA ( Site 2504)
state: Atlantico
city: Valledupar
country: Colombia
facility: Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 2509)
state: Cesar
city: Bogota
country: Colombia
facility: Administradora Country SA - Clinica del Country ( Site 2507)
state: Distrito Capital De Bogota
city: Bogota
country: Colombia
facility: Instituto Nacional de Cancerologia E.S.E ( Site 2506)
state: Distrito Capital De Bogota
city: Cali
country: Colombia
facility: Hemato Oncologos ( Site 2503)
state: Valle Del Cauca
city: Copenhagen
country: Denmark
facility: Rigshospitalet ( Site 1005)
state: Hovedstaden
city: Herlev
country: Denmark
facility: Herlev og Gentofte Hospital. ( Site 1004)
state: Hovedstaden
city: Aalborg
country: Denmark
facility: Aalborg Universitetshospital ( Site 1000)
state: Nordjylland
city: Odense
country: Denmark
facility: Odense Universitetshospital ( Site 1003)
state: Syddanmark
city: Vejle
country: Denmark
facility: Vejle Sygehus ( Site 1002)
state: Syddanmark
city: Jyvaskyla
country: Finland
facility: Keski-Suomen keskussairaala ( Site 1017)
state: Mellersta Finland
city: Tampere
country: Finland
facility: Tampereen yliopistollinen sairaala ( Site 1022)
state: Pirkanmaa
city: Helsinki
country: Finland
facility: HYKS ( Site 1020)
state: Varsinais-Suomi
city: Turku
country: Finland
facility: TYKS T-sairaala Syopatautien pkl ( Site 1019)
state: Varsinais-Suomi
city: Lyon
country: France
facility: Centre Leon-Berard ( Site 1110)
state: Auvergne
city: Strasbourg
country: France
facility: Institut de cancérologie Strasbourg Europe (ICANS) ( Site 1114)
state: Bas-Rhin
city: Brest
country: France
facility: CHU de Brest -Site Hopital Morvan ( Site 1103)
state: Bretagne
city: Dijon
country: France
facility: Centre Georges Francois Leclerc ( Site 1112)
state: Cote-d Or
city: Besancon
country: France
facility: CHU-Jean Minjoz ( Site 1101)
state: Doubs
city: Bordeaux
country: France
facility: Institut Bergonie ( Site 1104)
state: Gironde
city: Suresnes
country: France
facility: Hopital Foch ( Site 1105)
state: Hauts-de-Seine
city: Rennes
country: France
facility: C.H.R.U. de Rennes. Hopital de Pontchaillou ( Site 1117)
state: Ille-et-Vilaine
city: Reims
country: France
facility: Institut Jean Godinot-Clinical Research Unit ( Site 1118)
state: Marne
city: Nancy
country: France
facility: Centre D Oncologie de Gentilly ( Site 1107)
state: Meurthe-et-Moselle
city: Lille
country: France
facility: Centre Bourgogne ( Site 1119)
state: Nord-Pas-de-Calais
city: Pierre Benite
country: France
facility: Hospices Civils de Lyon Centre Hospitalier Lyon Sud ( Site 1102)
state: Rhone
city: Creteil
country: France
facility: Hopital Henri Mondor ( Site 1116)
state: Val-de-Marne
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg ( Site 1200)
state: Baden-Wurttemberg
city: Muenchen
country: Germany
facility: Klinikum der Universitaet Muenchen - Grosshadern ( Site 1210)
state: Bayern
city: Munchen
country: Germany
facility: Klinikum Rechts der Isar ( Site 1206)
state: Bayern
city: Nurnberg
country: Germany
facility: Klinikum Nuernberg Nord ( Site 1213)
state: Bayern
city: Braunschweig
country: Germany
facility: Staedtisches Klinikum Braunschweig gGmbH ( Site 1217)
state: Niedersachsen
city: Magdeburg
country: Germany
facility: Universitaetsklinikum Magdeburg A.o.R. ( Site 1211)
state: Sachsen-Anhalt
city: Dresden
country: Germany
facility: Universitaetsklinikum der Technischen Universitaet Dresden ( Site 1204)
state: Sachsen
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin ( Site 1201)
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf ( Site 1212)
city: Cork
country: Ireland
facility: Cork University Hospital ( Site 1304)
city: Dublin
country: Ireland
facility: Beaumont Hospital ( Site 1302)
city: Dublin
country: Ireland
facility: Tallaght University Hospital ( Site 1301)
city: Dublin
country: Ireland
facility: St Vincents University Hospital ( Site 1300)
city: Limerick
country: Ireland
facility: University Hospital Limerick ( Site 1305)
city: Waterford
country: Ireland
facility: University Hospital Waterford ( Site 1303)
city: Haifa
country: Israel
facility: Rambam Medical Center ( Site 1400)
city: Jerusalem
country: Israel
facility: Hadassah Ein Kerem Medical Center ( Site 1404)
city: Kfar Saba
country: Israel
facility: Meir Medical Center ( Site 1401)
city: Petach Tikva
country: Israel
facility: Rabin Medical Center ( Site 1402)
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center ( Site 1403)
city: Zerifin
country: Israel
facility: Assaf Harofeh Medical Center ( Site 1405)
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori ( Site 1503)
state: Emilia-Romagna
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas Research Hospital ( Site 1500)
state: Lombardia
city: Aviano
country: Italy
facility: Centro Di Riferimento Oncologico ( Site 1511)
state: Pordenone
city: Bari
country: Italy
facility: IRCCS Giovanni Paolo II. Ospedale Oncologico ( Site 1509)
city: Catania
country: Italy
facility: Azienda Ospedaliera Cannizzaro ( Site 1501)
city: Milano
country: Italy
facility: Istituto Nazionale dei Tumori ( Site 1510)
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 1508)
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli ( Site 1512)
city: Terni
country: Italy
facility: Azienda Ospedaliera Santa Maria ( Site 1502)
city: Verona
country: Italy
facility: A.O. Verona-Ospedale Civile Maggiore Borgo-Trento ( Site 1504)
city: Sakura
country: Japan
facility: Toho University Sakura Medical Center ( Site 0732)
state: Chiba
city: Toon
country: Japan
facility: Ehime University Hospital ( Site 0745)
state: Ehime
city: Sapporo
country: Japan
facility: Sapporo Medical University Hospital ( Site 0730)
state: Hokkaido
city: Sagamihara
country: Japan
facility: Kitasato University Hospital ( Site 0734)
state: Kanagawa
city: Yokohama
country: Japan
facility: Yokohama City University Medical Center ( Site 0735)
state: Kanagawa
city: Kashihara
country: Japan
facility: Nara Medical University Hospital ( Site 0744)
state: Nara
city: Osakasayama
country: Japan
facility: Kindai University Hospital ( Site 0743)
state: Osaka
city: Suita
country: Japan
facility: Osaka University Hospital ( Site 0742)
state: Osaka
city: Hidaka
country: Japan
facility: Saitama Medical University International Medical Center ( Site 0737)
state: Saitama
city: Koshigaya
country: Japan
facility: Dokkyo Medical University Saitama Medical Center ( Site 0736)
state: Saitama
city: Hamamatsu
country: Japan
facility: Hamamatsu University Hospital ( Site 0748)
state: Shizuoka
city: Ube
country: Japan
facility: Yamaguchi University Hospital ( Site 0746)
state: Yamaguchi
city: Chiba
country: Japan
facility: Chiba Cancer Center ( Site 0733)
city: Fukuoka
country: Japan
facility: Harasanshin Hospital ( Site 0747)
city: Nagano
country: Japan
facility: Nagano Municipal Hospital ( Site 0731)
city: Osaka
country: Japan
facility: Osaka City University Hospital ( Site 0741)
city: Tokyo
country: Japan
facility: Toranomon Hospital ( Site 0740)
city: Tokyo
country: Japan
facility: Nippon Medical School Hospital ( Site 0738)
city: Tokyo
country: Japan
facility: Tokyo Women's Medical University Hospital ( Site 0739)
city: Jeollanam-do
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital ( Site 0406)
state: Jeonranamdo
city: Gyeonggi-do
country: Korea, Republic of
facility: National Cancer Center ( Site 0400)
state: Kyonggi-do
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital ( Site 0401)
state: Kyonggi-do
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital ( Site 0404)
state: Taegu-Kwangyokshi
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital ( Site 0405)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System ( Site 0402)
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center ( Site 0403)
city: Tuxtla Gutierrez
country: Mexico
facility: Hospital San Lucas Cardiologica del Sureste ( Site 2606)
state: Chiapas
city: Guadalajara
country: Mexico
facility: Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 2607)
state: Jalisco
city: Chihuahua
country: Mexico
facility: Centro Estatal de Cancerologia de Chihuahua ( Site 2608)
city: Mexico City
country: Mexico
facility: Grupo Medico Camino SC ( Site 2613)
city: Mexico City
country: Mexico
facility: Centro Oncologico Internacional. SEDNA ( Site 2609)
city: Queretaro
country: Mexico
facility: Boca Raton Clinical Research QTO ( Site 2611)
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center ( Site 1606)
state: Gelderland
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek Ziekenhuis ( Site 1603)
state: Noord-Holland
city: Amsterdam
country: Netherlands
facility: Vrije Universiteit Medisch Centrum ( Site 1601)
state: Noord-Holland
city: Zwolle
country: Netherlands
facility: Isala Klinieken, Locatie Sophia ( Site 1604)
state: Overijssel
city: Amersfoort
country: Netherlands
facility: Meander Medisch Centrum ( Site 1602)
state: Utrecht
city: Schiedam
country: Netherlands
facility: Franciscus Gasthuis en Vlietland ( Site 1605)
state: Zuid-Holland
city: Utrecht
country: Netherlands
facility: St. Antonius Ziekenhuis ( Site 1600)
city: Auckland
country: New Zealand
facility: Auckland City Hospital ( Site 0321)
city: Arequipa
country: Peru
facility: Hospital Nacional Carlos Alberto Seguin Escobedo ESSALUD ( Site 2700)
state: Ariqipa
city: Trujillo
country: Peru
facility: Clinica Peruano Americana S.A. ( Site 2702)
state: La Libertad
city: Lima
country: Peru
facility: Hospital Nacional Guillermo Almenara Irigoyen ( Site 2708)
city: Lima
country: Peru
facility: Instituto de Oncologia y Radioterapia Clinica Ricardo Palma ( Site 2706)
city: Lima
country: Peru
facility: Hospital Militar Central [Lima, Peru] ( Site 2704)
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr 1 im. Dr. Antoniego Jurasza w Bydgoszczy ( Site 1720)
state: Kujawsko-pomorskie
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 1716)
state: Kujawsko-pomorskie
city: Torun
country: Poland
facility: Nasz Lekarz Przychodnie Medyczne ( Site 1718)
state: Kujawsko-pomorskie
city: Krakow
country: Poland
facility: Szpital Uniwersytecki w Krakowie ( Site 1707)
state: Malopolskie
city: Radom
country: Poland
facility: Radomskie Centrum Onkologii ( Site 1701)
state: Mazowieckie
city: Przemysl
country: Poland
facility: Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu ( Site 1700)
state: Podkarpackie
city: Bytom
country: Poland
facility: Wojewodzki Szpital Specjalistyczny nr 4 w Bytomiu ( Site 1717)
state: Slaskie
city: Poznan
country: Poland
facility: Szpital Kliniczny im. Przemienienia Panskiego Uniwersytetu Medycznego im. K. Marcinkowskiego w Pozna
state: Wielkopolskie
city: Koszalin
country: Poland
facility: Szpital Wojewodzki im. Mikolaja Kopernika ( Site 1709)
state: Zachodniopomorskie
city: Szczecin
country: Poland
facility: Twoja Przychodnia - Szczeciskie Centrum Medyczne ( Site 1721)
state: Zachodniopomorskie
city: Krasnoyarsk
country: Russian Federation
facility: Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 1810)
state: Krasnoyarskiy Kray
city: Moscow
country: Russian Federation
facility: SBIH City clinical hospital named after D.D. Pletniov ( Site 1813)
state: Moskva
city: Moscow
country: Russian Federation
facility: Russian Scientific Center of Roentgenoradiology ( Site 1800)
state: Moskva
city: Nizhny Novgorod
country: Russian Federation
facility: Volga District Medical Center Federal Medical and Biological Agency ( Site 1805)
state: Nizhegorodskaya Oblast
city: Omsk
country: Russian Federation
facility: Omsk Clinical Oncology Dispensary ( Site 1809)
state: Omskaya Oblast
city: Hospitalet de Llobregat
country: Spain
facility: Instituto Catalan de Oncologia - ICO ( Site 1901)
state: Barcelona
city: Girona
country: Spain
facility: Hospital Josep Trueta ( Site 1900)
state: Gerona
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti ( Site 1905)
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal ( Site 1902)
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos ( Site 1906)
city: Madrid
country: Spain
facility: Hospital 12 de Octubre de Madrid ( Site 1903)
city: Sevilla
country: Spain
facility: Hospital Virgen de la Macarena ( Site 1904)
city: Chur
country: Switzerland
facility: Kantonsspital Graubuenden ( Site 2003)
state: Grisons
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen ( Site 2000)
state: Sankt Gallen
city: Lausanne
country: Switzerland
facility: CHUV (centre hospitalier universitaire vaudois) ( Site 2002)
state: Vaud
city: Zuerich
country: Switzerland
facility: Universitaetsspital Zuerich ( Site 2001)
state: Zurich
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital ( Site 0504)
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital ( Site 0503)
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital ( Site 0500)
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital ( Site 0501)
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation. Linkou ( Site 0502)
city: Bangkok
country: Thailand
facility: Chulalongkorn Hospital, Medical Oncology Unit ( Site 0600)
state: Krung Thep Maha Nakhon
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital. ( Site 0601)
state: Krung Thep Maha Nakhon
city: Bangkok
country: Thailand
facility: Faculty of Medicine Siriraj Hospital ( Site 0602)
state: Krung Thep Maha Nakhon
city: Khon Kaen
country: Thailand
facility: Srinagarind Hospital ( Site 0604)
city: Adana
country: Turkey
facility: Acibadem Adana Hastanesi ( Site 2106)
city: Ankara
country: Turkey
facility: Ankara Universitesi Tip Fakultesi. ( Site 2101)
city: Ankara
country: Turkey
facility: Hacettepe Universitesi Tıp Fakultesi ( Site 2105)
city: Ankara
country: Turkey
facility: Ankara Sehir Hastanesi ( Site 2103)
city: Istanbul
country: Turkey
facility: Istanbul Uni. Cerrahpasa Tip Fakultesi ( Site 2100)
city: Izmir
country: Turkey
facility: Ege University Medical Faculty Tulay Aktas Oncology Hospital ( Site 2102)
city: Konya
country: Turkey
facility: Konya Necmettin Erbakan University Medical Faculty ( Site 2104)
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary ( Site 1315)
state: Aberdeen City
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospitals NHS Trust ( Site 1317)
state: Cornwall
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust ( Site 1320)
state: London, City Of
city: London
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust ( Site 1318)
state: London, City Of
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre Hospital ( Site 1322)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: