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

A Randomized, Double-blind, Placebo-controlled, Phase 3 Study of Apalutamide in Subjects With High-risk, Localized or Locally Advanced Prostate Cancer Who Are Candidates for Radical Prostatectomy

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Prostatic Neoplasms
• Intervention / Treatment: Drug: Apalutamide; Drug: Androgen Deprivation Therapy (ADT); Drug: Placebo

Detailed Description

High-risk prostate cancer accounts for approximately 15 percent (%) of newly diagnosed prostate cancers. A systemic therapy that eradicates micrometastatic disease is needed to improve survival in high-risk participants undergoing RP with pLND. It is hypothesized that androgen blockade prior to and after RP with pLND may improve outcomes for participants at the highest risk for recurrence. This study is designed to evaluate if androgen blockade administered prior to and after RP with pLND will increase the rate of pathological complete response (pCR) and lead to better overall outcomes. ERLEADA (apalutamide, also known as JNJ-56021927 and ARN-509) is an orally available, non-steroidal small molecule, which acts as a potent and selective antagonist of the androgen receptor (AR), currently being developed for the treatment of prostate cancer. The study includes screening phase (approximately up to 35 days before randomization), treatment phase (the planned Treatment Phase will include a total of 12 treatment cycles of apalutamide or placebo; 6 cycles prior to RP with pLND (Cycle 1 through Cycle 6) and 6 cycles after RP with pLND (Cycle 7 through Cycle 12). Cycle 1 Day 1 will start within 3 days after randomization) and follow-up phase. The end of study (study completion) is defined as last participant assessment at study site with approximate study duration of 8 years. Participants will undergo efficacy, pharmacokinetics and biomarker evaluations. The safety will be monitored throughout the study. An open-label sub-study comparing apalutamide plus ADT before and after RP with pLND with standard of care treatment will be initiated at selected sites upon notification by the sponsor.

• Study Type: Interventional
• Enrollment (Actual): 2517
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Caba, Argentina, 1118
    • Hospital Aleman
  • Ciudad Autonoma de, Argentina, C1199ABB
    • Hospital Italiano de Buenos Aires
  • Córdoba, Argentina, X5000KPH
    • Centro Urologico Profesor Bengio
  • Córdoba, Argentina, X5008AAC
    • Cemaic Centro Privado de Especialidades Medicas Ambulatorias e Investigacion Clinica
  • Mendoza, Argentina, 5500
    • Uroclinica
  • San Miguel de Tucumán, Argentina, 4000
    • Clinica Mayo de UMCB
• Australia
  • Box Hill, Australia, 3128q
    • Eastern Health - Box Hill Hospital
  • Darlinghurst, Australia, 2010
    • St Vincent s Hospital Sydney
  • Heidelberg, Australia, 3084
    • Austin Health
  • Malvern, Australia, 3144
    • Australian Urology Associates Pty Ltd
  • Parkville, Australia, 3052
    • Royal Melbourne Hospital
  • St Leonards, Australia, 2065
    • Northern Cancer Institute
  • Wahroonga, Australia, 2076
    • Sydney Adventist Hospital
  • Westmead, Australia, 2145
    • Westmead Hospital
  • Woolloongabba, Australia, 4102
    • Princess Alexandra Hospital
• Brazil
  • Goiânia, Brazil, 74605-070
    • Associacao de Combate ao Cancer em Goias - Hospital de Cancer Araujo Jorge
  • Ijuí, Brazil, 98700-000
    • Oncosite - Centro de Pesquisa Clínica em Oncologia Ltda
  • Natal, Brazil, 59075-740
    • Liga Norte Riograndense Contra O Cancer
  • Porto Alegre, Brazil, 90020-090
    • Irmandade Santa Casa de Misericordia de Porto Alegre
  • Rio de Janeiro, Brazil, 20551-030
    • Universidade do Estado do Rio de Janeiro - UERJ
  • São Paulo, Brazil, 01246 000
    • Fundacao Faculdade de Medicina - Instituto do Cancer do Estado de Sao Paulo
  • São Paulo, Brazil, 01232-910
    • Associacao Umane
  • Três Lagoas, Brazil, 79601-001
    • Instituto Do Cancer Brasil
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2V 1P9
      • Prostate Cancer Centre
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver Prostate Centre, Gordon and Leslie Diamond Health Care Centre
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Nova Scotia Health Authority
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Center
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Center
    • Toronto, Ontario, Canada, M5G2M9
      • Princess Margaret Cancer Centre University Health Network
  • Quebec
    • Montreal, Quebec, Canada, H2X 0A9
      • CHUM - Centre hospitalier universitaire de Montreal
    • Québec, Quebec, Canada, G1R 2J6
      • CHU de Quebec Universite Laval Hopital de l Enfant Jesus
• Czechia
  • Hradec Králove, Czechia, 500 05
    • Fakultni nemocnice Hradec Kralove
  • Liberec, Czechia, 460 63
    • Krajská nemocnice Liberec
  • Olomouc, Czechia, 77200
    • Uromedical Center s.r.o.
  • Pilsen, Czechia, 305 99
    • Fakultni nemocnice Plzen, Urologicka klinika
  • Prague, Czechia, 140 59
    • Thomayerova nemocnice
  • Prague, Czechia, 120 00
    • Všeobecná fakultní nemocnice v Praze
• France
  • Angers, France, 49933
    • CHU d'Angers
  • Besançon, France, 25030
    • CHRU Besancon Hopital Jean Minjoz
  • Bordeaux, France, 33076
    • Hopital Pellegrin CHU Bordeaux
  • Créteil, France, 94010
    • APHP - Hopital Henri Mondor
  • Lyon, France, 69437
    • Hopital Edouard Herriot - CHU Lyon
  • Nantes, France, 44000
    • CHU de Nantes hotel Dieu
  • Paris, France, 75014
    • Institut Mutualiste Montsouris
  • Quint-Fonsegrives, France, 31130
    • Clinique de la Croix du Sud
  • Rennes, France, 35033
    • Chu Rennes Hopital Pontchaillou
  • Toulouse, France, 31059
    • CHU de Toulouse - Hôpital Rangueil
  • Tours, France, 37000
    • CHRU Tours Hopital Bretonneau
• Germany
  • Aachen, Germany, 52074
    • Universitaetsklinikum der RWTH Aachen
  • Braunschweig, Germany, 38126
    • Stadtisches Klinikum Braunschweig gGmbH-Klinik fur Urologie und Uroonkologie
  • Cologne, Germany, 50937
    • Universitaetsklinikum Koelnt
  • Eisleben Lutherstadt, Germany, 06295
    • Praxis Dr. med. Ralf Eckert
  • Essen, Germany, 45147
    • Universitätsklinikum Essen
  • Frankfurt am Main, Germany, 60590
    • Universitatsklinikum Frankfurt
  • Gronau, Germany, 48599
    • Prostata zentrum Nordwest
  • Hamburg, Germany, 20246
    • Martini-Klinik am Universitätsklinikum Hamburg-Eppendorf Urologie
  • Homburg/Saar, Germany, 66421
    • Universitätsklinikum des Saarlandes
  • Lübeck, Germany, 23538
    • Universitatsklinikum Schleswig Holstein Campus Lubeck
  • Straubing, Germany, 94315
    • Klinikum St. Elisabeth Straubing GmbH
  • Weiden/Opf, Germany, 92637
    • Kliniken Nordoberpfalz, Klinik für Urologie
  • Wilhelmshaven, Germany, 26389
    • Praxisgemeinschaft f. Onkologie u. Urologie - Germany
• Israel
  • Beer Yaakov, Israel, 60930
    • Asaf Harofe Medical Center
  • Haifa, Israel, 31096
    • Rambam Health Care Campus
  • Kfar Saba, Israel, 4428164
    • Tel Aviv University Sackler School of Medicine - Meir Medical Center (MMC)
  • Petah Tikva, Israel, 49100
    • Rabin Medical Center
  • Ramat Gan, Israel, 52621
    • The Chaim Sheba Medical Center
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center
• Italy
  • Abano Terme, Italy, 35031
    • Policlinico Abano Terme
  • Acquaviva delle Fonti, Italy, 70021
    • Generale Regionale F. Miulli
  • Bassano del Grappa, Italy, 36061
    • Ospedale di Bassano del Grappa
  • Brescia, Italy, 25123
    • ASST Spedali Civili Brescia
  • Chieti, Italy, 66100
    • ASL2 Lanciano - Vasto - Chieti - Ospedale 'SS Annunziata' di Chieti
  • Florence, Italy, 50134
    • Azienda Ospedaliero Universitaria Careggi
  • Milan, Italy, 20132
    • Ospedale San Raffaele
  • Milan, Italy, 20141
    • Istituto Europeo di Oncologia
  • Milan, Italy, 20127
    • San Raffaele Turro - Istituto di Ricovero e Cura a Carattere Scientifico
  • Modena, Italy, 41100
    • Clinica di Urologia Policlinico di Modena - Universita di Modena e reggio Emilia
  • Novara, Italy, 28100
    • Università del Piemonte Orientale - Ospedale Maggiore della Carità di Novara
  • Orbassano, Italy, 10043
    • Universita degli Studi di Torino - Azienda Ospedaliero-Universitaria San Luigi Gonzaga
  • Roma, Italy, 00144
    • Istituto Nazionale Tumori Regina Elena
  • Roma, Italy, 00189
    • Azienda Ospedaliera Sant Andrea
  • Roma, Italy, 00128
    • Universita Campus Bio-Medico di Roma
  • Torino, Italy, 10126
    • Ospedale Molinette, AO Città della Salute e della Scienza di
  • Verona, Italy, 37126
    • UOC di Urologia AOU Integrata di Verona - Polo Chirurgico Confortini - Ospedale Borgo Trento
• Japan
  • Akita, Japan, 010-8543
    • Akita University Hospital
  • Chiba, Japan, 260 8677
    • Chiba University Hospital
  • Chūōku, Japan, 260-8717
    • Chiba Cancer Center
  • Hakodate, Japan, 040 8611
    • Hakodate Goryoukaku Hospital
  • Hirosaki, Japan, 036-8203
    • Hirosaki University Hospital
  • Kanazawa, Japan, 920 8641
    • Kanazawa University Hospital
  • Kobe, Japan, 650-0047
    • Kobe City Medical Center General Hospital
  • Koshigaya, Japan, 343-8555
    • Dokkyo Medical University Saitama Medical Center
  • Kurume, Japan, 830-0011
    • Kurume University Hospital
  • Kyoto, Japan, 606-8507
    • Kyoto University Hospital
  • Matsuyama, Japan, 791-0280
    • National Hospital Organization Shikoku Cancer Center
  • Minamiku, Japan, 252-0375
    • Kitasato University Hospital
  • Miyazaki, Japan, 889-1692
    • University of Miyazaki Hospital
  • Nagano, Japan, 381-8551
    • Nagano Municipal Hospital
  • Osaka, Japan, 541 8567
    • Osaka International Cancer Institute
  • Sakai, Japan, 590 0197
    • Kindai University Hospital
  • Sakura, Japan, 285-8741
    • Toho University Sakura Medical Center
  • Sapporo, Japan, 060-8648
    • Hokkaido University Hospital
  • Shiwa-gun, Japan, 028-3695
    • Iwate Medical University Hospital
  • Tokyo, Japan, 113-8421
    • Juntendo University Hospital
  • Tokyo, Japan, 113 8603
    • Nippon Medical School Hospital
  • Ube, Japan, 755-8505
    • Yamaguchi University Hospital
  • Yokohama, Japan, 232 0024
    • Yokohama City University Medical Center
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Antoni van Leeuwenhoek
  • Eindhoven, Netherlands, 5623 EJ
    • Catharinaziekenhuis
  • Nieuwegein, Netherlands, 3430EM
    • St. Antonius Ziekenhuis (St. Antonius Hospital)
  • Nijmegen, Netherlands, 6524 KD
    • Canisius-Wilhelmina Ziekenhuis
• Poland
  • Bydgoszcz, Poland, 85 094
    • Szpital Uniwersytecki NR 1 IM Dr Antoniego Jurasza
  • Bydgoszcz, Poland, 85 015
    • Samodzielny Publiczny Wielospecjalistyczny Zaklad Opieki Zdrowotnej Mswia W Bydgoszczy
  • Koszalin, Poland, 75 581
    • Szpital Wojewodzki im Mikolaja Kopernika w Koszalinie
  • Krakow, Poland, 30-727
    • Pratia MCM Krakow
  • Warsaw, Poland, 02-473
    • City Clinic Sp. z o.o.
  • Wroclaw, Poland, 53-413
    • Dolnoslaskie Centrum Onkologii, Oddzial Chirurgii Onkologicznej II - Urologia
• Russia
  • Barnaul, Russia, 656049
    • Altai Regional Oncology Dispensary
  • Chelyabinsk, Russia, 454087
    • Chelyabinsk Regional Clinical Center Of Oncology And Nuclear Medicine
  • Moscow, Russia, 125130
    • Moscow City Clinical Hospital # 62
  • Moscow, Russia, 125284
    • Hertzen Oncology Research Institute
  • Omsk, Russia, 644013
    • Clinical Oncology Dispensary
  • Tyumen, Russia, 625000
    • Medical-sanitary unit 'Neftyanik'
  • Vologda, Russia, 160012
    • Vologda Regional Oncological Dispensary
• South Korea
  • Gwangju, South Korea, 61469
    • Chonnam National University Hospital
  • Gyeonggi-do, South Korea, 13605
    • Seoul National University Bundang Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital Yonsei University Health System
  • Seoul, South Korea, 06591
    • The Catholic University of Korea Seoul St Marys Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center 1
• Spain
  • A Coruña, Spain, 15006
    • Hosp Univ A Coruna
  • Barcelona, Spain, 8035
    • Hosp Univ Vall D Hebron
  • Cadiz, Spain, 11009
    • Hosp. Puerta Del Mar
  • Castellon, Spain, 12004
    • Hosp. Gral. Univ. de Castellon
  • Jerez de la Frontera, Spain, 11407
    • Hosp. de Jerez de La Frontera
  • Madrid, Spain, 28041
    • Hosp. Univ. 12 de Octubre
  • Madrid, Spain, 28034
    • Hosp. Univ. Ramon Y Cajal
  • Madrid, Spain, 28046
    • Hosp. Univ. La Paz
  • Manacor, Spain, 07500
    • Fund. Hosp. de Manacor
  • Málaga, Spain, 29010
    • Hosp Virgen de La Victoria
  • Santander, Spain, 39008
    • Hosp. Univ. Marques de Valdecilla
  • Seville, Spain, 41013
    • Hosp. Virgen Del Rocio
  • Valencia, Spain, 46009
    • Inst. Valenciano de Oncologia
  • Valencia, Spain, 46010
    • Hosp. Clinico Univ. de Valencia
• Taiwan
  • Kaohsiung City, Taiwan, 807
    • Kaohsiung Medical University Chung Ho Memorial Hospital
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Taichung, Taiwan, 435
    • Tungs' Taichung MetroHarbor Hospital
  • Tainan, Taiwan, 710
    • Chi Mei Medical Center Yong Kang
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
• United Kingdom
  • Bristol, United Kingdom, BS10 5NB
    • Southmead Hospital
  • Cardiff, United Kingdom, CF14 4XW
    • University Hospital of Wales
  • Dundee, United Kingdom, DD2 1UB
    • Ninewells Hospital
  • London, United Kingdom, WC1E 6BT
    • University College London
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden NHS Trust
  • Preston, United Kingdom, PR2 9HT
    • Lancashire Teaching Hospitals NHS Foundation Trust Royal Preston Hospital
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden Hospital
  • Wakefield, United Kingdom, WF1 4DG
    • Mid Yorkshire NHS Trust
  • Wolverhampton, United Kingdom, WV10 0QP
    • New Cross Hospital
• United States
  • California
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
    • Orange, California, United States, 92868
      • University of California Irvine Medical Center Chao Family Comprehensive Cancer Center
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
  • Colorado
    • Denver, Colorado, United States, 80210
      • AdventHealth Medical Group Urology of Denver
    • Lakewood, Colorado, United States, 80228
      • Colorado Clinical Research
  • Connecticut
    • Stamford, Connecticut, United States, 06904
      • Stamford Hospital
  • Florida
    • Hialeah, Florida, United States, 33002
      • Urology Specialists LLC
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic - Division Of Hematology/oncology
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute at Baptist Health / Baptist Health Medical Group
    • Orlando, Florida, United States, 32804
      • Advent Health
  • Georgia
    • Atlanta, Georgia, United States, 30322-1013
      • Emory University Winship Cancer Institute
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Louisiana
    • Shreveport, Louisiana, United States, 71106
      • Ochsner LSU Health Shreveport - Regional Urology
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02215
      • Beth Isreal Deaconess Medical Center
  • Michigan
    • Troy, Michigan, United States, 48084
      • Michigan Institute of Urology, PC
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Saint Louis University
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Urology Cancer Center, PC
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical College
    • Cheektowaga, New York, United States, 14225
      • Great Lakes Physician PC d/b/a Western New York Urology Associates
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University School of Medicine
    • Greensboro, North Carolina, United States, 27403
      • Medication Management LLC
    • Huntersville, North Carolina, United States, 28078
      • Carolina Urology Partners, PLLC
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Cleveland VA Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma City VAMC
  • Pennsylvania
    • Bala-Cynwyd, Pennsylvania, United States, 19004
      • MidLantic Urology
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • Omega Medical Research
  • South Carolina
    • Charleston, South Carolina, United States, 29403
      • Medical University of South Carolina
    • Charleston, South Carolina, United States, 29401
      • Ralph H. Johnson Veterans Affairs Medical Center
    • Greenville, South Carolina, United States, 29605
      • Greenville Health
    • Myrtle Beach, South Carolina, United States, 29572
      • Carolina Urologic Research Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75216
      • VA North Texas Health Care System
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Virginia
    • Richmond, Virginia, United States, 23235
      • Virginia Urology
    • Virginia Beach, Virginia, United States, 23462
      • Urology of Virginia, PLCC
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • CAMC Memorial Hospital, Charleston Area Medical Center Physicians

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Apalutamide; Participants will receive apalutamide 240 mg (4 tablets of 60 mg each) orally once daily.; Other Names: JNJ-56021927; 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]).
Experimental: 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.	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]).; Drug: Placebo; Participants will receive matching placebo oral tablets daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with Pathologic complete response (pCR)	pCR is assessed by a pathology blinded independent central radiology review (BICR) as defined in the pathology charter.	Approximately 4 years
Metastasis-Free Survival (MFS)	MFS is defined as the time from randomization to the date of the occurrence of radiographic distant metastasis evaluated by radiology BICR, incidental pathologic finding of distant metastasis, or death from any cause, whichever occurs first.	Up to 7 years and 5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prostate Specific Antigen (PSA)-Free Survival	PSA-free survival with testosterone recovery defined as the time from randomization to the first detectable serum PSA level with recovered testosterone levels after undetectable PSA post-radical prostatectomy with pelvic lymph node dissection or death, whichever occurs first.	Approximately 4 years
Event Free Survival (EFS)	EFS defined as time from randomization to any of the following events: biochemical failure (BCF); or local or regional recurrence by BICR or histopathological assessment; or distant metastasis by BICR or histopathological assessment; or death.	Up to 7 years and 5 months
Time to Subsequent First Treatments (TTST-1)	TTST-1 is defined as the time from randomization to the date of first subsequent therapy.	Up to 7 years and 5 months
Time to Distant Metastasis (TTDM)	TTDM is defined as the time from the date of enrollment until the first date of distant metastasis.	Up to 7 years and 5 months
MFS Based on Conventional Imaging	MFS based on conventional imaging, defined as the time from randomization to the date of the first occurrence of radiographic distant metastasis on CT/MRI and bone scan by radiology BICR, pathologic finding of distant metastasis, or death from any cause, whichever occurs first.	Up to 7 years and 5 months
Number of Participants with Laboratory Abnormalities as a Measure of Safety and Tolerability	Blood samples for serum chemistry and hematology will be collected at predefined time points for clinical laboratory testing.	Up to 30 days after last dose of study drug (Approximately 8 years)
Number of Participants with Vital Signs Abnormalities as a Measure of Safety and Tolerability	Number of participants with vital signs (including body temperature, heart rate, respiratory rate, and blood pressure) abnormalities will be reported.	Up to 30 days after last dose of study drug (Approximately 8 years)
Number of Participants with Physical Examinations Abnormalities as a Measure of Safety and Tolerability	Number of participants with physical examinations (including general appearance of the participant, height, weight, and examination of the skin, ears, nose, throat, lungs, heart, abdomen, extremities, musculoskeletal system, lymphatic system, and nervous system) abnormalities will be reported.	Up to 30 days after last dose of study drug (Approximately 8 years)
Number of Participants with Treatment Compliance Rate	Number of participants who are complaint with study treatment will be assessed.	Up to 30 days after last dose of study drug (Approximately 8 years)
Number of Participants with No Evidence of Disease (NED) at 4 Years	Number of participants with NED at 4 years will be reported. NED at 4 years is defined as: (a) alive, (b) Undetectable prostate-specific antigen (PSA), (c) No distant metastasis, (d) No local or regional recurrence, (e) No subsequent therapy for prostate cancer, (f) Testosterone recovery to physiological testosterone levels, defined as 200 nanograms per deciliter (ng/dL).	Up to 4 years

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Publications and helpful links

General Publications

• 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.
• Taplin ME, Gleave M, Shore ND, Lopez-Gitlitz A, Kretschmer A, Efstathiou E, Nguyen PL, Damiao R, Kamoto T, Ross A, Briganti A, Hadaschik BA, Heidenreich A, Juarez Soto A, Ye H, Gotto G, Rooney B, Tian SK, Wetherhold L, Miladinovic B, McCarthy SA, Evans CP, Kibel AS; PROTEUS Investigators. Perioperative Apalutamide in High-Risk Localized Prostate Cancer. N Engl J Med. 2026 May 31. doi: 10.1056/NEJMoa2603878. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2019
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): October 13, 2028

Study Registration Dates

• First Submitted: December 5, 2018
• First Submitted That Met QC Criteria: December 5, 2018
• First Posted (Actual): December 6, 2018

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Pharmacologic Actions; Chemical Actions and Uses; Androgen Antagonists; apalutamide
• Other Study ID Numbers: CR108535; 56021927PCR3011 (Other Identifier: Janssen Research & Development, LLC); 2018-001746-34 (EudraCT Number); 2023-506153-38-00 (Registry Identifier: EUCT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of Johnson & Johnson Innovative Medicine is available at innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No