Metastatic Hormone-Sensitive Prostate Cancer Clinical Trial
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)
| Verified date | November 2023 |
| Source | Merck Sharp & Dohme LLC |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Active, not recruiting |
| Enrollment | 1251 |
| Est. completion date | February 2, 2026 |
| Est. primary completion date | October 31, 2022 |
| Accepts healthy volunteers | No |
| Gender | Male |
| Age group | 18 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Box Hill Hospital ( Site 0304) | Box Hill | Victoria |
| Australia | Chris OBrien Lifehouse ( Site 0300) | Camperdown | New South Wales |
| Australia | Monash Health ( Site 0305) | Clayton | Victoria |
| Australia | Gallipoli Medical Research Foundation ( Site 0309) | Greenslopes | Queensland |
| Australia | Peter MacCallum Cancer Centre ( Site 0306) | Melbourne | Victoria |
| Australia | Fiona Stanley Hospital ( Site 0311) | Murdoch | Western Australia |
| Australia | Port Macquarie Base Hospital ( Site 0301) | Port Macquarie | New South Wales |
| Australia | John Flynn Hospital & Medical Centre ( Site 0308) | Tugun | Queensland |
| Australia | Riverina Cancer Care Center ( Site 0302) | Wagga Wagga | New South Wales |
| Austria | Ordensklinikum Linz GmbH Elisabethinen ( Site 0901) | Linz | Oberosterreich |
| Austria | Landeskrankenhaus Salzburg - Universitatklinikum der PMU ( Site 0900) | Salzburg | |
| Austria | Krankenhaus der Barmherzigen Brüder Wien ( Site 0904) | Wien | |
| Austria | Medizinische Universitaet Wien ( Site 0903) | Wien | |
| Brazil | Clinica de Oncologia Reichow ( Site 2308) | Blumenau | Santa Catarina |
| Brazil | Instituto de Cancer e Transplante de Curitiba ICTR ( Site 2306) | Curitiba | Parana |
| Brazil | Oncocentro Ceara ( Site 2309) | Fortaleza | Ceara |
| Brazil | Fundacao Dr Amaral Carvalho ( Site 2302) | Jau | Sao Paulo |
| Brazil | Hospital Sao Vicente de Paulo ( Site 2303) | Passo Fundo | Rio Grande Do Sul |
| Brazil | Hospital de Clinicas de Porto Alegre ( Site 2304) | Porto Alegre | Rio Grande Do Sul |
| Brazil | Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 2305) | Sao Paulo | |
| Canada | CISSS de la Monteregie-Centre ( Site 0105) | Greenfield Park | Quebec |
| Canada | Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0109) | Montreal | Quebec |
| Canada | CIUSSS Ouest de l Ile - St-Mary s Hospital ( Site 0106) | Montreal | Quebec |
| Canada | The Ottawa Hospital ( Site 0100) | Ottawa | Ontario |
| Canada | CHUQ-Univ Laval-Hotel Dieu de Quebec ( Site 0101) | Quebec | |
| Canada | Niagara Health System - St. Catharines ( Site 0107) | St. Catharines | Ontario |
| Chile | IC La Serena Research ( Site 2406) | La Serena | Coquimbo |
| Chile | Clinica Alemana ( Site 2408) | Santiago | Region M. De Santiago |
| Chile | Pontificia Universidad Catolica de Chile ( Site 2402) | Santiago | Region M. De Santiago |
| Chile | Sociedad Medica Aren y Bachero Limitada ( Site 2403) | Santiago | Region M. De Santiago |
| Chile | Clinica Universidad Catolica del Maule ( Site 2407) | Talca | Maule |
| Chile | Centro Investigación del Cáncer James Lind ( Site 2401) | Temuco | Araucania |
| Chile | Oncocentro ( Site 2400) | Vina del Mar | Valparaiso |
| China | Peking University First Hospital ( Site 0800) | Beijing | Beijing |
| China | Zhejiang Provincial People's Hospital ( Site 0809) | Hangzhou | Zhejiang |
| China | The First Affiliated Hospital of Wenzhou Medical University ( Site 0834) | Wenzhou | Zhejiang |
| Colombia | Institucion Prestadora de Servicios de Salud Clinica de la Costa LTDA ( Site 2504) | Barranquilla | Atlantico |
| Colombia | Administradora Country SA - Clinica del Country ( Site 2507) | Bogota | Distrito Capital De Bogota |
| Colombia | Instituto Nacional de Cancerologia E.S.E ( Site 2506) | Bogota | Distrito Capital De Bogota |
| Colombia | Hemato Oncologos ( Site 2503) | Cali | Valle Del Cauca |
| Colombia | Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 2509) | Valledupar | Cesar |
| Denmark | Aalborg Universitetshospital ( Site 1000) | Aalborg | Nordjylland |
| Denmark | Rigshospitalet ( Site 1005) | Copenhagen | Hovedstaden |
| Denmark | Herlev og Gentofte Hospital. ( Site 1004) | Herlev | Hovedstaden |
| Denmark | Odense Universitetshospital ( Site 1003) | Odense | Syddanmark |
| Denmark | Vejle Sygehus ( Site 1002) | Vejle | Syddanmark |
| Finland | HYKS ( Site 1020) | Helsinki | Varsinais-Suomi |
| Finland | Keski-Suomen keskussairaala ( Site 1017) | Jyvaskyla | Mellersta Finland |
| Finland | Tampereen yliopistollinen sairaala ( Site 1022) | Tampere | Pirkanmaa |
| Finland | TYKS T-sairaala Syopatautien pkl ( Site 1019) | Turku | Varsinais-Suomi |
| France | CHU-Jean Minjoz ( Site 1101) | Besancon | Doubs |
| France | Institut Bergonie ( Site 1104) | Bordeaux | Gironde |
| France | CHU de Brest -Site Hopital Morvan ( Site 1103) | Brest | Bretagne |
| France | Hopital Henri Mondor ( Site 1116) | Creteil | Val-de-Marne |
| France | Centre Georges Francois Leclerc ( Site 1112) | Dijon | Cote-d Or |
| France | Centre Bourgogne ( Site 1119) | Lille | Nord-Pas-de-Calais |
| France | Centre Leon-Berard ( Site 1110) | Lyon | Auvergne |
| France | Centre D Oncologie de Gentilly ( Site 1107) | Nancy | Meurthe-et-Moselle |
| France | Hospices Civils de Lyon Centre Hospitalier Lyon Sud ( Site 1102) | Pierre Benite | Rhone |
| France | Institut Jean Godinot-Clinical Research Unit ( Site 1118) | Reims | Marne |
| France | C.H.R.U. de Rennes. Hopital de Pontchaillou ( Site 1117) | Rennes | Ille-et-Vilaine |
| France | Institut de cancérologie Strasbourg Europe (ICANS) ( Site 1114) | Strasbourg | Bas-Rhin |
| France | Hopital Foch ( Site 1105) | Suresnes | Hauts-de-Seine |
| Germany | Charite Universitaetsmedizin Berlin ( Site 1201) | Berlin | |
| Germany | Staedtisches Klinikum Braunschweig gGmbH ( Site 1217) | Braunschweig | Niedersachsen |
| Germany | Universitaetsklinikum der Technischen Universitaet Dresden ( Site 1204) | Dresden | Sachsen |
| Germany | Universitaetsklinikum Freiburg ( Site 1200) | Freiburg | Baden-Wurttemberg |
| Germany | Universitaetsklinikum Hamburg-Eppendorf ( Site 1212) | Hamburg | |
| Germany | Universitaetsklinikum Magdeburg A.o.R. ( Site 1211) | Magdeburg | Sachsen-Anhalt |
| Germany | Klinikum der Universitaet Muenchen - Grosshadern ( Site 1210) | Muenchen | Bayern |
| Germany | Klinikum Rechts der Isar ( Site 1206) | Munchen | Bayern |
| Germany | Klinikum Nuernberg Nord ( Site 1213) | Nurnberg | Bayern |
| Ireland | Cork University Hospital ( Site 1304) | Cork | |
| Ireland | Beaumont Hospital ( Site 1302) | Dublin | |
| Ireland | St Vincents University Hospital ( Site 1300) | Dublin | |
| Ireland | Tallaght University Hospital ( Site 1301) | Dublin | |
| Ireland | University Hospital Limerick ( Site 1305) | Limerick | |
| Ireland | University Hospital Waterford ( Site 1303) | Waterford | |
| Israel | Rambam Medical Center ( Site 1400) | Haifa | |
| Israel | Hadassah Ein Kerem Medical Center ( Site 1404) | Jerusalem | |
| Israel | Meir Medical Center ( Site 1401) | Kfar Saba | |
| Israel | Rabin Medical Center ( Site 1402) | Petach Tikva | |
| Israel | Sourasky Medical Center ( Site 1403) | Tel Aviv | |
| Israel | Assaf Harofeh Medical Center ( Site 1405) | Zerifin | |
| Italy | Centro Di Riferimento Oncologico ( Site 1511) | Aviano | Pordenone |
| Italy | IRCCS Giovanni Paolo II. Ospedale Oncologico ( Site 1509) | Bari | |
| Italy | Azienda Ospedaliera Cannizzaro ( Site 1501) | Catania | |
| Italy | Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori ( Site 1503) | Meldola | Emilia-Romagna |
| Italy | Istituto Nazionale dei Tumori ( Site 1510) | Milano | |
| Italy | Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 1508) | Napoli | |
| Italy | Fondazione Policlinico Universitario A. Gemelli ( Site 1512) | Roma | |
| Italy | Istituto Clinico Humanitas Research Hospital ( Site 1500) | Rozzano | Lombardia |
| Italy | Azienda Ospedaliera Santa Maria ( Site 1502) | Terni | |
| Italy | A.O. Verona-Ospedale Civile Maggiore Borgo-Trento ( Site 1504) | Verona | |
| Japan | Chiba Cancer Center ( Site 0733) | Chiba | |
| Japan | Harasanshin Hospital ( Site 0747) | Fukuoka | |
| Japan | Hamamatsu University Hospital ( Site 0748) | Hamamatsu | Shizuoka |
| Japan | Saitama Medical University International Medical Center ( Site 0737) | Hidaka | Saitama |
| Japan | Nara Medical University Hospital ( Site 0744) | Kashihara | Nara |
| Japan | Dokkyo Medical University Saitama Medical Center ( Site 0736) | Koshigaya | Saitama |
| Japan | Nagano Municipal Hospital ( Site 0731) | Nagano | |
| Japan | Osaka City University Hospital ( Site 0741) | Osaka | |
| Japan | Kindai University Hospital ( Site 0743) | Osakasayama | Osaka |
| Japan | Kitasato University Hospital ( Site 0734) | Sagamihara | Kanagawa |
| Japan | Toho University Sakura Medical Center ( Site 0732) | Sakura | Chiba |
| Japan | Sapporo Medical University Hospital ( Site 0730) | Sapporo | Hokkaido |
| Japan | Osaka University Hospital ( Site 0742) | Suita | Osaka |
| Japan | Nippon Medical School Hospital ( Site 0738) | Tokyo | |
| Japan | Tokyo Women's Medical University Hospital ( Site 0739) | Tokyo | |
| Japan | Toranomon Hospital ( Site 0740) | Tokyo | |
| Japan | Ehime University Hospital ( Site 0745) | Toon | Ehime |
| Japan | Yamaguchi University Hospital ( Site 0746) | Ube | Yamaguchi |
| Japan | Yokohama City University Medical Center ( Site 0735) | Yokohama | Kanagawa |
| Korea, Republic of | Kyungpook National University Chilgok Hospital ( Site 0404) | Daegu | Taegu-Kwangyokshi |
| Korea, Republic of | National Cancer Center ( Site 0400) | Gyeonggi-do | Kyonggi-do |
| Korea, Republic of | Chonnam National University Hwasun Hospital ( Site 0406) | Jeollanam-do | Jeonranamdo |
| Korea, Republic of | Seoul National University Bundang Hospital ( Site 0401) | Seongnam-si | Kyonggi-do |
| Korea, Republic of | Asan Medical Center ( Site 0403) | Seoul | |
| Korea, Republic of | Seoul National University Hospital ( Site 0405) | Seoul | |
| Korea, Republic of | Severance Hospital Yonsei University Health System ( Site 0402) | Seoul | |
| Mexico | Centro Estatal de Cancerologia de Chihuahua ( Site 2608) | Chihuahua | |
| Mexico | Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 2607) | Guadalajara | Jalisco |
| Mexico | Centro Oncologico Internacional. SEDNA ( Site 2609) | Mexico City | |
| Mexico | Grupo Medico Camino SC ( Site 2613) | Mexico City | |
| Mexico | Boca Raton Clinical Research QTO ( Site 2611) | Queretaro | |
| Mexico | Hospital San Lucas Cardiologica del Sureste ( Site 2606) | Tuxtla Gutierrez | Chiapas |
| Netherlands | Meander Medisch Centrum ( Site 1602) | Amersfoort | Utrecht |
| Netherlands | Antoni van Leeuwenhoek Ziekenhuis ( Site 1603) | Amsterdam | Noord-Holland |
| Netherlands | Vrije Universiteit Medisch Centrum ( Site 1601) | Amsterdam | Noord-Holland |
| Netherlands | Radboud University Medical Center ( Site 1606) | Nijmegen | Gelderland |
| Netherlands | Franciscus Gasthuis en Vlietland ( Site 1605) | Schiedam | Zuid-Holland |
| Netherlands | St. Antonius Ziekenhuis ( Site 1600) | Utrecht | |
| Netherlands | Isala Klinieken, Locatie Sophia ( Site 1604) | Zwolle | Overijssel |
| New Zealand | Auckland City Hospital ( Site 0321) | Auckland | |
| Peru | Hospital Nacional Carlos Alberto Seguin Escobedo ESSALUD ( Site 2700) | Arequipa | Ariqipa |
| Peru | Hospital Militar Central [Lima, Peru] ( Site 2704) | Lima | |
| Peru | Hospital Nacional Guillermo Almenara Irigoyen ( Site 2708) | Lima | |
| Peru | Instituto de Oncologia y Radioterapia Clinica Ricardo Palma ( Site 2706) | Lima | |
| Peru | Clinica Peruano Americana S.A. ( Site 2702) | Trujillo | La Libertad |
| Poland | Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 1716) | Bydgoszcz | Kujawsko-pomorskie |
| Poland | Szpital Uniwersytecki nr 1 im. Dr. Antoniego Jurasza w Bydgoszczy ( Site 1720) | Bydgoszcz | Kujawsko-pomorskie |
| Poland | Wojewodzki Szpital Specjalistyczny nr 4 w Bytomiu ( Site 1717) | Bytom | Slaskie |
| Poland | Szpital Wojewodzki im. Mikolaja Kopernika ( Site 1709) | Koszalin | Zachodniopomorskie |
| Poland | Szpital Uniwersytecki w Krakowie ( Site 1707) | Krakow | Malopolskie |
| Poland | Szpital Kliniczny im. Przemienienia Panskiego Uniwersytetu Medycznego im. K. Marcinkowskiego w Pozna | Poznan | Wielkopolskie |
| Poland | Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu ( Site 1700) | Przemysl | Podkarpackie |
| Poland | Radomskie Centrum Onkologii ( Site 1701) | Radom | Mazowieckie |
| Poland | Twoja Przychodnia - Szczeciskie Centrum Medyczne ( Site 1721) | Szczecin | Zachodniopomorskie |
| Poland | Nasz Lekarz Przychodnie Medyczne ( Site 1718) | Torun | Kujawsko-pomorskie |
| Russian Federation | Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 1810) | Krasnoyarsk | Krasnoyarskiy Kray |
| Russian Federation | Russian Scientific Center of Roentgenoradiology ( Site 1800) | Moscow | Moskva |
| Russian Federation | SBIH City clinical hospital named after D.D. Pletniov ( Site 1813) | Moscow | Moskva |
| Russian Federation | Volga District Medical Center Federal Medical and Biological Agency ( Site 1805) | Nizhny Novgorod | Nizhegorodskaya Oblast |
| Russian Federation | Omsk Clinical Oncology Dispensary ( Site 1809) | Omsk | Omskaya Oblast |
| Spain | Hospital Josep Trueta ( Site 1900) | Girona | Gerona |
| Spain | Instituto Catalan de Oncologia - ICO ( Site 1901) | Hospitalet de Llobregat | Barcelona |
| Spain | Hospital Universitario Lucus Augusti ( Site 1905) | Lugo | |
| Spain | Hospital 12 de Octubre de Madrid ( Site 1903) | Madrid | |
| Spain | Hospital Clinico San Carlos ( Site 1906) | Madrid | |
| Spain | Hospital Universitario Ramon y Cajal ( Site 1902) | Madrid | |
| Spain | Hospital Virgen de la Macarena ( Site 1904) | Sevilla | |
| Switzerland | Kantonsspital Graubuenden ( Site 2003) | Chur | Grisons |
| Switzerland | CHUV (centre hospitalier universitaire vaudois) ( Site 2002) | Lausanne | Vaud |
| Switzerland | Kantonsspital St. Gallen ( Site 2000) | St. Gallen | Sankt Gallen |
| Switzerland | Universitaetsspital Zuerich ( Site 2001) | Zuerich | Zurich |
| Taiwan | Kaohsiung Chang Gung Memorial Hospital ( Site 0504) | Kaohsiung | |
| Taiwan | National Cheng Kung University Hospital ( Site 0503) | Tainan | |
| Taiwan | National Taiwan University Hospital ( Site 0500) | Taipei | |
| Taiwan | Taipei Veterans General Hospital ( Site 0501) | Taipei | |
| Taiwan | Chang Gung Medical Foundation. Linkou ( Site 0502) | Taoyuan | |
| Thailand | Chulalongkorn Hospital, Medical Oncology Unit ( Site 0600) | Bangkok | Krung Thep Maha Nakhon |
| Thailand | Faculty of Medicine Siriraj Hospital ( Site 0602) | Bangkok | Krung Thep Maha Nakhon |
| Thailand | Ramathibodi Hospital. ( Site 0601) | Bangkok | Krung Thep Maha Nakhon |
| Thailand | Srinagarind Hospital ( Site 0604) | Khon Kaen | |
| Turkey | Acibadem Adana Hastanesi ( Site 2106) | Adana | |
| Turkey | Ankara Sehir Hastanesi ( Site 2103) | Ankara | |
| Turkey | Ankara Universitesi Tip Fakultesi. ( Site 2101) | Ankara | |
| Turkey | Hacettepe Universitesi Tip Fakultesi ( Site 2105) | Ankara | |
| Turkey | Istanbul Uni. Cerrahpasa Tip Fakultesi ( Site 2100) | Istanbul | |
| Turkey | Ege University Medical Faculty Tulay Aktas Oncology Hospital ( Site 2102) | Izmir | |
| Turkey | Konya Necmettin Erbakan University Medical Faculty ( Site 2104) | Konya | |
| United Kingdom | Aberdeen Royal Infirmary ( Site 1315) | Aberdeen | Aberdeen City |
| United Kingdom | Velindre Cancer Centre Hospital ( Site 1322) | Cardiff | |
| United Kingdom | Royal Marsden NHS Foundation Trust ( Site 1318) | London | London, City Of |
| United Kingdom | University College London Hospitals NHS Foundation Trust ( Site 1320) | London | London, City Of |
| United Kingdom | Royal Cornwall Hospitals NHS Trust ( Site 1317) | Truro | Cornwall |
| United States | Alaska Clinical Research Center ( Site 0274) | Anchorage | Alaska |
| United States | Providence Alaska Medical Center ( Site 0276) | Anchorage | Alaska |
| United States | Winship Cancer Institute of Emory University ( Site 0209) | Atlanta | Georgia |
| United States | University of Colorado, Anschutz Cancer Pavilion ( Site 0236) | Aurora | Colorado |
| United States | MidLantic Urology ( Site 0273) | Bala-Cynwyd | Pennsylvania |
| United States | The Sidney Kimmel Comprehensive Cancer Center ( Site 0204) | Baltimore | Maryland |
| United States | St. Vincent Frontier Cancer Center-Research ( Site 0213) | Billings | Montana |
| United States | Ralph H. Johnson VA Center ( Site 0256) | Charleston | South Carolina |
| United States | The University of Chicago ( Site 0264) | Chicago | Illinois |
| United States | Tri-State Urologic Services PSC, Inc. ( Site 0253) | Cincinnati | Ohio |
| United States | City of Hope Medical Center ( Site 0217) | Duarte | California |
| United States | Duke University ( Site 0206) | Durham | North Carolina |
| United States | Inova Health System ( Site 0205) | Fairfax | Virginia |
| United States | Comprehensive Cancer Centers of Nevada ( Site 0269) | Las Vegas | Nevada |
| United States | UCLA Hematology/Oncology - Santa Monica ( Site 0241) | Los Angeles | California |
| United States | Hartford HealthCare Medical Group ( Site 0212) | Manchester | Connecticut |
| United States | Carolina Urologic Research Center ( Site 0259) | Myrtle Beach | South Carolina |
| United States | Urology Associates [Nashville, TN] ( Site 0233) | Nashville | Tennessee |
| United States | Smilow Cancer Center at Yale-New Haven ( Site 0250) | New Haven | Connecticut |
| United States | Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0270) | New York | New York |
| United States | Weill Cornell Medical College ( Site 0263) | New York | New York |
| United States | Seattle Cancer Care Alliance ( Site 0258) | Seattle | Washington |
| United States | Springfield Clinic [Springfield, IL] ( Site 0240) | Springfield | Illinois |
| United States | Associated Medical Professionals of NY ( Site 0251) | Syracuse | New York |
| United States | Cotton-O'Neil Cancer Center ( Site 0228) | Topeka | Kansas |
| United States | Urology of Virginia ( Site 0224) | Virginia Beach | Virginia |
| United States | Sibley Memorial Hospital ( Site 0275) | Washington | District of Columbia |
| Lead Sponsor | Collaborator |
|---|---|
| Merck Sharp & Dohme LLC |
United States, Australia, Austria, Brazil, Canada, Chile, China, Colombia, Denmark, Finland, France, Germany, Ireland, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, New Zealand, Peru, Poland, Russian Federation, Spain, Switzerland, Taiwan, Thailand, Turkey, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| 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 (BICR) | rPFS was defined as the time from randomization to occurrence of: radiological tumor progression using RECIST 1.1 as assessed by BICR; progression of bone lesions using PCWG criteria; or death due to any cause. Progression as per modified RECIST 1.1 was =20% increase in sum of diameters of target lesions and progression of existing non-target lesions. Progression of bone lesions by PCWG criteria was the appearance of =2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and was persistent for =6 weeks. The rPFS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without a rPFS event were censored at the date of last disease assessment. | Up to approximately 32 months | |
| Primary | Overall Survival (OS) | OS was defined as the time from randomization to death due to any cause. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. | Up to approximately 32 months | |
| Secondary | Time to Initiation of the First Subsequent Anti-cancer Therapy or Death (TFST) | TFST was defined as the time from randomization to initiation of the first subsequent anti-cancer therapy or death; whichever occurred first. The TFST was calculated using the product limit (Kaplan-Meier) method for censored data. Participants without documented event at time of analysis will be censored at the date of last known time to have not received subsequent new anti-cancer therapy. | Up to Approximately 32 months | |
| Secondary | Time to First Symptomatic Skeletal-related Event (TTSSRE) | TTSSRE was the time from randomization to the first symptomatic skeletal-related event defined as: use of external-beam radiation therapy (EBRT) to prevent or relieve skeletal symptoms, occurrence of new symptomatic pathologic bone fracture (vertebral or nonvertebral), occurrence of spinal cord compression, or tumor-related orthopedic surgical intervention, whichever occurs first. The TTSSRE was calculated using the Kaplan-Meier method for censored data. Participants without symptomatic skeletal-related events were censored at the last evaluable assessment. | Up to Approximately 32 months | |
| Secondary | Time to Prostate-specific Antigen (PSA) Progression | Time to PSA progression was the time from randomization to PSA progression. The PSA progression date was 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. Time to PSA was calculated using Kaplan-Meier method for censored data. Participants without PSA progression were censored at the last PSA date. | Up to Approximately 32 months | |
| Secondary | Time to Radiographic Soft Tissue Progression Per Soft Tissue Rules of PCWG-Modified RECIST 1.1 as Assessed by BICR | The time to radiographic soft tissue progression was defined as the time from randomization to radiographic soft tissue progression per soft tissue rules of PCWG-modified RECIST 1.1 as assessed by BICR. Progression was defined as =20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of =5 mm. The appearance of one or more new lesions was also considered progression. Time to radiographic soft tissue progression was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without radiographic soft tissue progression were censored at the last evaluable assessment. | Up to Approximately 32 months | |
| 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 Use | TTPP was defined as the time from randomization to pain progression as determined by Item 3 of the BPI-SF. Pain progression was defined as: 1) For participants asymptomatic at baseline: a >2-point change from baseline in the average BPI-SF item 3 score at 2 consecutive visits or initiation of opioid use for pain 2) For participants symptomatic at baseline (average BPI-SF Item 3 score >0 and/or currently taking opioids; a >2-point change from baseline in the average BPI-SF Item 3 score and the average worst pain score >4 and no decrease in average opioid use. TTPP was calculated using the Kaplan-Meier method for censored data. Participants who had > 2 consecutive visits that were not evaluable for pain progression were censored at the last evaluable assessment. | Up to Approximately 32 months | |
| Secondary | 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) | PFS2 was defined as the time from randomization to disease progression as determined by investigator assessment of radiological or clinical progression after next-line of therapy or death from any cause, whichever occurs first. | Up to Approximately 32 months | |
| Secondary | Prostate-specific Antigen (PSA) Response Rate | PSA response rate was the percentage of participants who had PSA response defined as a reduction in the PSA level from baseline by >50%. The reduction in PSA level was confirmed by an additional PSA evaluation performed >3 weeks from the original response. | Up to Approximately 32 Months | |
| Secondary | Prostate-specific Antigen (PSA) Undetectable | PSA undetectable rate was defined as the percentage of participants with detectable PSA (> 0.2 ng/mL) at baseline, which becomes undetectable (< 0.2 ng/mL) during study treatment. | Up to Approximately 32 Months | |
| Secondary | Objective Response Rate (ORR) Per PCWG-Modified RECIST 1.1 as Assessed by BICR | ORR 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 base 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 Approximately 32 Months | |
| Secondary | Duration of Response (DOR) Per PCWG- Modified RECIST 1.1 as Assessed by BICR | 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 a 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. | Up to Approximately 32 Months | |
| Secondary | Number of Participants Who Experience an Adverse Event (AE) | An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could therefore have been any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Participants who experienced an AE will be reported for each arm. | Up to Approximately 59 Months | |
| Secondary | Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) | An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue study treatment due to an AE will be reported for each arm. | Up to Approximately 59 Months |
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