Study of Pembrolizumab (MK-3475) Plus Enzalutamide Versus Placebo Plus Enzalutamide in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-3475-641/KEYNOTE-641)

Prostatic Neoplasms Clinical Trial

Official title:

A Phase 3, Randomized, Double-blind Trial of Pembrolizumab (MK-3475) Plus Enzalutamide Versus Placebo Plus Enzalutamide in Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC) (KEYNOTE-641)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03834493
• Other study ID #: 3475-641
• Secondary ID: MK-3475-641KEYNO
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 28, 2019
• Est. completion date: May 31, 2024

Study information

• Verified date: November 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the efficacy and safety of the combination of pembrolizumab (MK-3475) and enzalutamide in the treatment of men with metastatic castration-resistant prostate cancer (mCRPC) who have not received chemotherapy for mCRPC, are abiraterone-naïve, or are intolerant to or progressed on abiraterone acetate. There are two primary study hypotheses. Hypothesis 1: The combination of pembrolizumab plus enzalutamide is superior to placebo plus enzalutamide with respect to Overall Survival (OS). Hypothesis 2: The combination of pembrolizumab plus enzalutamide is superior to placebo plus enzalutamide with respect to 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1244
• Est. completion date: May 31, 2024
• Est. primary completion date: December 12, 2022
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

• Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
• Has prostate cancer progression while on androgen deprivation therapy (or post bilateral orchiectomy) within 6 months prior to randomization
• Has current evidence of metastatic disease documented by either bone lesions on bone scan and/or soft tissue disease by computed tomography/magnetic resonance imaging (CT/MRI)
• Has met one of the following criteria with regard to abiraterone acetate exposure: (1) is abiraterone-naïve; (2) received prior abiraterone acetate for the treatment of mHSPC or mCRPC, for a minimum of 4 weeks and not progressed while on treatment; or (3) received prior abiraterone acetate for the treatment of mHSPC or mCRPC and progressed on treatment after a minimum of 8 weeks treatment (minimum 14 weeks for those with bone progression)
• Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<2.0 nM)
• Participants receiving bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses prior to randomization
• Participants must agree to the following during the study treatment period and for at least 90 days after the last dose of enzalutamide: Refrain from donating sperm, plus EITHER be abstinent OR must agree to use male condom
• 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
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 7 days of randomization

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 (noninfectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease
• Has known active human immunodeficiency virus (HIV), concurrent active hepatitis B virus (HBV) or known active hepatitis C virus (HCV) infection
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has hypersensitivity to pembrolizumab and/or enzalutamide and/or any of their excipients
• 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 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 bradycardia (heart rate of <50 beats per minute) on the screening electrocardiogram (ECG)
• Has history of prostate cancer progression on ketoconazole
• Has had prior treatment with enzalutamide, apalutamide, darolutamide or cytochrome P450 (CYP) 17 inhibitor other than abiraterone acetate
• 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-PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
• Has received prior treatment with radium or other therapeutic radiopharmaceuticals for prostate cancer
• Has received prior treatment with docetaxel or another chemotherapy agent for mCRPC
• Has had a prior anti-cancer monoclonal antibody (mAb) prior to randomization
• Has used herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (eg, saw palmetto) prior to randomization
• Has received a live or live attenuated vaccine within 30 days prior to randomization
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
• Has a "superscan" bone scan
• Is expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 90 days after the last dose of enzalutamide
• Has had an allogenic tissue/solid organ transplant

Related Conditions & MeSH terms

• Prostatic Neoplasms

Intervention

Biological:
• Pembrolizumab
IV infusion

Drug:
• Enzalutamide
Capsules/Tablets
• Placebo
IV infusion

Locations

Country	Name	City	State
Argentina	Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 1013)	Berazategui	Buenos Aires
Argentina	Centro de Diagnostico Urologico ( Site 1008)	Buenos Aires	Caba
Argentina	Centro Medico Dra De Salvo ( Site 1018)	Buenos Aires
Argentina	Hospital Aleman ( Site 1004)	Buenos Aires
Argentina	Instituto de Investigaciones Metabolicas [Buenos Aires, Argentina] ( Site 1011)	Buenos Aires
Argentina	Instituto Medico Alexander Fleming ( Site 1010)	Buenos Aires	Caba
Argentina	CEMAIC ( Site 1014)	Cordoba
Argentina	Centro Oncologico Riojano Integral ( Site 1005)	La Rioja
Argentina	Instituto de Investigaciones Clinicas ( Site 1000)	Mar del Plata	Buenos Aires
Argentina	Centro Oncologico de Integracion Regional. COIR ( Site 1007)	Mendoza
Argentina	Instituto de Oncologia de Rosario ( Site 1015)	Rosario	Santa Fe
Argentina	Sanatorio Parque ( Site 1002)	Rosario	Santa Fe
Australia	Royal Adelaide Hospital ( Site 0154)	Adelaide	South Australia
Australia	Monash Health-Monash Medical Centre ( Site 0147)	Clayton	Victoria
Australia	St. Vincent's Hospital ( Site 0158)	Darlinghurst	New South Wales
Australia	Gallipoli Medical Research Foundation ( Site 0149)	Greenslopes	Queensland
Australia	St George Hospital ( Site 0157)	Kogarah	New South Wales
Australia	Macquarie University ( Site 0151)	Macquarie University	New South Wales
Australia	Fiona Stanley Hospital ( Site 0162)	Perth	Western Australia
Australia	Port Macquarie Base Hospital ( Site 0153)	Port Macquarie	New South Wales
Australia	Gold Coast University Hospital ( Site 0150)	Southport	Queensland
Australia	Calvary Mater Newcastle ( Site 0148)	Waratah	New South Wales
Austria	Ordensklinikum Linz GmbH Elisabethinen ( Site 0373)	Linz	Oberosterreich
Austria	Medizinische Universität Wien ( Site 0375)	Wien
Brazil	Hospital Erasto Gaertner-CEPEP - Pesquisa Clínica ( Site 1036)	Curitiba	Parana
Brazil	ONCOSITE - Centro de Pesquisa Clinica em Oncologia ( Site 1038)	Ijui	Rio Grande Do Sul
Brazil	Centro de Novos Tratamentos Itajai - Clinica de Neoplasias Litoral ( Site 1035)	Itajai	Santa Catarina
Brazil	Liga Norte Riograndense Contra o Câncer-Centro de Pesquisa Clínica ( Site 1032)	Natal	Rio Grande Do Norte
Brazil	Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 1021)	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital de Base de Sao Jose de Rio Preto ( Site 1022)	Sao Jose do Rio Preto	Sao Paulo
Brazil	A.C. Camargo Cancer Center ( Site 1026)	Sao Paulo
Brazil	Núcleo de Pesquisa Clínica da Rede São Camilo ( Site 1040)	São Paulo	Sao Paulo
Bulgaria	Complex Cancer Center Plovdiv-First Medical Oncology Department ( Site 0507)	Plovdiv
Bulgaria	MHAT Central Hospital ( Site 0503)	Plovdiv
Bulgaria	MHAT Serdika-Second Department of Medical Oncology ( Site 0505)	Sofia	Sofia (stolitsa)
Canada	CISSS de la Monteregie-Centre ( Site 0119)	Greenfield Park	Quebec
Canada	Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0116)	Hamilton	Ontario
Canada	Grand River Hospital ( Site 0120)	Kitchener	Ontario
Canada	Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0106)	Montreal	Quebec
Canada	Lakeridge Health ( Site 0117)	Oshawa	Ontario
Canada	CHUQ-Univ Laval-Hotel Dieu de Quebec ( Site 0103)	Quebec
Canada	CIUSSS du Bas Saint Laurent - Hopital Regional de Rimouski ( Site 0102)	Rimouski	Quebec
Canada	CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 0105)	Sherbrooke	Quebec
Canada	Health Sciences North ( Site 0122)	Sudbury	Ontario
Canada	Princess Margaret Cancer Centre ( Site 0107)	Toronto	Ontario
Canada	Sunnybrook Research Institute ( Site 0108)	Toronto	Ontario
Canada	BC Cancer - Victoria ( Site 0111)	Victoria	British Columbia
Chile	Bradfordhill ( Site 1044)	Santiago	Region M. De Santiago
Chile	Fundacion Arturo Lopez Perez ( Site 1049)	Santiago	Region M. De Santiago
Chile	Pontificia Universidad Catolica de Chile ( Site 1047)	Santiago	Region M. De Santiago
Chile	Centro Investigación del Cáncer James Lind ( Site 1041)	Temuco	Araucania
Chile	Rey y Oreilly Limitada ( Site 1048)	Temuco	Araucania
Chile	Oncocentro ( Site 1045)	Vina del Mar	Valparaiso
Colombia	Biomelab S A S ( Site 1067)	Barranquilla	Atlantico
Colombia	Clinica de la Costa Ltda. ( Site 1073)	Barranquilla	Atlantico
Colombia	Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 1062)	Bogota	Distrito Capital De Bogota
Colombia	Centro Medico Imbanaco de Cali S.A ( Site 1064)	Cali	Valle Del Cauca
Colombia	Hemato Oncologos S.A. ( Site 1065)	Cali	Valle Del Cauca
Colombia	Hospital Pablo Tobon Uribe ( Site 1066)	Medellin	Antioquia
Colombia	Oncomedica S.A. ( Site 1057)	Monteria	Cordoba
Colombia	Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 1068)	Valledupar	Cesar
Czechia	Fakultni Nemocnice u sv. Anny v Brne-Onkologicko-chirurgicke oddeleni ( Site 1303)	Brno	Brno-mesto
Czechia	Nemocnice AGEL Novy Jicin a.s. ( Site 1304)	Nový Jicín	Novy Jicin
Czechia	Fakultni nemocnice Olomouc ( Site 1301)	Olomouc
France	CHU Amiens Picardie Site Sud Amiens ( Site 0438)	Amiens	Somme
France	Institut Sainte Catherine ( Site 0447)	Avignon	Vaucluse
France	CHU Jean Minjoz ( Site 0423)	Besancon	Doubs
France	Institut Bergonie ( Site 0421)	Bordeaux	Gironde
France	CHU de Brest -Site Hopital Morvan ( Site 0441)	Brest	Bretagne
France	Centre Jean Perrin ( Site 0434)	Clermont-Ferrand	Auvergne
France	Institut Regional du Cancer de Montpellier - ICM ( Site 0443)	Montpellier	Herault
France	Centre D Oncologie de Gentilly ( Site 0432)	Nancy	Meurthe-et-Moselle
France	Centre Hospitalier Regional du Orleans ( Site 0430)	Orleans	Loiret
France	Institut Mutualiste Montsouris ( Site 0446)	Paris
France	C.H.U. Lyon Sud ( Site 0436)	Pierre Benite	Rhone
France	Institut De Cancerologie De L Ouest ( Site 0448)	Saint Herblain	Loire-Atlantique
France	C.H. de Saint Quentin ( Site 0481)	Saint Quentin	Aisne
France	Clinique Sainte Anne ( Site 0431)	Strasbourg	Alsace
France	Hopital Foch ( Site 0428)	Suresnes	Hauts-de-Seine
France	Institut Claudius Regaud IUCT Oncopole ( Site 0418)	Toulouse	Haute-Garonne
France	Centre Hospitalier de Valenciennes ( Site 0439)	Valenciennes	Nord
France	Institut Gustave Roussy ( Site 0416)	Villejuif	Val-de-Marne
Germany	Uniklinik RWTH Aachen ( Site 0308)	Aachen	Nordrhein-Westfalen
Germany	Charite Universitaetsmedizin Berlin ( Site 0301)	Berlin
Germany	Universitaetsklinikum Freiburg - Medizinische Klinik ( Site 0304)	Freiburg	Baden-Wurttemberg
Germany	Universitaetsklinikum Goettingen ( Site 0345)	Goettingen	Niedersachsen
Germany	Universitaetsklinikum des Saarlandes ( Site 0348)	Homburg	Saarland
Germany	Universitaetsklinikum Jena ( Site 0305)	Jena	Thuringen
Germany	Universitaetsklinikum Schleswig Holstein. ( Site 0346)	Luebeck	Schleswig-Holstein
Germany	Klinikum Rechts der Isar ( Site 0300)	Muenchen	Bayern
Germany	Universitaetsklinikum Muenster ( Site 0320)	Muenster	Nordrhein-Westfalen
Germany	Universitaetsklinik der Paracelsus Medizinischen Privatuniversitaet ( Site 0318)	Nuernberg	Bayern
Germany	Studienpraxis Urologie ( Site 0309)	Nuertingen	Baden-Wurttemberg
Germany	Krankenhaus der Barmherzigen Brueder Trier ( Site 0310)	Trier	Rheinland-Pfalz
Germany	Universitaetsklinik fuer Urologie ( Site 0307)	Tuebingen	Baden-Wurttemberg
Hungary	Magyar Honvedseg Egeszsegugyi Kozpont-Onkologiai Osztaly ( Site 1326)	Budapest
Hungary	Országos Onkológiai Intézet-Urogenital Tumors Department and Clinical Pharmacology ( Site 1325)	Budapest	Pest
Hungary	Petz Aladár Megyei Oktató Kórház-Onkológiai Osztály ( Site 1324)	Gyor	Gyor-Moson-Sopron
Hungary	Bacs-Kiskun Megyei Korhaz-Onkoradiologiai Kozpont ( Site 1321)	Kecskemét	Bacs-Kiskun
Ireland	Beaumont Hospital ( Site 0726)	Dublin
Ireland	Tallaght University Hospital ( Site 0730)	Dublin
Ireland	Mid Western Cancer Centre ( Site 0728)	Limerick
Israel	HaEmek Medical Center ( Site 0548)	Afula
Israel	Assuta Ashdod Medical Center ( Site 0550)	Ashdod
Israel	Soroka Medical Center ( Site 0549)	Beer Sheva
Israel	Rambam Health Care Campus-Oncology Division ( Site 0543)	Haifa
Israel	Hadassah Ein Kerem Medical Center ( Site 0546)	Jerusalem
Israel	Meir Medical Center ( Site 0544)	Kfar Saba
Israel	Rabin Medical Center ( Site 0545)	Petach-Tikwa
Israel	Chaim Sheba Medical Center ( Site 0541)	Ramat Gan
Israel	Sourasky Medical Center ( Site 0542)	Tel Aviv
Israel	Yitzhak Shamir Medical Center ( Site 0547)	Zerifin
Italy	Medical Oncology Ospedale San Donato ( Site 0461)	Arezzo
Italy	Centro Di Riferimento Oncologico ( Site 0800)	Aviano	Pordenone
Italy	Ospedale Policlinico S. Orsola-Malpighi ( Site 0453)	Bologna
Italy	Azienda Ospedaliera Cannizzaro ( Site 0458)	Catania
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori-Oncologia Medica ( Site 0464)	Meldola	Emilia-Romagna
Italy	A.O. Universitaria di Modena ( Site 0454)	Modena
Italy	Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 0462)	Napoli
Italy	Presidio Ospedaliero S. Maria Delle Grazie-U.O.C. ONCOLOGIA ( Site 0802)	Pozzuoli	Napoli
Italy	Azienda Ospedaliera San Camillo Forlanini ( Site 0455)	Roma
Italy	Fondazione Policlinico Universitario Agostino Gemelli ( Site 0801)	Roma
Italy	Istituto Clinico Humanitas Research Hospital ( Site 0452)	Rozzano	Lombardia
Italy	Azienda Ospedaliera Santa Maria Terni ( Site 0456)	Terni
Italy	Az. Osp. Univ. Sta Maria della Misericordia di Udine ( Site 0460)	Udine
Italy	Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Roma-Oncology Unit ( Site 0465)	Verona	Veneto
Japan	Chiba Cancer Center ( Site 0704)	Chiba
Japan	Kyushu University Hospital ( Site 0718)	Fukuoka
Japan	Hakodate Goryoukaku Hospital ( Site 0739)	Hakodate	Hokkaido
Japan	Hamamatsu University Hospital ( Site 0720)	Hamamatsu	Shizuoka
Japan	Saitama Medical University International Medical Center ( Site 0708)	Hidaka	Saitama
Japan	Hiroshima Prefectural Hospital ( Site 0748)	Hiroshima
Japan	Iizuka Hospital ( Site 0744)	Iizuka	Fukuoka
Japan	Kanazawa University Hospital ( Site 0701)	Kanazawa	Ishikawa
Japan	Nara Medical University Hospital ( Site 0715)	Kashihara	Nara
Japan	National Cancer Center Hospital East ( Site 0702)	Kashiwa	Chiba
Japan	Saitama Medical Center ( Site 0743)	Kawagoe	Saitama
Japan	Dokkyo Medical University Saitama Medical Center ( Site 0707)	Koshigaya	Saitama
Japan	National Hospital Organization Shikoku Cancer Center ( Site 0716)	Matsuyama	Ehime
Japan	University of Miyazaki Hospital ( Site 0721)	Miyazaki
Japan	Nagasaki University Hospital ( Site 0719)	Nagasaki
Japan	Miyagi Cancer Center ( Site 0747)	Natori	Miyagi
Japan	Kindai University Hospital ( Site 0714)	Osakasayama	Osaka
Japan	Kitasato University Hospital ( Site 0705)	Sagamihara	Kanagawa
Japan	Toho University Sakura Medical Center ( Site 0703)	Sakura	Chiba
Japan	Osaka University Hospital ( Site 0713)	Suita	Osaka
Japan	Keio University Hospital ( Site 0710)	Tokyo
Japan	Nippon Medical School Hospital ( Site 0709)	Tokyo
Japan	Toranomon Hospital ( Site 0711)	Tokyo
Japan	Yamaguchi University Hospital ( Site 0717)	Ube	Yamaguchi
Japan	Yokohama City University Medical Center ( Site 0706)	Yokohama	Kanagawa
Korea, Republic of	National Cancer Center ( Site 0174)	Goyang-si	Kyonggi-do
Korea, Republic of	Seoul National University Bundang Hospital ( Site 0175)	Seongnam-si	Kyonggi-do
Korea, Republic of	Samsung Medical Center ( Site 0172)	Seoul
Korea, Republic of	Seoul National University Hospital ( Site 0171)	Seoul
Korea, Republic of	Asan Medical Center ( Site 0176)	Songpagu	Seoul
Netherlands	Noordwest Ziekenhuisgroep NWZ ( Site 0468)	Alkmaar	Noord-Holland
Netherlands	Vrije Universiteit Medisch Centrum ( Site 0479)	Amsterdam	Noord-Holland
Netherlands	Amphia Hospital Location Molengracht ( Site 0474)	Breda	Noord-Brabant
Netherlands	Catharina Ziekenhuis ( Site 0472)	Eindhoven	Noord-Brabant
Netherlands	Ziekenhuisgroep Twente ( Site 0469)	Hengelo	Overijssel
Netherlands	Tergooiziekenhuizen ( Site 0466)	Hilversum	Noord-Holland
Netherlands	Spaarne Ziekenhuis ( Site 0473)	Hoofddorp	Noord-Holland
Netherlands	Haaglanden MC - locatie Antoniushove ( Site 0471)	Leidschendam	Zuid-Holland
Netherlands	Maastricht University Medical Centre ( Site 0467)	Maastricht	Limburg
Netherlands	Radboud University Medical Center ( Site 0470)	Nijmegen	Gelderland
Netherlands	Franciscus Gasthuis en Vlietland ( Site 0489)	Schiedam	Zuid-Holland
New Zealand	Auckland City Hospital ( Site 0193)	Auckland
New Zealand	Canterbury Regional Cancer & Blood Service ( Site 0195)	Christchurch	Canterbury
New Zealand	Tauranga Hospital ( Site 0215)	Tauranga	Bay Of Plenty
Poland	Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 0636)	Bydgoszcz	Kujawsko-pomorskie
Poland	Przychodnia Lekarska Komed ( Site 0628)	Konin	Wielkopolskie
Poland	Szpital Wojewodzki im. Mikolaja Kopernika ( Site 0624)	Koszalin	Zachodniopomorskie
Poland	Salve Medica SP ( Site 0686)	Lodz	Lodzkie
Poland	Provita Prolife Centrum Medyczne ( Site 0630)	Tomaszow Mazowiecki	Lodzkie
Poland	Clinical Best Solutions ( Site 0622)	Warszawa	Mazowieckie
Puerto Rico	Fundacion de Investigacion de Diego ( Site 1121)	San Juan
Puerto Rico	Puerto Rico Medical Research Center LLC ( Site 1122)	San Juan
Russian Federation	Chelyabinsk Regional Clinical Oncological Dispensary ( Site 0565)	Chelyabinsk	Chelyabinskaya Oblast
Russian Federation	Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 0585)	Krasnoyarsk	Krasnoyarskiy Kray
Russian Federation	Central Clinical Hospital with Polyclinic ( Site 0562)	Moscow	Moskva
Russian Federation	Russian Scientific Center of Roentgenoradiology ( Site 0559)	Moscow	Moskva
Russian Federation	Omsk Clinical Oncology Dispensary ( Site 0568)	Omsk	Omskaya Oblast
Russian Federation	Clinical Research Center of specialized types medical care-Oncology ( Site 0570)	Saint Petersburg	Sankt-Peterburg
Russian Federation	Russian Scientific Center of Radiology and Surgical Technologies ( Site 0567)	Saint Petersburg	Sankt-Peterburg
Russian Federation	SBHI Leningrad Regional Oncology Dispensary ( Site 0588)	Saint Petersburg	Sankt-Peterburg
Russian Federation	SBHI Samara Regional Clinical Oncology Dispensary ( Site 0576)	Samara	Samarskaya Oblast
Russian Federation	Tomsk National Scientific Medical Center of Russian Academy of Science ( Site 0579)	Tomsk	Tomskaya Oblast
Spain	Hospital del Mar ( Site 0333)	Barcelona
Spain	Hospital Provincial San Pedro Alcantara ( Site 0326)	Caceres
Spain	Hospital Josep Trueta ( Site 0321)	Girona	Gerona
Spain	Instituto Catalan de Oncologia - ICO ( Site 0330)	L Hospitalet De Llobregat	Barcelona
Spain	Hospital Clinico San Carlos ( Site 0324)	Madrid
Spain	Hospital Universitario Gregorio Maranon ( Site 0327)	Madrid
Spain	Hospital Universitario HM Sanchinarro ( Site 0322)	Madrid
Spain	MD Anderson Cancer Center Madrid ( Site 0332)	Madrid
Spain	Hospital Universitario Virgen de la Victoria ( Site 0337)	Malaga
Spain	Hospital Quiron Madrid ( Site 0325)	Pozuelo de Alarcon	Madrid
Spain	Hospital Parc Tauli ( Site 0335)	Sabadell	Barcelona
Spain	Hospital Virgen del Rocio ( Site 0329)	Sevilla
Spain	Instituto Valenciano de Oncologia ( Site 0331)	Valencia	Valenciana, Comunitat
Taiwan	China Medical University Hospital ( Site 0132)	Taichung
Taiwan	Taichung Veterans General Hospital ( Site 0133)	Taichung
Taiwan	National Cheng Kung University Hospital ( Site 0134)	Tainen	Tainan
Taiwan	National Taiwan University Hospital ( Site 0131)	Taipei
Taiwan	Taipei Veterans General Hospital ( Site 0135)	Taipei
Turkey	Baskent University Dr. Turgut Noyan Research and Training Center-ONCCOLOGY ( Site 0618)	Adana
Turkey	Ankara City Hospital-Medical Oncology ( Site 0616)	Ankara
Turkey	Ankara University Hospital Cebeci ( Site 0613)	Ankara
Turkey	Hacettepe Universitesi-oncology hospital ( Site 0615)	Ankara
Turkey	Ege University Medicine of Faculty ( Site 0661)	Bornova	Izmir
Turkey	Acibadem Maslak Hastanesi ( Site 0660)	Istanbul
Turkey	T.C. Saglik Bakanligi Turkiye Kamu Hastaneleri Kurumu - Baki-Istanbul Bakirkoy Sadi Konuk Training (	Istanbul
Turkey	TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 0619)	Istanbul
Ukraine	Cherkasy Regional Oncology Dispensary ( Site 1203)	Cherkassy	Cherkaska Oblast
Ukraine	Dnepropetrovsk Regional Clinical Hospital Mechnikov-Department of urology ( Site 1205)	Dnipro	Dnipropetrovska Oblast
Ukraine	Dnepropetrovsk Regional Clinical Oncology Hospital-Clinical oncological dispensary ( Site 1201)	Dnipropetrovsk	Dnipropetrovska Oblast
Ukraine	Communal Non-Commercial Enterprise ""Prykarpatski Clinical Oncological Center"" of Ivano-Frankivsk R	Ivano-Frankivsk	Ivano-Frankivska Oblast
Ukraine	Ivano-Frankivsk Regional Hospital-Urology department ( Site 1208)	Ivano-Frankivsk	Ivano-Frankivska Oblast
Ukraine	CNPE Regional Center of Oncology-oncourology department ( Site 1202)	Kharkiv	Kharkivska Oblast
Ukraine	LISOD - Israeli Oncological Hospital ""MedX-ray Internationa-Department of Clinical and Scientific (	Kiev	Kyivska Oblast
Ukraine	Municipal non-profit enterprise Kyiv City Clinical Oncology -Oncourology department ( Site 1204)	Kyiv	Kyivska Oblast
United Kingdom	University Hospitals Bristol NHS Foundation Trust ( Site 0530)	Bristol	Bristol, City Of
United Kingdom	Cambridge University Hospitals NHS Trust ( Site 0540)	Cambridge	Cambridgeshire
United Kingdom	Western General Hospital ( Site 0531)	Edinburgh	Worcestershire
United Kingdom	Royal Marsden Hospital (Sutton) ( Site 0526)	London	Sutton
United Kingdom	University College London Hospitals NHS Foundation Trust ( Site 0482)	London	London, City Of
United Kingdom	Mount Vernon Cancer Centre ( Site 0536)	Northwood
United Kingdom	Musgrove Park Hospital ( Site 0537)	Taunton	Somerset
United Kingdom	Torbay Hospital ( Site 0532)	Torquay	Devon
United States	Georgia Cancer Center at Augusta University ( Site 0026)	Augusta	Georgia
United States	University of Colorado Cancer Center ( Site 0022)	Aurora	Colorado
United States	St. Vincent Frontier Cancer Center ( Site 0016)	Billings	Montana
United States	Gabrail Cancer Center-Research ( Site 0096)	Canton	Ohio
United States	Mount Sinai Hospital Medical Center ( Site 0042)	Chicago	Illinois
United States	Tri-State Urologic Services PSC, Inc. ( Site 0094)	Cincinnati	Ohio
United States	University Hospitals Cleveland Medical Center ( Site 0036)	Cleveland	Ohio
United States	Inova Schar Cancer Institute ( Site 0006)	Fairfax	Virginia
United States	St. Joseph Heritage Healthcare ( Site 0069)	Fullerton	California
United States	Cancer & Hematology Centers of Western Michigan ( Site 0013)	Grand Rapids	Michigan
United States	John Theurer Cancer Center at Hackensack University Medical Center ( Site 0004)	Hackensack	New Jersey
United States	Comprehensive Cancer Centers of Nevada ( Site 0092)	Las Vegas	Nevada
United States	UCLA Hematology/Oncology - Santa Monica ( Site 0081)	Los Angeles	California
United States	Methodist Hospitals. ( Site 0008)	Merrillville	Indiana
United States	Froedtert Hospital & the Medical College of Wisconsin ( Site 0045)	Milwaukee	Wisconsin
United States	University of South Alabama, Mitchell Cancer Institute ( Site 0065)	Mobile	Alabama
United States	Carolina Urologic Research Center ( Site 0070)	Myrtle Beach	South Carolina
United States	Smilow Cancer Hospital at Yale New Haven ( Site 0038)	New Haven	Connecticut
United States	Tulane Cancer Center ( Site 0066)	New Orleans	Louisiana
United States	Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0034)	Omaha	Nebraska
United States	Oregon Health Sciences University ( Site 0031)	Portland	Oregon
United States	Virginia Cancer Institute ( Site 0052)	Richmond	Virginia
United States	Blue Ridge Cancer Care ( Site 0086)	Roanoke	Virginia
United States	W. G. Bill Hefner VA Medical Center ( Site 0029)	Salisbury	North Carolina
United States	Associated Medical Professionals of NY ( Site 0060)	Syracuse	New York
United States	Moffitt Cancer Center ( Site 0080)	Tampa	Florida
United States	Munson Medical Center ( Site 0030)	Traverse City	Michigan
United States	University of Massachusetts Worcester ( Site 0053)	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Brazil,  Bulgaria,  Canada,  Chile,  Colombia,  Czechia,  France,  Germany,  Hungary,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  New Zealand,  Poland,  Puerto Rico,  Russian Federation,  Spain,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	OS was defined as the time from randomization to death due to any cause. The OS for all participants is presented.	Up to 40 months (through database cut-off date of 12-Dec-2022)
Primary	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	rPFS was defined as the time from randomization to the first documented progressive disease (PD) per PCWG-modified RECIST 1.1 based on blinded independent central review or death due to any cause, whichever occurred first. The rPFS per PCWG-modified RECIST for all participants is presented.	Up to 40 months (through database cut-off date of 12-Dec-2022)
Secondary	Time to Initiation of the First Subsequent Anti-cancer Therapy or Death (TFST)	TFST was defined as time from randomization to initiation of the first subsequent anti-cancer therapy or death, whichever occurs first. The TFST for all participants is presented.	Up to 40 months (through database cut-off date of 12-Dec-2022)
Secondary	Prostate-specific Antigen (PSA) Response Rate	PSA response rate was defined as percentage of participants in the analysis population who have a negative change (decrease) in PSA level of =50% measured twice =3 weeks apart. The analysis was performed on participants who had baseline PSA measurements.	Up to 40 months (through database cut-off date of 12-Dec-2022)
Secondary	Prostate-specific Antigen (PSA) Undetectable Rate	PSA undetectable rate was defined as percentage of participants in the analysis population with PSA <0.2 ng/mL during study treatment. The analysis was performed on participants who had baseline PSA measurements.	Up to 40 months (through database cut-off date of 12-Dec-2022)
Secondary	Objective Response (OR) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by as Assessed by Blinded Independent Central Review	OR was defined as the percentage of participants with complete response (CR: disappearance of all target lesions per RECIST 1.1; and no evidence of disease (NED) on bone scan per PCWG) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions per RECIST 1.1; and non-progressive disease, non-evaluable [NE], or NED on bone scan or CR with non-progressive disease or NE bone scan per PCWG).	Up to 40 months (through database cut-off date of 12-Dec-2022)
Secondary	Duration of Response (DOR) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by as Assessed by Blinded Independent Central Review	DOR was defined as the time from first documented evidence of complete response (CR) or partial response (PR) per PCWG and RECIST 1.1 criteria until progressive disease (PD) or death. PD per RECIST 1.1 was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. PD per PCWG was the appearance of =2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and were persistent for =6 weeks. The DOR was calculated using the product-limit (Kaplan-Meier) method for censored data. If a participant had not progressed, the participant was censored at the date of last disease assessment.	Up to 40 months (through database cut-off date of 12-Dec-2022)
Secondary	Time to Prostate-specific Antigen (PSA) Progression	Time from randomization to PSA progression. PSA progression date is defined as the date of 1) =25% increase and =2 ng/mL above the nadir, confirmed by a second value =3 weeks later if there is PSA decline from baseline, or 2) =25% increase and =2 ng/mL increase from baseline beyond 12 weeks if there is no PSA decline from baseline.	Up to 40 months (through database cut-off date of 12-Dec-2022)
Secondary	Time to Radiographic Soft Tissue Progression Per Soft Tissue Rules of Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by as Assessed by Blinded Independent Central Review	Time from randomization to radiographic soft tissue progression per PCWG-modified RECIST 1.1	Up to 40 months (through database cut-off date of 12-Dec-2022)
Secondary	Time to Pain Progression (TTPP) as Assessed by Brief Pain Inventory-Short Form (BPI-SF) Item 3 ("Worst Pain in 24 Hours") and Opiate Analgesic Use (Analgesic Quantification Algorithm [AQA] Score)	Time from randomization to pain progression. In this study, pain progression was assessed by participant responses to Item 3 of the BPI-SF and participant AQA Scores which are both assessed by participants daily for 7 consecutive days.	Up to 40 months (through database cut-off date of 12-Dec-2022)
Secondary	Time to First Symptomatic Skeletal-related Event (SSRE)	Time from randomization to the first SSRE. SSRE is defined as radiation to prevent or relieve skeletal symptoms, occurrence of new symptomatic pathological fracture, spinal cord compression, or surgery to bone.	Up to 40 months (through database cut-off date of 12-Dec-2022)
Secondary	Number of Participants Who Experience an Adverse Event (AE)	An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality. The number of participants who experienced an AE is presented.	Up to 40 months (through database cut-off date of 12-Dec-2022)
Secondary	Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)	An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality. The number of participants who discontinued study treatment due to an AE is presented.	Up to 40 months (through database cut-off date of 12-Dec-2022)

External Links

•   Merck Oncology Clinical Trial Information
•   Plain Language Summary