A Study of Apalutamide in Participants With High-Risk, Localized or Locally Advanced Prostate Cancer Who Are Candidates for Radical Prostatectomy

NCT ID: NCT03767244

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

2517 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-06-11

Study Completion Date

2028-10-13

Brief Summary

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The purpose of this study is to determine if treatment with apalutamide plus androgen deprivation therapy (ADT) before and after radical prostatectomy (RP) with pelvic lymph node dissection (pLND) in participants with high-risk localized or locally advanced prostate cancer results in an improvement in pathological complete response (pCR) rate and metastasis-free survival (MFS) as compared to placebo plus ADT.

Detailed Description

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Conditions

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Prostatic Neoplasms

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo + ADT

Participants will receive ADT with oral administration of matching placebo treatment daily in each cycle (each cycle of 28 days). Participants will receive six cycles of placebo treatment, followed by RP with pLND, followed by an additional six cycles of placebo treatment. A LTE may be initiated at sponsor's discretion after completion of the primary endpoint analysis.

Group Type EXPERIMENTAL

Androgen Deprivation Therapy (ADT)

Intervention Type DRUG

Participants will receive a stable regimen of ADT - gonadotropin-releasing hormone analog (agonist or antagonist) (GnRHa). ADT is a kind of hormone therapy for prostate cancer. GnRHa will be administrated to achieve and maintain sub-castrate concentrations of testosterone (50 nanogram per deciliter \[ng/dL\]).

Placebo

Intervention Type DRUG

Participants will receive matching placebo oral tablets daily.

Apalutamide + ADT

Participants will receive androgen deprivation therapy (ADT) plus oral administration of apalutamide 240 milligram (mg) (4 tablets of 60 mg each) daily in each cycle (each cycle of 28 days). Participants will receive six cycles of treatment, followed by radical prostatectomy (RP) with pelvic lymph node dissection (pLND), followed by an additional six cycles of treatment. A Long-Term Extension (LTE) may be initiated at sponsor's discretion after completion of the primary endpoint analysis.

Group Type EXPERIMENTAL

Apalutamide

Intervention Type DRUG

Participants will receive apalutamide 240 mg (4 tablets of 60 mg each) orally once daily.

Androgen Deprivation Therapy (ADT)

Intervention Type DRUG

Participants will receive a stable regimen of ADT - gonadotropin-releasing hormone analog (agonist or antagonist) (GnRHa). ADT is a kind of hormone therapy for prostate cancer. GnRHa will be administrated to achieve and maintain sub-castrate concentrations of testosterone (50 nanogram per deciliter \[ng/dL\]).

Interventions

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Apalutamide

Participants will receive apalutamide 240 mg (4 tablets of 60 mg each) orally once daily.

Intervention Type DRUG

Androgen Deprivation Therapy (ADT)

Participants will receive a stable regimen of ADT - gonadotropin-releasing hormone analog (agonist or antagonist) (GnRHa). ADT is a kind of hormone therapy for prostate cancer. GnRHa will be administrated to achieve and maintain sub-castrate concentrations of testosterone (50 nanogram per deciliter \[ng/dL\]).

Intervention Type DRUG

Placebo

Participants will receive matching placebo oral tablets daily.

Intervention Type DRUG

Other Intervention Names

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JNJ-56021927

Eligibility Criteria

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Inclusion Criteria

* Histologically confirmed adenocarcinoma of the prostate
* High-risk disease defined by a total Gleason Sum Score greater than equal to (\>=) 4+3 (=Grade Groups \[GG\] 3-5) and \>=1 of the following 4 criteria: a) Any combination of Gleason Score 4+3 (= 3) and Gleason Score 8 (4+4 or 5+3) in \>= 6 systematic cores (with \>=1 core Gleason Score 8 \[4+4 or 5+3\] included); b) Any combination of Gleason Score 4+3 (=GG 3) and Gleason Score 8 (4+4 or 5+3) in \>=3 systematic cores and Prostate-specific antigen (PSA) \>=20 ng/mL (with \>= 1 core Gleason Score 8 \[4+4 or 5+3\] included); c) Gleason Score \>=9 (=GG 5) in at least 1 systematic or targeted core; d) At least 2 systematic or targeted cores with continuous Gleason Score \>=8 (=GG 4), each with \> 80 percent (%) involvement
* Candidate for radical prostatectomy with pelvic lymph node dissection as per the investigator
* Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
* Contraceptive use by male participants (and female partners of male participants enrolled in the study who are of childbearing potential or are pregnant) should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies
* Able to receive androgen deprivation therapy (ADT) for at least 13 months

Exclusion Criteria

* Distant metastasis based on conventional imaging (clinical stage M1). Nodal disease below the iliac bifurcation (clinical stage N1) is not an exclusion. Diagnosis of distant metastasis (clinical M stage; M0 versus M1a, M1b, M1c) and pelvic nodal disease (clinical N stage; N1 versus N0) will be assessed by central radiological review. Participants are considered eligible only if the central radiological review confirms clinical stage M0
* (a) Prior treatment with androgen receptor antagonists; (b) Treatment with gonadotropin-releasing hormone analog (GnRHa) prior to informed consent form (ICF) signature
* History of prior systemic or local therapy for prostate cancer, including pelvic radiation for prostate cancer
* Use of any investigational agent less than or equals to (\<=)4 weeks prior to randomization or any therapeutic procedure for prostate cancer at any time
* Major surgery \<=4 weeks prior to randomization
* Any of the following within 12 months prior to first dose of study drug: severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (example, pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias or New York Heart Association Class II to IV heart disease; uncomplicated deep vein thrombosis is not considered exclusionary
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Janssen Research & Development, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

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UC San Diego Moores Cancer Center

La Jolla, California, United States

Site Status

University of Southern California

Los Angeles, California, United States

Site Status

Cedars Sinai Medical Center

Los Angeles, California, United States

Site Status

University of California Los Angeles

Los Angeles, California, United States

Site Status

University of California Irvine Medical Center Chao Family Comprehensive Cancer Center

Orange, California, United States

Site Status

UC Davis Medical Center

Sacramento, California, United States

Site Status

AdventHealth Medical Group Urology of Denver

Denver, Colorado, United States

Site Status

Colorado Clinical Research

Lakewood, Colorado, United States

Site Status

Stamford Hospital

Stamford, Connecticut, United States

Site Status

Urology Specialists LLC

Hialeah, Florida, United States

Site Status

Mayo Clinic - Division Of Hematology/oncology

Jacksonville, Florida, United States

Site Status

Miami Cancer Institute at Baptist Health / Baptist Health Medical Group

Miami, Florida, United States

Site Status

Florida Hospital

Orlando, Florida, United States

Site Status

Emory University Winship Cancer Institute

Atlanta, Georgia, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Ochsner LSU Health Shreveport - Regional Urology

Shreveport, Louisiana, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Beth Isreal Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Michigan Institute of Urology, PC

Troy, Michigan, United States

Site Status

Saint Louis University

St Louis, Missouri, United States

Site Status

Urology Cancer Center, PC

Omaha, Nebraska, United States

Site Status

Albany Medical College

Albany, New York, United States

Site Status

Great Lakes Physician PC d/b/a Western New York Urology Associates

Cheektowaga, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

Weill Cornell Medical College

New York, New York, United States

Site Status

SUNY Upstate Medical University

Syracuse, New York, United States

Site Status

University of North Carolina

Chapel Hill, North Carolina, United States

Site Status

Duke University School of Medicine

Durham, North Carolina, United States

Site Status

Medication Management LLC

Greensboro, North Carolina, United States

Site Status

Carolina Urology Partners, PLLC

Huntersville, North Carolina, United States

Site Status

Cleveland VA Medical Center

Cleveland, Ohio, United States

Site Status

Oklahoma City VAMC

Oklahoma City, Oklahoma, United States

Site Status

MidLantic Urology

Bala-Cynwyd, Pennsylvania, United States

Site Status

Omega Medical Research

Warwick, Rhode Island, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Ralph H. Johnson Veterans Affairs Medical Center

Charleston, South Carolina, United States

Site Status

Greenville Health

Greenville, South Carolina, United States

Site Status

Carolina Urologic Research Center

Myrtle Beach, South Carolina, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

VA North Texas Health Care System

Dallas, Texas, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Virginia Urology

Richmond, Virginia, United States

Site Status

Urology of Virginia, PLCC

Virginia Beach, Virginia, United States

Site Status

CAMC Memorial Hospital, Charleston Area Medical Center Physicians

Charleston, West Virginia, United States

Site Status

Hospital Aleman

Caba, , Argentina

Site Status

Hospital Italiano de Buenos Aires

Ciudad Autonoma de, , Argentina

Site Status

Cemaic Centro Privado de Especialidades Medicas Ambulatorias e Investigacion Clinica

Córdoba, , Argentina

Site Status

Centro Urologico Profesor Bengio

Córdoba, , Argentina

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Uroclinica

Mendoza, , Argentina

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Clinica Mayo de UMCB

San Miguel de Tucumán, , Argentina

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Epworth Eastern Hospital

Box Hill, , Australia

Site Status

St Vincent s Hospital Sydney

Darlinghurst, , Australia

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Austin Health

Heidelberg, , Australia

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Australian Urology Associates Pty Ltd

Malvern, , Australia

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Royal Melbourne Hospital

Parkville, , Australia

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Northern Cancer Institute

St Leonards, , Australia

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Sydney Adventist Hospital

Wahroonga, , Australia

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Westmead Hospital

Westmead, , Australia

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Princess Alexandra Hospital

Woolloongabba, , Australia

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Associacao de Combate ao Cancer em Goias - Hospital de Cancer Araujo Jorge

Goiânia, , Brazil

Site Status

Oncosite - Centro de Pesquisa Clínica em Oncologia Ltda

Ijuí, , Brazil

Site Status

Liga Norte Riograndense Contra O Cancer

Natal, , Brazil

Site Status

Irmandade Santa Casa de Misericordia de Porto Alegre

Porto Alegre, , Brazil

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Universidade do Estado do Rio de Janeiro - UERJ

Rio de Janeiro, , Brazil

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Associacao Umane

São Paulo, , Brazil

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Fundacao Faculdade de Medicina - Instituto do Cancer do Estado de Sao Paulo

São Paulo, , Brazil

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Instituto Do Cancer Brasil

Três Lagoas, , Brazil

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Prostate Cancer Centre

Calgary, Alberta, Canada

Site Status

Vancouver Prostate Centre, Gordon and Leslie Diamond Health Care Centre

Vancouver, British Columbia, Canada

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Nova Scotia Health Authority

Halifax, Nova Scotia, Canada

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London Health Sciences Center

London, Ontario, Canada

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Sunnybrook Health Sciences Center

Toronto, Ontario, Canada

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Princess Margaret Cancer Centre University Health Network

Toronto, Ontario, Canada

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CHUM - Centre hospitalier universitaire de Montreal

Montreal, Quebec, Canada

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CHU de Quebec Universite Laval Hopital de l Enfant Jesus

Québec, Quebec, Canada

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Fakultni nemocnice Hradec Kralove

Hradec Králove, , Czechia

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Krajská nemocnice Liberec

Liberec, , Czechia

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Uromedical Center s.r.o.

Olomouc, , Czechia

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Fakultni nemocnice Plzen, Urologicka klinika

Pilsen, , Czechia

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Vseobecna fakultni nemocnice v Praze

Prague, , Czechia

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Thomayerova nemocnice

Prague, , Czechia

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CHU d'Angers

Angers, , France

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CHRU Besancon Hopital Jean Minjoz

Besançon, , France

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Hopital Pellegrin CHU Bordeaux

Bordeaux, , France

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APHP - Hopital Henri Mondor

Créteil, , France

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Hopital Edouard Herriot - CHU Lyon

Lyon, , France

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CHU de Nantes hotel Dieu

Nantes, , France

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Institut Mutualiste Montsouris

Paris, , France

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Clinique de la Croix du Sud

Quint-Fonsegrives, , France

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Chu Rennes Hopital Pontchaillou

Rennes, , France

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CHU de Toulouse - Hôpital Rangueil

Toulouse, , France

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CHRU Tours Hopital Bretonneau

Tours, , France

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Universitaetsklinikum der RWTH Aachen

Aachen, , Germany

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Städtisches Klinikum Braunschweig gGmbH - Standort Salzdahlumer

Braunschweig, , Germany

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Universitaetsklinikum Koelnt

Cologne, , Germany

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Praxis Dr. med. Ralf Eckert

Eisleben Lutherstadt, , Germany

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Universitatsklinikum Essen

Essen, , Germany

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Universitatsklinikum Frankfurt

Frankfurt am Main, , Germany

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Prostata zentrum Nordwest

Gronau, , Germany

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Martini-Klinik am Universitätsklinikum Hamburg-Eppendorf Urologie

Hamburg, , Germany

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Universitätsklinikum des Saarlandes

Homburg/Saar, , Germany

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Universitatsklinikum Schleswig Holstein Campus Lubeck

Lübeck, , Germany

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Klinikum St. Elisabeth Straubing GmbH

Straubing, , Germany

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Kliniken Nordoberpfalz, Klinik für Urologie

Weiden/Opf, , Germany

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Praxisgemeinschaft f. Onkologie u. Urologie - Germany

Wilhelmshaven, , Germany

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Asaf Harofe Medical Center

Beer Yaakov, , Israel

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Rambam Health Care Campus

Haifa, , Israel

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Tel Aviv University Sackler School of Medicine - Meir Medical Center (MMC)

Kfar Saba, , Israel

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Rabin Medical Center

Petah Tikva, , Israel

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The Chaim Sheba Medical Center

Ramat Gan, , Israel

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Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

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Policlinico Abano Terme

Abano Terme, , Italy

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Generale Regionale F. Miulli

Acquaviva delle Fonti, , Italy

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Ospedale di Bassano del Grappa

Bassano del Grappa, , Italy

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ASST Spedali Civili Brescia

Brescia, , Italy

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ASL2 Lanciano - Vasto - Chieti - Ospedale 'SS Annunziata' di Chieti

Chieti, , Italy

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Azienda Ospedaliero Universitaria Careggi

Florence, , Italy

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San Raffaele Turro - Istituto di Ricovero e Cura a Carattere Scientifico

Milan, , Italy

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Ospedale San Raffaele

Milan, , Italy

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Istituto Europeo di Oncologia

Milan, , Italy

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Clinica di Urologia Policlinico di Modena - Universita di Modena e reggio Emilia

Modena, , Italy

Site Status

Università del Piemonte Orientale - Ospedale Maggiore della Carità di Novara

Novara, , Italy

Site Status

Universita degli Studi di Torino - Azienda Ospedaliero-Universitaria San Luigi Gonzaga

Orbassano, , Italy

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Universita Campus Bio-Medico di Roma

Roma, , Italy

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Istituto Nazionale Tumori Regina Elena

Roma, , Italy

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Azienda Ospedaliera Sant Andrea

Roma, , Italy

Site Status

Ospedale Molinette, AO Città della Salute e della Scienza di

Torino, , Italy

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UOC di Urologia AOU Integrata di Verona - Polo Chirurgico Confortini - Ospedale Borgo Trento

Verona, , Italy

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Akita University Hospital

Akita, , Japan

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Chiba University Hospital

Chiba, , Japan

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Chiba Cancer Center

Chūōku, , Japan

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Hakodate Goryoukaku Hospital

Hakodate, , Japan

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Hirosaki University Hospital

Hirosaki, , Japan

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Kanazawa University Hospital

Kanazawa, , Japan

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Kobe City Medical Center General Hospital

Kobe, , Japan

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Dokkyo Medical University Saitama Medical Center

Koshigaya, , Japan

Site Status

Kurume University Hospital

Kurume, , Japan

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Kyoto University Hospital

Kyoto, , Japan

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National Hospital Organization Shikoku Cancer Center

Matsuyama, , Japan

Site Status

Kitasato University Hospital

Minamiku, , Japan

Site Status

University of Miyazaki Hospital

Miyazaki, , Japan

Site Status

Nagano Municipal Hospital

Nagano, , Japan

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Osaka International Cancer Institute

Osaka, , Japan

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Kindai University Hospital

Osaka Sayama Shi, , Japan

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Toho University Sakura Medical Center

Sakura, , Japan

Site Status

Hokkaido University Hospital

Sapporo, , Japan

Site Status

Iwate Medical University Hospital

Shiwa-gun, , Japan

Site Status

Nippon Medical School Hospital

Tokyo, , Japan

Site Status

Juntendo University Hospital

Tokyo, , Japan

Site Status

Yamaguchi University Hospital

Ube, , Japan

Site Status

Yokohama City University Medical Center

Yokohama, , Japan

Site Status

Antoni van Leeuwenhoek

Amsterdam, , Netherlands

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Catharinaziekenhuis

Eindhoven, , Netherlands

Site Status

St. Antonius Ziekenhuis (St. Antonius Hospital)

Nieuwegein, , Netherlands

Site Status

Canisius-Wilhelmina Ziekenhuis

Nijmegen, , Netherlands

Site Status

Samodzielny Publiczny Wielospecjalistyczny Zaklad Opieki Zdrowotnej Mswia W Bydgoszczy

Bydgoszcz, , Poland

Site Status

Szpital Uniwersytecki NR 1 IM Dr Antoniego Jurasza

Bydgoszcz, , Poland

Site Status

Szpital Wojewodzki im Mikolaja Kopernika w Koszalinie

Koszalin, , Poland

Site Status

Pratia MCM Krakow

Krakow, , Poland

Site Status

City Clinic Sp. z o.o.

Warsaw, , Poland

Site Status

Dolnoslaskie Centrum Onkologii, Oddzial Chirurgii Onkologicznej II - Urologia

Wroclaw, , Poland

Site Status

Altai Regional Oncology Dispensary

Barnaul, , Russia

Site Status

Chelyabinsk Regional Clinical Center Of Oncology And Nuclear Medicine

Chelyabinsk, , Russia

Site Status

Moscow City Clinical Hospital # 62

Moscow, , Russia

Site Status

Hertzen Oncology Research Institute

Moscow, , Russia

Site Status

Clinical Oncology Dispensary

Omsk, , Russia

Site Status

Medical-sanitary unit 'Neftyanik'

Tyumen, , Russia

Site Status

Vologda Regional Oncological Dispensary

Vologda, , Russia

Site Status

Chonnam National University Hospital

Gwangju, , South Korea

Site Status

Seoul National University Bundang Hospital

Gyeonggi-do, , South Korea

Site Status

Severance Hospital Yonsei University Health System

Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

The Catholic University of Korea Seoul St Marys Hospital

Seoul, , South Korea

Site Status

Hosp Univ A Coruna

A Coruña, , Spain

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Hosp Univ Vall D Hebron

Barcelona, , Spain

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Hosp. Puerta Del Mar

Cadiz, , Spain

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Hosp. Gral. Univ. de Castellon

Castellon, , Spain

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Hosp. de Jerez de La Frontera

Jerez de la Frontera, , Spain

Site Status

Hosp. Univ. Ramon Y Cajal

Madrid, , Spain

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Hosp. Univ. 12 de Octubre

Madrid, , Spain

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Hosp. Univ. La Paz

Madrid, , Spain

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Fund. Hosp. de Manacor

Manacor, , Spain

Site Status

Hosp Virgen de La Victoria

Málaga, , Spain

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Hosp. Univ. Marques de Valdecilla

Santander, , Spain

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Hosp. Virgen Del Rocio

Seville, , Spain

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Inst. Valenciano de Oncologia

Valencia, , Spain

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Hosp. Clinico Univ. de Valencia

Valencia, , Spain

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Kaohsiung Medical University Chung Ho Memorial Hospital

Kaohsiung City, , Taiwan

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China Medical University Hospital

Taichung, , Taiwan

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Taichung Veterans General Hospital

Taichung, , Taiwan

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Tungs' Taichung MetroHarbor Hospital

Taichung, , Taiwan

Site Status

Chi Mei Medical Center Yong Kang

Tainan, , Taiwan

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National Taiwan University Hospital.

Taipei, , Taiwan

Site Status

Southmead Hospital

Bristol, , United Kingdom

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University Hospital of Wales

Cardiff, , United Kingdom

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Ninewells Hospital

Dundee, , United Kingdom

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The Royal Marsden NHS Trust

London, , United Kingdom

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University College London

London, , United Kingdom

Site Status

Lancashire Teaching Hospitals NHS Foundation Trust Royal Preston Hospital

Preston, , United Kingdom

Site Status

Royal Marsden Hospital

Sutton, , United Kingdom

Site Status

Mid Yorkshire NHS Trust

Wakefield, , United Kingdom

Site Status

New Cross Hospital

Wolverhampton, , United Kingdom

Site Status

Countries

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China United States Argentina Australia Brazil Canada Czechia France Germany Israel Italy Japan Netherlands Poland Russia South Korea Spain Taiwan United Kingdom

References

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Ravi P, Kwak L, Xie W, Kelleher K, Acosta AM, McKay RR, Kibel AS, Taplin ME. Neoadjuvant Novel Hormonal Therapy Followed by Prostatectomy versus Up-Front Prostatectomy for High-Risk Prostate Cancer: A Comparative Analysis. J Urol. 2022 Oct;208(4):838-845. doi: 10.1097/JU.0000000000002803. Epub 2022 Sep 9.

Reference Type DERIVED
PMID: 36082554 (View on PubMed)

Other Identifiers

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2018-001746-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-506153-38-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

56021927PCR3011

Identifier Type: OTHER

Identifier Source: secondary_id

CR108535

Identifier Type: -

Identifier Source: org_study_id