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
4 other identifiers
interventional
2,517
18 countries
203
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jun 2019
Longer than P75 for phase_3
203 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 5, 2018
CompletedFirst Posted
Study publicly available on registry
December 6, 2018
CompletedStudy Start
First participant enrolled
June 11, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 13, 2028
April 13, 2026
April 1, 2026
7.5 years
December 5, 2018
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
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 Outcomes (10)
Prostate Specific Antigen (PSA)-Free Survival
Approximately 4 years
Event Free Survival (EFS)
Up to 7 years and 5 months
Time to Subsequent First Treatments (TTST-1)
Up to 7 years and 5 months
Time to Distant Metastasis (TTDM)
Up to 7 years and 5 months
MFS Based on Conventional Imaging
Up to 7 years and 5 months
- +5 more secondary outcomes
Study Arms (2)
Apalutamide + ADT
EXPERIMENTALParticipants 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.
Placebo + ADT
EXPERIMENTALParticipants 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.
Interventions
Participants will receive apalutamide 240 mg (4 tablets of 60 mg each) orally once daily.
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 \[ng/dL\]).
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- (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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (203)
UC San Diego Moores Cancer Center
La Jolla, California, 92093, United States
University of Southern California
Los Angeles, California, 90033, United States
Cedars Sinai Medical Center
Los Angeles, California, 90048, United States
University of California Los Angeles
Los Angeles, California, 90095, United States
University of California Irvine Medical Center Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
UC Davis Medical Center
Sacramento, California, 95817, United States
AdventHealth Medical Group Urology of Denver
Denver, Colorado, 80210, United States
Colorado Clinical Research
Lakewood, Colorado, 80228, United States
Stamford Hospital
Stamford, Connecticut, 06904, United States
Urology Specialists LLC
Hialeah, Florida, 33002, United States
Mayo Clinic - Division Of Hematology/oncology
Jacksonville, Florida, 32224, United States
Miami Cancer Institute at Baptist Health / Baptist Health Medical Group
Miami, Florida, 33176, United States
Advent Health
Orlando, Florida, 32804, United States
Emory University Winship Cancer Institute
Atlanta, Georgia, 30322-1013, United States
University of Chicago
Chicago, Illinois, 60637, United States
Ochsner LSU Health Shreveport - Regional Urology
Shreveport, Louisiana, 71106, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02115, United States
Beth Isreal Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Michigan Institute of Urology, PC
Troy, Michigan, 48084, United States
Saint Louis University
St Louis, Missouri, 63110, United States
Urology Cancer Center, PC
Omaha, Nebraska, 68130, United States
Albany Medical College
Albany, New York, 12208, United States
Great Lakes Physician PC d/b/a Western New York Urology Associates
Cheektowaga, New York, 14225, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065, United States
Weill Cornell Medical College
New York, New York, 10065, United States
SUNY Upstate Medical University
Syracuse, New York, 13210, United States
University of North Carolina
Chapel Hill, North Carolina, 27599, United States
Duke University School of Medicine
Durham, North Carolina, 27705, United States
Medication Management LLC
Greensboro, North Carolina, 27403, United States
Carolina Urology Partners, PLLC
Huntersville, North Carolina, 28078, United States
Cleveland VA Medical Center
Cleveland, Ohio, 44106, United States
Oklahoma City VAMC
Oklahoma City, Oklahoma, 73104, United States
MidLantic Urology
Bala-Cynwyd, Pennsylvania, 19004, United States
Omega Medical Research
Warwick, Rhode Island, 02886, United States
Ralph H. Johnson Veterans Affairs Medical Center
Charleston, South Carolina, 29401, United States
Medical University of South Carolina
Charleston, South Carolina, 29403, United States
Greenville Health
Greenville, South Carolina, 29605, United States
Carolina Urologic Research Center
Myrtle Beach, South Carolina, 29572, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
VA North Texas Health Care System
Dallas, Texas, 75216, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
Virginia Urology
Richmond, Virginia, 23235, United States
Urology of Virginia, PLCC
Virginia Beach, Virginia, 23462, United States
CAMC Memorial Hospital, Charleston Area Medical Center Physicians
Charleston, West Virginia, 25304, United States
Hospital Aleman
Caba, 1118, Argentina
Hospital Italiano de Buenos Aires
Ciudad Autonoma de, C1199ABB, Argentina
Centro Urologico Profesor Bengio
Córdoba, X5000KPH, Argentina
Cemaic Centro Privado de Especialidades Medicas Ambulatorias e Investigacion Clinica
Córdoba, X5008AAC, Argentina
Uroclinica
Mendoza, 5500, Argentina
Clinica Mayo de UMCB
San Miguel de Tucumán, 4000, Argentina
Eastern Health - Box Hill Hospital
Box Hill, 3128q, Australia
St Vincent s Hospital Sydney
Darlinghurst, 2010, Australia
Austin Health
Heidelberg, 3084, Australia
Australian Urology Associates Pty Ltd
Malvern, 3144, Australia
Royal Melbourne Hospital
Parkville, 3052, Australia
Northern Cancer Institute
St Leonards, 2065, Australia
Sydney Adventist Hospital
Wahroonga, 2076, Australia
Westmead Hospital
Westmead, 2145, Australia
Princess Alexandra Hospital
Woolloongabba, 4102, Australia
Associacao de Combate ao Cancer em Goias - Hospital de Cancer Araujo Jorge
Goiânia, 74605-070, Brazil
Oncosite - Centro de Pesquisa Clínica em Oncologia Ltda
Ijuí, 98700-000, Brazil
Liga Norte Riograndense Contra O Cancer
Natal, 59075-740, Brazil
Irmandade Santa Casa de Misericordia de Porto Alegre
Porto Alegre, 90020-090, Brazil
Universidade do Estado do Rio de Janeiro - UERJ
Rio de Janeiro, 20551-030, Brazil
Associacao Umane
São Paulo, 01232-910, Brazil
Fundacao Faculdade de Medicina - Instituto do Cancer do Estado de Sao Paulo
São Paulo, 01246 000, Brazil
Instituto Do Cancer Brasil
Três Lagoas, 79601-001, Brazil
Prostate Cancer Centre
Calgary, Alberta, T2V 1P9, Canada
Vancouver Prostate Centre, Gordon and Leslie Diamond Health Care Centre
Vancouver, British Columbia, V5Z 1M9, Canada
Nova Scotia Health Authority
Halifax, Nova Scotia, B3H 2Y9, Canada
London Health Sciences Center
London, Ontario, N6A 5W9, Canada
Sunnybrook Health Sciences Center
Toronto, Ontario, M4N 3M5, Canada
Princess Margaret Cancer Centre University Health Network
Toronto, Ontario, M5G2M9, Canada
CHUM - Centre hospitalier universitaire de Montreal
Montreal, Quebec, H2X 0A9, Canada
CHU de Quebec Universite Laval Hopital de l Enfant Jesus
Québec, Quebec, G1R 2J6, Canada
Fakultni nemocnice Hradec Kralove
Hradec Králove, 500 05, Czechia
Krajská nemocnice Liberec
Liberec, 460 63, Czechia
Uromedical Center s.r.o.
Olomouc, 77200, Czechia
Fakultni nemocnice Plzen, Urologicka klinika
Pilsen, 305 99, Czechia
Vseobecna fakultni nemocnice v Praze
Prague, 120 00, Czechia
Thomayerova nemocnice
Prague, 140 59, Czechia
CHU d'Angers
Angers, 49933, France
CHRU Besancon Hopital Jean Minjoz
Besançon, 25030, France
Hopital Pellegrin CHU Bordeaux
Bordeaux, 33076, France
APHP - Hopital Henri Mondor
Créteil, 94010, France
Hopital Edouard Herriot - CHU Lyon
Lyon, 69437, France
CHU de Nantes hotel Dieu
Nantes, 44000, France
Institut Mutualiste Montsouris
Paris, 75014, France
Clinique de la Croix du Sud
Quint-Fonsegrives, 31130, France
Chu Rennes Hopital Pontchaillou
Rennes, 35033, France
CHU de Toulouse - Hôpital Rangueil
Toulouse, 31059, France
CHRU Tours Hopital Bretonneau
Tours, 37000, France
Universitaetsklinikum der RWTH Aachen
Aachen, 52074, Germany
Stadtisches Klinikum Braunschweig gGmbH-Klinik fur Urologie und Uroonkologie
Braunschweig, 38126, Germany
Universitaetsklinikum Koelnt
Cologne, 50937, Germany
Praxis Dr. med. Ralf Eckert
Eisleben Lutherstadt, 06295, Germany
Universitatsklinikum Essen
Essen, 45147, Germany
Universitatsklinikum Frankfurt
Frankfurt am Main, 60590, Germany
Prostata zentrum Nordwest
Gronau, 48599, Germany
Martini-Klinik am Universitätsklinikum Hamburg-Eppendorf Urologie
Hamburg, 20246, Germany
Universitätsklinikum des Saarlandes
Homburg/Saar, 66421, Germany
Universitatsklinikum Schleswig Holstein Campus Lubeck
Lübeck, 23538, Germany
Klinikum St. Elisabeth Straubing GmbH
Straubing, 94315, Germany
Kliniken Nordoberpfalz, Klinik für Urologie
Weiden/Opf, 92637, Germany
Praxisgemeinschaft f. Onkologie u. Urologie - Germany
Wilhelmshaven, 26389, Germany
Asaf Harofe Medical Center
Beer Yaakov, 60930, Israel
Rambam Health Care Campus
Haifa, 31096, Israel
Tel Aviv University Sackler School of Medicine - Meir Medical Center (MMC)
Kfar Saba, 4428164, Israel
Rabin Medical Center
Petah Tikva, 49100, Israel
The Chaim Sheba Medical Center
Ramat Gan, 52621, Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, 64239, Israel
Policlinico Abano Terme
Abano Terme, 35031, Italy
Generale Regionale F. Miulli
Acquaviva delle Fonti, 70021, Italy
Ospedale di Bassano del Grappa
Bassano del Grappa, 36061, Italy
ASST Spedali Civili Brescia
Brescia, 25123, Italy
ASL2 Lanciano - Vasto - Chieti - Ospedale 'SS Annunziata' di Chieti
Chieti, 66100, Italy
Azienda Ospedaliero Universitaria Careggi
Florence, 50134, Italy
San Raffaele Turro - Istituto di Ricovero e Cura a Carattere Scientifico
Milan, 20127, Italy
Ospedale San Raffaele
Milan, 20132, Italy
Istituto Europeo di Oncologia
Milan, 20141, Italy
Clinica di Urologia Policlinico di Modena - Universita di Modena e reggio Emilia
Modena, 41100, Italy
Università del Piemonte Orientale - Ospedale Maggiore della Carità di Novara
Novara, 28100, Italy
Universita degli Studi di Torino - Azienda Ospedaliero-Universitaria San Luigi Gonzaga
Orbassano, 10043, Italy
Universita Campus Bio-Medico di Roma
Roma, 00128, Italy
Istituto Nazionale Tumori Regina Elena
Roma, 00144, Italy
Azienda Ospedaliera Sant Andrea
Roma, 00189, Italy
Ospedale Molinette, AO Città della Salute e della Scienza di
Torino, 10126, Italy
UOC di Urologia AOU Integrata di Verona - Polo Chirurgico Confortini - Ospedale Borgo Trento
Verona, 37126, Italy
Akita University Hospital
Akita, 010-8543, Japan
Chiba University Hospital
Chiba, 260 8677, Japan
Chiba Cancer Center
Chūōku, 260-8717, Japan
Hakodate Goryoukaku Hospital
Hakodate, 040 8611, Japan
Hirosaki University Hospital
Hirosaki, 036-8203, Japan
Kanazawa University Hospital
Kanazawa, 920 8641, Japan
Kobe City Medical Center General Hospital
Kobe, 650-0047, Japan
Dokkyo Medical University Saitama Medical Center
Koshigaya, 343-8555, Japan
Kurume University Hospital
Kurume, 830-0011, Japan
Kyoto University Hospital
Kyoto, 606-8507, Japan
National Hospital Organization Shikoku Cancer Center
Matsuyama, 791-0280, Japan
Kitasato University Hospital
Minamiku, 252-0375, Japan
University of Miyazaki Hospital
Miyazaki, 889-1692, Japan
Nagano Municipal Hospital
Nagano, 381-8551, Japan
Osaka International Cancer Institute
Osaka, 541 8567, Japan
Kindai University Hospital
Sakai, 590 0197, Japan
Toho University Sakura Medical Center
Sakura, 285-8741, Japan
Hokkaido University Hospital
Sapporo, 060-8648, Japan
Iwate Medical University Hospital
Shiwa-gun, 028-3695, Japan
Nippon Medical School Hospital
Tokyo, 113 8603, Japan
Juntendo University Hospital
Tokyo, 113-8421, Japan
Yamaguchi University Hospital
Ube, 755-8505, Japan
Yokohama City University Medical Center
Yokohama, 232 0024, Japan
Antoni van Leeuwenhoek
Amsterdam, 1066 CX, Netherlands
Catharinaziekenhuis
Eindhoven, 5623 EJ, Netherlands
St. Antonius Ziekenhuis (St. Antonius Hospital)
Nieuwegein, 3430EM, Netherlands
Canisius-Wilhelmina Ziekenhuis
Nijmegen, 6524 KD, Netherlands
Samodzielny Publiczny Wielospecjalistyczny Zaklad Opieki Zdrowotnej Mswia W Bydgoszczy
Bydgoszcz, 85 015, Poland
Szpital Uniwersytecki NR 1 IM Dr Antoniego Jurasza
Bydgoszcz, 85 094, Poland
Szpital Wojewodzki im Mikolaja Kopernika w Koszalinie
Koszalin, 75 581, Poland
Pratia MCM Krakow
Krakow, 30-727, Poland
City Clinic Sp. z o.o.
Warsaw, 02-473, Poland
Dolnoslaskie Centrum Onkologii, Oddzial Chirurgii Onkologicznej II - Urologia
Wroclaw, 53-413, Poland
Altai Regional Oncology Dispensary
Barnaul, 656049, Russia
Chelyabinsk Regional Clinical Center Of Oncology And Nuclear Medicine
Chelyabinsk, 454087, Russia
Moscow City Clinical Hospital # 62
Moscow, 125130, Russia
Hertzen Oncology Research Institute
Moscow, 125284, Russia
Clinical Oncology Dispensary
Omsk, 644013, Russia
Medical-sanitary unit 'Neftyanik'
Tyumen, 625000, Russia
Vologda Regional Oncological Dispensary
Vologda, 160012, Russia
Chonnam National University Hospital
Gwangju, 61469, South Korea
Seoul National University Bundang Hospital
Gyeonggi-do, 13605, South Korea
Severance Hospital Yonsei University Health System
Seoul, 03722, South Korea
Asan Medical Center 1
Seoul, 05505, South Korea
Asan Medical Center
Seoul, 05505, South Korea
The Catholic University of Korea Seoul St Marys Hospital
Seoul, 06591, South Korea
Hosp Univ A Coruna
A Coruña, 15006, Spain
Hosp Univ Vall D Hebron
Barcelona, 8035, Spain
Hosp. Puerta Del Mar
Cadiz, 11009, Spain
Hosp. Gral. Univ. de Castellon
Castellon, 12004, Spain
Hosp. de Jerez de La Frontera
Jerez de la Frontera, 11407, Spain
Hosp. Univ. Ramon Y Cajal
Madrid, 28034, Spain
Hosp. Univ. 12 de Octubre
Madrid, 28041, Spain
Hosp. Univ. La Paz
Madrid, 28046, Spain
Fund. Hosp. de Manacor
Manacor, 07500, Spain
Hosp Virgen de La Victoria
Málaga, 29010, Spain
Hosp. Univ. Marques de Valdecilla
Santander, 39008, Spain
Hosp. Virgen Del Rocio
Seville, 41013, Spain
Inst. Valenciano de Oncologia
Valencia, 46009, Spain
Hosp. Clinico Univ. de Valencia
Valencia, 46010, Spain
Kaohsiung Medical University Chung Ho Memorial Hospital
Kaohsiung City, 807, Taiwan
China Medical University Hospital
Taichung, 40447, Taiwan
Taichung Veterans General Hospital
Taichung, 40705, Taiwan
Tungs' Taichung MetroHarbor Hospital
Taichung, 435, Taiwan
Chi Mei Medical Center Yong Kang
Tainan, 710, Taiwan
National Taiwan University Hospital.
Taipei, 10002, Taiwan
Southmead Hospital
Bristol, BS10 5NB, United Kingdom
University Hospital of Wales
Cardiff, CF14 4XW, United Kingdom
Ninewells Hospital
Dundee, DD2 1UB, United Kingdom
The Royal Marsden NHS Trust
London, SW3 6JJ, United Kingdom
University College London
London, WC1E 6BT, United Kingdom
Lancashire Teaching Hospitals NHS Foundation Trust Royal Preston Hospital
Preston, PR2 9HT, United Kingdom
Royal Marsden Hospital
Sutton, SM2 5PT, United Kingdom
Mid Yorkshire NHS Trust
Wakefield, WF1 4DG, United Kingdom
New Cross Hospital
Wolverhampton, WV10 0QP, United Kingdom
Related Publications (1)
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.
PMID: 36082554DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Janssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 5, 2018
First Posted
December 6, 2018
Study Start
June 11, 2019
Primary Completion (Estimated)
December 1, 2026
Study Completion (Estimated)
October 13, 2028
Last Updated
April 13, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
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