Study of Pembrolizumab (MK-3475) Plus Olaparib Versus Abiraterone Acetate or Enzalutamide in Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-7339-010/KEYLYNK-010)

Prostatic Neoplasms Clinical Trial

— KEYLYNK-010  

Official title:

A Phase 3, Randomized Open-label Study of Pembrolizumab (MK-3475) Plus Olaparib Versus Abiraterone Acetate or Enzalutamide in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) Who Are Unselected for Homologous Recombination Repair Defects and Have Failed Prior Treatment With One Next-generation Hormonal Agent (NHA) and Chemotherapy (KEYLYNK-010)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03834519
• Other study ID #: 7339-010
• Secondary ID: MK-7339-010KEYLY
• Status: Completed
• Phase: Phase 3
• Start date: May 2, 2019
• Est. completion date: January 27, 2024

Study information

• Verified date: January 2024
• 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 the polyadenosine 5'-diphosphoribose poly (ADP-ribose) polymerase (PARP) inhibitor olaparib and pembrolizumab in the treatment of participants with mCRPC who have failed to respond to either abiraterone acetate or enzalutamide (but not both) and to chemotherapy.

The primary study hypotheses are that the combination of pembrolizumab plus olaparib is superior to abiraterone acetate or enzalutamide with respect to:

1. Overall Survival (OS) and

2. Radiographic progression-free survival (rPFS) per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 as assessed by blinded independent central review (BICR)

As of Amendment 06, the Data Monitoring Committee (DMC) is no longer applicable. Participants still on treatment may have the option to continue receiving study intervention or SOC if they are deriving clinical benefit, until criteria for discontinuation are met. Participants who are still on study treatment and deriving clinical benefit will no longer have tumor response assessments by BICR. However, local tumor imaging assessments should continue per SOC schedule. In addition, ePRO assessments will no longer be performed and biomarker samples will no longer be collected.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 793
• Est. completion date: January 27, 2024
• Est. primary completion date: March 14, 2022
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology

• Has prostate cancer progression while receiving androgen deprivation therapy (or post bilateral orchiectomy) within 6 months before screening

• Has current evidence of metastatic disease documented by bone lesions on bone scan and/or soft tissue disease shown by computed tomography/magnetic resonance imaging (CT/MRI)

• Has received prior treatment with abiraterone acetate OR enzalutamide, but not both

• Have disease that progressed during or after treatment with abiraterone acetate for either metastatic hormone-sensitive prostate cancer (mHSPC) or mCRP or enzalutamide for mCRPC for at least 8 weeks (at least 14 weeks for participants with bone progression)

• Participants that received abiraterone acetate for mHSPC may not have received abiraterone acetate or enzalutamide for mCRPC

• Have received docetaxel chemotherapy regimen for mCRPC and have had progressive disease during or after treatment with docetaxel

• Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<2.0 nM)

• If receiving bone resorptive therapy, including but not limited to bisphosphonates or denosumab, must have been receiving stable doses before randomization

• Must agree to refrain from donating sperm during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention PLUS be abstinent from heterosexual intercourse OR must agree to use contraception unless confirmed to be azoospermic

• Contraception use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirement above, the local label requirements are to be followed.

• Has provided tumor tissue from a fresh core or excisional biopsy (obtained within 12 months of screening) from soft tissue not previously irradiated. Samples from tumors progressing at 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 the past 2 years

• Has a history of (noninfectious) pneumonitis requiring steroids, or has current pneumonitis

• Has known active human immunodeficiency virus (HIV), hepatitis B virus (e.g., hepatitis B surface antigen reactive) or hepatitis C virus (HCV) infection (e.g., HCV RNA [qualitative] is detected)

• Has known active 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 myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or has features suggestive of MDS/AML

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy

• Has (=Grade 3) hypersensitivity to pembrolizumab and/or any of its excipients

• Has known hypersensitivity to the components or excipients in olaparib, abiraterone acetate, prednisone or prednisolone, or enzalutamide

• Has symptomatic congestive heart failure (New York Heart Association Class III or IV heart disease)

• Has received an anticancer monoclonal antibody (mAb) before randomization

• Has received prior treatment with olaparib or any other PARP inhibitor

• Has received prior treatment with apalutamide or darolutamide

• Has received prior treatment with enzalutamide or apalutamide for metastatic hormone-sensitive prostate cancer

• Has used herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA (e.g., saw palmetto) before the date of randomization

• Has received prior treatment with radium or other therapeutic radiopharmaceuticals for prostate cancer

• Has received prior treatment with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent, or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, or CD137)

• Is currently receiving either strong or moderate inhibitors of cytochrome P450 [CYP] (CYP3A4) that cannot be discontinued for the duration of the study

• Has received a previous allogenic bone marrow transplant or double umbilical cord transplantation (dUCBT) or a solid organ transplant

• Has received a live vaccine within 30 days prior to the date of randomization

• Is currently participating in or has participated in a study of an investigational agent, or has used an investigational device, within 4 weeks before the date of randomization

• Has a bone "superscan"

• Is expecting to father children within the projected duration of the study, starting with the screening visit through 90 days after the last dose of study intervention

Related Conditions & MeSH terms

• Prostatic Neoplasms

Intervention

Biological:
• Pembrolizumab
IV infusion

Drug:
• Olaparib
Oral tablets
• Abiraterone acetate
Oral tablets
• Prednisone
Oral tablets
• Enzalutamide
Oral tablets or oral capsules
• Prednisolone
Oral tablets

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	Hospital Aleman ( Site 1004)	Buenos Aires
Argentina	Hospital Britanico de Buenos Aires ( Site 1006)	Buenos Aires	Caba
Argentina	Instituto de Investigaciones Metabolicas ( Site 1011)	Buenos Aires
Argentina	Instituto Medico Alexander Fleming ( Site 1010)	Buenos Aires
Argentina	CEMAIC ( Site 1014)	Cordoba
Argentina	Sanatorio Parque ( Site 1002)	Rosario	Santa Fe
Australia	Box Hill Hospital ( Site 0146)	Box Hill	Victoria
Australia	St. Vincent's Hospital ( Site 0158)	Darlinghurst	New South Wales
Australia	Royal Brisbane and Women s Hospital ( Site 0155)	Herston	Queensland
Australia	Macquarie University ( Site 0151)	Macquarie University	New South Wales
Australia	Peter MacCallum Cancer Centre ( Site 0152)	Melbourne	Victoria
Australia	Fiona Stanley Hospital ( Site 0162)	Murdoch	Western Australia
Australia	Port Macquarie Base Hospital ( Site 0153)	Port Macquarie	New South Wales
Australia	John Flynn Hospital & Medical Centre ( Site 0164)	Tugun	Queensland
Australia	Calvary Mater Newcastle ( Site 0148)	Waratah	New South Wales
Australia	Southern Medical Day Care Centre ( Site 0160)	Wollongong	New South Wales
Austria	Medizinische Universitat Graz ( Site 0374)	Graz	Steiermark
Austria	Ordensklinikum Linz GmbH Elisabethinen ( Site 0373)	Linz	Oberosterreich
Austria	SCRI-CCCIT GesmbH ( Site 0371)	Salzburg
Austria	Medizinische Universitaet Wien ( Site 0375)	Wien
Brazil	Hospital de Caridade de Ijui ( Site 1038)	Ijui	Rio Grande Do Sul
Brazil	Centro de Novos Tratamentos Itajai - Clinica de Neoplasias Litoral ( Site 1035)	Itajai	Santa Catarina
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	IBCC - Instituto Brasileiro de Controle do Câncer ( Site 1040)	São Paulo	Sao Paulo
Canada	William Osler Health System (Brampton Civic Hospital) ( Site 0121)	Brampton	Ontario
Canada	Cross Cancer Institute ( Site 0110)	Edmonton	Alberta
Canada	Nova Scotia Health Authority QEII-HSC ( Site 0114)	Halifax	Nova Scotia
Canada	Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0116)	Hamilton	Ontario
Canada	BC Cancer-Kelowna - Sindi Ahluwalia Hawkins Centre ( Site 0113)	Kelowna	British Columbia
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	Princess Margaret Cancer Centre ( Site 0107)	Toronto	Ontario
Canada	BC Cancer-Vancouver Center ( Site 0112)	Vancouver	British Columbia
Chile	Bradford Hill Centro de Investigaciones Clinicas ( 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
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	Centre Leon Berard ( Site 0422)	Lyon	Rhone
France	Institut Paoli Calmettes ( Site 0419)	Marseille	Bouches-du-Rhone
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	Institut Gustave Roussy ( Site 0416)	Villejuif	Val-de-Marne
Germany	Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0301)	Berlin
Germany	Universitaetsklinikum Duesseldorf ( Site 0306)	Duesseldorf	Nordrhein-Westfalen
Germany	Universitaetsklinikum Erlangen ( Site 0303)	Erlangen	Bayern
Germany	Universitaetsklinikum Freiburg - Medizinische Klinik ( Site 0304)	Freiburg	Baden-Wurttemberg
Germany	Universitaetsklinikum Jena ( Site 0305)	Jena	Thuringen
Germany	Universitaetsklinikum in Mannheim ( Site 0314)	Mannheim	Baden-Wurttemberg
Germany	Klinikum Rechts der Isar ( Site 0300)	Muenchen	Bayern
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
Ireland	Tallaght University Hospital ( Site 0730)	Dublin
Ireland	Mid Western Cancer Centre ( Site 0728)	Limerick
Israel	Ha Emek Medical Center ( Site 0548)	Afula
Israel	Assaf Harofe ( Site 0547)	Be'er- Ya'akov
Israel	Soroka Medical Center ( Site 0549)	Beer Sheva
Israel	Rambam Medical Center ( 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
Italy	Medical Oncology Ospedale San Donato ( Site 0461)	Arezzo
Italy	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 ( Site 0462)	Meldola	Emilia-Romagna
Italy	Azienda Ospedaliera San Camillo Forlanini ( Site 0455)	Roma
Italy	Fondazione Policlinico Universitario A. Gemelli ( Site 0463)	Roma
Italy	Istituto Clinico Humanitas Research Hospital ( Site 0452)	Rozzano	Lombardia
Italy	Azienda Ospedaliera Santa Maria Terni ( Site 0456)	Terni
Italy	Presidio Ospedaliero Santa Chiara ( Site 0451)	Trento
Japan	Chiba Cancer Center ( Site 0704)	Chiba
Japan	Fuji City General Hospital ( Site 0725)	Fuji	Shizuoka
Japan	Kyushu University Hospital ( Site 0718)	Fukuoka
Japan	Hamamatsu University Hospital ( Site 0720)	Hamamatsu	Shizuoka
Japan	Saitama Medical University International Medical Center ( Site 0708)	Hidaka	Saitama
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	Kobe City Medical Center General Hospital ( Site 0726)	Kobe	Hyogo
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	Nagano Municipal Hospital ( Site 0723)	Nagano
Japan	Nagasaki University Hospital ( Site 0719)	Nagasaki
Japan	Osaka International Cancer Institute ( Site 0722)	Osaka
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	Fujita Health University Hospital ( Site 0724)	Toyoake	Aichi
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 0176)	Goyang-si	Kyonggi-do
Korea, Republic of	Chonnam National University Hwasun Hospital ( Site 0174)	Hwasun Gun	Jeonranamdo
Korea, Republic of	Samsung Medical Center ( Site 0172)	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System ( Site 0173)	Seoul
Korea, Republic of	Asan Medical Center ( Site 0171)	Songpagu	Seoul
Netherlands	Antoni van Leeuwenhoek Ziekenhuis ( Site 0480)	Amsterdam	Noord-Holland
Netherlands	Vrije Universiteit Medisch Centrum ( Site 0479)	Amsterdam	Noord-Holland
Netherlands	Ziekenhuisgroep Twente ( Site 0469)	Hengelo	Overijssel
Netherlands	Spaarne Ziekenhuis ( Site 0473)	Hoofddorp	Noord-Holland
Netherlands	Medisch Centrum Leeuwarden ( Site 0477)	Leeuwarden	Fryslan
Netherlands	Haaglanden MC - locatie Antoniushove ( Site 0471)	Leidschendam	Zuid-Holland
Netherlands	Radboud University Medical Center ( Site 0470)	Nijmegen	Gelderland
Netherlands	Erasmus MC ( Site 0475)	Rotterdam	Zuid-Holland
Netherlands	Franciscus Gasthuis en Vlietland ( Site 0489)	Schiedam	Zuid-Holland
New Zealand	Auckland City Hospital ( Site 0193)	Auckland
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 Clinic ( Site 0323)	Barcelona
Spain	Hospital del Mar ( Site 0333)	Barcelona
Spain	Hospital General Universitari Vall d Hebron ( Site 0334)	Barcelona
Spain	Hospital San Pedro de Alcantara ( Site 0326)	Caceres	Extremadura
Spain	Hospital Josep Trueta ( Site 0321)	Girona	Gerona
Spain	Instituto Catalan de Oncologia - ICO ( Site 0330)	L Hospitalet De Llobregat	Barcelona
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
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
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	Mount Vernon Cancer Centre ( Site 0536)	Northwood
United Kingdom	University of North Midlands NHS Foundation Trust ( Site 0527)	Stoke-on-Trent	Staffordshire
United Kingdom	Royal Marsden Hospital ( Site 0526)	Sutton	England
United Kingdom	Musgrove Park Hospital ( Site 0537)	Taunton	England
United Kingdom	Torbay Hospital ( Site 0532)	Torquay	Devon
United States	University of New Mexico Cancer Center ( Site 0048)	Albuquerque	New Mexico
United States	Georgia Cancer Center at Augusta University ( Site 0026)	Augusta	Georgia
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 0005)	Baltimore	Maryland
United States	St. Vincent Frontier Cancer Center ( Site 0016)	Billings	Montana
United States	Beth Israel Deaconess Medical Ctr. ( Site 0093)	Boston	Massachusetts
United States	Dana Farber Cancer Institute ( Site 0033)	Boston	Massachusetts
United States	Gabrail Cancer Center-Research ( Site 0097)	Canton	Ohio
United States	Duke Cancer Center Cary ( Site 0010)	Cary	North Carolina
United States	The Urology Group- Cincinnati ( Site 0094)	Cincinnati	Ohio
United States	University Hospitals of Cleveland Seidman Cancer Center ( Site 0036)	Cleveland	Ohio
United States	Barbara Ann Karmanos Cancer Institute ( Site 0077)	Detroit	Michigan
United States	Henry Ford Health System ( Site 0039)	Detroit	Michigan
United States	St. Joseph Heritage Healthcare ( Site 0069)	Fullerton	California
United States	Memorial Medical Center ( Site 0095)	Las Cruces	New Mexico
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	Froedtert and Medical College of Wisconsin ( Site 0045)	Milwaukee	Wisconsin
United States	Carolina Urologic Research Center ( Site 0070)	Myrtle Beach	South Carolina
United States	Tulane Cancer Center ( Site 0066)	New Orleans	Louisiana
United States	Nebraska Cancer Specialists ( Site 0034)	Omaha	Nebraska
United States	Quincy Medical Group ( Site 0021)	Quincy	Illinois
United States	Virginia Cancer Institute ( Site 0052)	Richmond	Virginia
United States	Blue Ridge Cancer Care ( Site 0086)	Roanoke	Virginia
United States	Huntsman Cancer Institute ( Site 0002)	Salt Lake City	Utah
United States	Seattle Cancer Care Alliance ( Site 0079)	Seattle	Washington
United States	Associated Medical Professionals of NY ( Site 0060)	Syracuse	New York
United States	Chesapeake Urology Research Associates ( Site 0076)	Towson	Maryland
United States	Sibley Memorial Hospital ( Site 0096)	Washington	District of Columbia
United States	UMass Memorial Medical Center ( 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,  Canada,  Chile,  France,  Germany,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  New Zealand,  Russian Federation,  Spain,  Taiwan,  United Kingdom, 

References & Publications (1)

Antonarakis ES, Park SH, Goh JC, Shin SJ, Lee JL, Mehra N, McDermott R, Sala-Gonzalez N, Fong PC, Greil R, Retz M, Sade JP, Yanez P, Huang YH, Begbie SD, Gafanov RA, De Santis M, Rosenbaum E, Kolinsky MP, Rey F, Chiu KY, Roubaud G, Kramer G, Sumitomo M, M — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	Overall survival (OS) is defined as the time from randomization to death due to any cause. The nonparametric Kaplan-Meier method was used to estimate the survival curves.	Up to ~31 months
Primary	Radiographic Progression-Free Survival (rPFS)	rPFS is defined as the time from randomization to the first documented progressive disease (PD) per PCWG-modified RECIST 1.1 based on BICR or death due to any cause, whichever occurred first. Per PCWG-modified RECIST 1.1, PD is 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 or =2 new bone lesions was also considered PD. PCWG-modified RECIST is similar to RECIST 1.1 with the exception that a confirmation assessment of PD (>4 weeks after the initial PD) is required for participants who remain on treatment following a documented PD per RECIST 1.1 and PCWG rules include new bone lesions. The rPFS per PCWG-modified RECIST as assessed by BICR for all participants is presented. The nonparametric Kaplan-Meier method was used to estimate the survival curves.	Up to ~31 months
Secondary	Time to Initiation of the First Subsequent Anticancer Therapy (TFST)	TFST is the time from randomization to initiation of the first subsequent anticancer therapy defined as the first anti-cancer treatment not part of the study arm for a given participant, or death, whichever occurs first. The nonparametric Kaplan-Meier method was used to estimate the survival curves.	Up to ~31 months
Secondary	Objective Response Rate (ORR)	ORR is 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) bone scan) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions per RECIST 1.1 and Non-PD, non-evaluable (NE), or NED bone scan or CR with non-PD or NE bone scan.) The percentage of participants who experienced CR or PR as assessed by BICR is presented.	Up to ~31 months
Secondary	Duration of Response (DOR)	DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per PCWG-modified RECIST 1.1, PD is 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. The appearance of = 2 new bone lesions is also considered PD. DOR as assessed by BICR is presented.	Up to ~24 months
Secondary	Time to Prostate-Specific Antigen (PSA) Progression	Time to PSA progression is defined as the 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. The nonparametric Kaplan-Meier method was used to estimate the survival curves.	Up to ~31 months
Secondary	Time to First Symptomatic Skeletal-Related Event (SSRE)	SSRE is defined as the time from randomization to the first symptomatic skeletal-related event, defined as whichever occurs first: First 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	Up to ~31 months
Secondary	Time to Radiographic Soft Tissue Progression	Time to radiographic soft tissue progression is defined as the time from randomization to radiographic soft tissue progression per soft tissue rule of PCWG-modified RECIST 1.1. Progression is 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. The appearance of one or more new lesions is also considered progression. Time to radiographic soft tissue progression as assessed by BICR is presented.	Up to ~31 months
Secondary	Time to Pain Progression (TTPP)	TTPP is defined as the time from randomization to pain progression as determined by Item 3 of the Brief Pain Inventory Short Form (BPI-SF) and by the Analgesic Quantification Algorithm (AQA) score.; Pain progression is defined as: For participants who are asymptomatic at baseline, a =2-point change from baseline in the average (4-7 days) BPI-SF item 3 score at 2 consecutive visits OR initiation of opioid use for pain; For participants who are 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 an average worst pain score =4 and no decrease in average opioid use (=1-point decrease in AQA score from a starting value of 2 or higher) OR any increase in opioid use at 2 consecutive follow-up visits.; Participants who had more than 2 consecutive visits that were not evaluable for pain progression were censored at the last evaluable assessment.	Up to ~31 months
Secondary	Number of Participants Who Experience an Adverse Event (AE)	An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experienced an adverse event are presented.	Up to ~31 months
Secondary	Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)	The number of participants who discontinue study treatment due to an AE are presented.	Up to ~880 Days

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