Clinical trial NCT03767244: A Study of Apalutamide in Participants With High-Risk, Localized or Locally Advanced Prostate Cancer Who Are Candidates for Radical Prostatectomy
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Prostatic Neoplasms
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2018-12-06
Enrollment: 2517
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants with Pathologic complete response (pCR)
timeFrame: Approximately 4 years
measure: Metastasis-Free Survival (MFS)
timeFrame: Up to 7 years and 5 months
Secondary outcomes:
measure: Prostate Specific Antigen (PSA)-Free Survival
timeFrame: Approximately 4 years
measure: Event Free Survival (EFS)
timeFrame: Up to 7 years and 5 months
measure: Time to Subsequent First Treatments (TTST-1)
timeFrame: Up to 7 years and 5 months
measure: Time to Distant Metastasis (TTDM)
timeFrame: Up to 7 years and 5 months
measure: MFS Based on Conventional Imaging
timeFrame: Up to 7 years and 5 months
measure: Number of Participants with No Evidence of Disease (NED) at 4 Years
timeFrame: Up to 4 years
measure: Number of Participants with Vital Signs Abnormalities as a Measure of Safety and Tolerability
timeFrame: Up to 30 days after last dose of study drug (Approximately 8 years)
measure: Number of Participants with Physical Examinations Abnormalities as a Measure of Safety and Tolerability
timeFrame: Up to 30 days after last dose of study drug (Approximately 8 years)
measure: Number of Participants with Laboratory Abnormalities as a Measure of Safety and Tolerability
timeFrame: Up to 30 days after last dose of study drug (Approximately 8 years)
measure: Number of Participants with Treatment Compliance Rate
timeFrame: Up to 30 days after last dose of study drug (Approximately 8 years)
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Orange
country: United States
facility: University of California Irvine Medical Center Chao Family Comprehensive Cancer Center
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: Denver
country: United States
facility: AdventHealth Medical Group Urology of Denver
state: Colorado
city: Lakewood
country: United States
facility: Colorado Clinical Research
state: Colorado
city: Stamford
country: United States
facility: Stamford Hospital
state: Connecticut
city: Hialeah
country: United States
facility: Urology Specialists LLC
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic - Division Of Hematology/oncology
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute at Baptist Health / Baptist Health Medical Group
state: Florida
city: Orlando
country: United States
facility: Florida Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory University Winship Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Shreveport
country: United States
facility: Ochsner LSU Health Shreveport - Regional Urology
state: Louisiana
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Beth Isreal Deaconess Medical Center
state: Massachusetts
city: Troy
country: United States
facility: Michigan Institute of Urology, PC
state: Michigan
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Omaha
country: United States
facility: Urology Cancer Center, PC
state: Nebraska
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Cheektowaga
country: United States
facility: Great Lakes Physician PC d/b/a Western New York Urology Associates
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke University School of Medicine
state: North Carolina
city: Greensboro
country: United States
facility: Medication Management LLC
state: North Carolina
city: Huntersville
country: United States
facility: Carolina Urology Partners, PLLC
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland VA Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma City VAMC
state: Oklahoma
city: Bala-Cynwyd
country: United States
facility: MidLantic Urology
state: Pennsylvania
city: Warwick
country: United States
facility: Omega Medical Research
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Charleston
country: United States
facility: Ralph H. Johnson Veterans Affairs Medical Center
state: South Carolina
city: Greenville
country: United States
facility: Greenville Health
state: South Carolina
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: VA North Texas Health Care System
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Richmond
country: United States
facility: Virginia Urology
state: Virginia
city: Virginia Beach
country: United States
facility: Urology of Virginia, PLCC
state: Virginia
city: Charleston
country: United States
facility: CAMC Memorial Hospital, Charleston Area Medical Center Physicians
state: West Virginia
city: Caba
country: Argentina
facility: Hospital Aleman
city: Ciudad Autonoma de
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Cordoba
country: Argentina
facility: Cemaic Centro Privado de Especialidades Medicas Ambulatorias e Investigacion Clinica
city: Cordoba
country: Argentina
facility: Centro Urologico Profesor Bengio
city: Mendoza
country: Argentina
facility: Uroclinica
city: San Miguel de Tucuman
country: Argentina
facility: Clinica Mayo de UMCB
city: Box Hill
country: Australia
facility: Epworth Eastern Hospital
city: Darlinghurst
country: Australia
facility: St Vincent s Hospital Sydney
city: Heidelberg
country: Australia
facility: Austin Health
city: Malvern
country: Australia
facility: Australian Urology Associates Pty Ltd
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
city: St Leonards
country: Australia
facility: Northern Cancer Institute
city: Wahroonga
country: Australia
facility: Australian Clinical Trials - SAN Clinic
city: Westmead
country: Australia
facility: Westmead Hospital
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
city: Goiania
country: Brazil
facility: Associacao de Combate ao Cancer em Goias - Hospital de Cancer Araujo Jorge
city: Ijui
country: Brazil
facility: Oncosite - Centro de Pesquisa Clínica em Oncologia Ltda
city: Natal
country: Brazil
facility: Liga Norte Riograndense Contra O Cancer
city: Porto Alegre
country: Brazil
facility: Irmandade Santa Casa de Misericordia de Porto Alegre
city: Rio de Janeiro
country: Brazil
facility: Universidade do Estado do Rio de Janeiro - UERJ
city: Sao Paulo
country: Brazil
facility: Associacao Umane
city: Sao Paulo
country: Brazil
facility: Fundacao Faculdade de Medicina - Instituto do Cancer do Estado de Sao Paulo
city: Tres Lagoas
country: Brazil
facility: Instituto Do Cancer Brasil
city: Calgary
country: Canada
facility: Prostate Cancer Centre
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver Prostate Centre, Gordon and Leslie Diamond Health Care Centre
state: British Columbia
city: Halifax
country: Canada
facility: Nova Scotia Health Authority
state: Nova Scotia
city: London
country: Canada
facility: London Health Sciences Center
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Center
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre University Health Network
state: Ontario
city: Montreal
country: Canada
facility: CHUM - Centre hospitalier universitaire de Montreal
state: Quebec
city: Quebec
country: Canada
facility: CHU de Quebec Universite Laval Hopital de l Enfant Jesus
city: Hradec Králove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Liberec
country: Czechia
facility: Krajská nemocnice Liberec
city: Olomouc
country: Czechia
facility: Uromedical Center s.r.o.
city: Plzen
country: Czechia
facility: Fakultni nemocnice Plzen, Urologicka klinika
city: Praha 4
country: Czechia
facility: Thomayerova nemocnice
city: Praha
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Angers
country: France
facility: CHU d'Angers
city: Besancon Cedex
country: France
facility: CHRU Besancon Hopital Jean Minjoz
city: Bordeaux N/a
country: France
facility: Hopital Pellegrin CHU Bordeaux
city: Créteil
country: France
facility: APHP - Hopital Henri Mondor
city: Lyon cedex 03
country: France
facility: Hopital Edouard Herriot - CHU Lyon
city: Nantes
country: France
facility: CHU de Nantes hotel Dieu
city: Paris
country: France
facility: Institut Mutualiste Montsouris
city: Quint-Fonsegrives
country: France
facility: Clinique de la Croix du Sud
city: Rennes Cedex
country: France
facility: Chu Rennes Hopital Pontchaillou
city: Toulouse Cedex 9
country: France
facility: CHU de Toulouse - Hôpital Rangueil
city: Tours
country: France
facility: CHRU Tours Hopital Bretonneau
city: Aachen
country: Germany
facility: Universitaetsklinikum der RWTH Aachen
city: Braunschweig
country: Germany
facility: Städtisches Klinikum Braunschweig gGmbH - Standort Salzdahlumer
city: Essen
country: Germany
facility: Universitatsklinikum Essen
city: Frankfurt am Main
country: Germany
facility: Universitatsklinikum Frankfurt
city: Gronau
country: Germany
facility: Prostata zentrum Nordwest
city: Hamburg
country: Germany
facility: Martini-Klinik am Universitätsklinikum Hamburg-Eppendorf Urologie
city: Homburg/Saar
country: Germany
facility: Universitätsklinikum des Saarlandes
city: Koeln
country: Germany
facility: Universitaetsklinikum Koelnt
city: Lubeck
country: Germany
facility: Universitatsklinikum Schleswig Holstein Campus Lubeck
city: Lutherstadt Eisleben
country: Germany
facility: Praxis Dr. med. Ralf Eckert
city: Straubing
country: Germany
facility: Klinikum St. Elisabeth Straubing GmbH
city: Weiden/Opf
country: Germany
facility: Kliniken Nordoberpfalz, Klinik für Urologie
city: Wilhelmshaven
country: Germany
facility: Praxisgemeinschaft f. Onkologie u. Urologie - Germany
city: Beer Yaakov
country: Israel
facility: Asaf Harofe Medical Center
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Kfar Saba
country: Israel
facility: Tel Aviv University Sackler School of Medicine - Meir Medical Center (MMC)
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Abano Terme
country: Italy
facility: Policlinico Abano Terme
city: Acquaviva delle Fonti
country: Italy
facility: Generale Regionale F. Miulli
city: Bassano del Grappa
country: Italy
facility: Ospedale di Bassano del Grappa
city: Brescia
country: Italy
facility: ASST Spedali Civili Brescia
city: Chieti
country: Italy
facility: ASL2 Lanciano - Vasto - Chieti - Ospedale 'SS Annunziata' di Chieti
city: Firenze
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi
city: MIlano
country: Italy
facility: San Raffaele Turro - Istituto di Ricovero e Cura a Carattere Scientifico
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Modena
country: Italy
facility: Clinica di Urologia Policlinico di Modena - Universita di Modena e reggio Emilia
city: Novara
country: Italy
facility: Università del Piemonte Orientale - Ospedale Maggiore della Carità di Novara
city: Orbassano
country: Italy
facility: Universita degli Studi di Torino - Azienda Ospedaliero-Universitaria San Luigi Gonzaga
city: Roma
country: Italy
facility: Universita Campus Bio-Medico di Roma
city: Roma
country: Italy
facility: Istituto Nazionale Tumori Regina Elena
city: Roma
country: Italy
facility: Azienda Ospedaliera Sant Andrea
city: Torino
country: Italy
facility: Ospedale Molinette, AO Città della Salute e della Scienza di
city: Verona
country: Italy
facility: UOC di Urologia AOU Integrata di Verona - Polo Chirurgico Confortini - Ospedale Borgo Trento
city: Akita
country: Japan
facility: Akita University Hospital
city: Chiba
country: Japan
facility: Chiba University Hospital
city: Chuo-ku
country: Japan
facility: Chiba Cancer Center
city: Hakodate
country: Japan
facility: Hakodate Goryoukaku Hospital
city: Hirosaki
country: Japan
facility: Hirosaki University Hospital
city: Kanazawa
country: Japan
facility: Kanazawa University Hospital
city: Kobe
country: Japan
facility: Kobe City Medical Center General Hospital
city: Koshigaya
country: Japan
facility: Dokkyo Medical University Saitama Medical Center
city: Kurume
country: Japan
facility: Kurume University Hospital
city: Kyoto
country: Japan
facility: Kyoto University Hospital
city: Matsuyama
country: Japan
facility: National Hospital Organization Shikoku Cancer Center
city: Minami-Ku
country: Japan
facility: Kitasato University Hospital
city: Miyazaki
country: Japan
facility: University of Miyazaki Hospital
city: Nagano
country: Japan
facility: Nagano Municipal Hospital
city: Osaka City
country: Japan
facility: Osaka International Cancer Institute
city: Osaka Sayama shi
country: Japan
facility: Kindai University Hospital
city: Sakura
country: Japan
facility: Toho University Sakura Medical Center
city: Sapporo-shi
country: Japan
facility: Hokkaido University Hospital
city: Shiwa-gun
country: Japan
facility: Iwate Medical University Hospital
city: Tokyo
country: Japan
facility: Nippon Medical School Hospital
city: Tokyo
country: Japan
facility: Juntendo University Hospital
city: Ube
country: Japan
facility: Yamaguchi University Hospital
city: Yokohama
country: Japan
facility: Yokohama City University Medical Center
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul St Marys Hospital
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek
city: Eindhoven
country: Netherlands
facility: Catharinaziekenhuis
city: Nieuwegein
country: Netherlands
facility: St. Antonius Ziekenhuis (St. Antonius Hospital)
city: Nijmegen
country: Netherlands
facility: Canisius-Wilhelmina Ziekenhuis
city: Bydgoszcz
country: Poland
facility: Samodzielny Publiczny Wielospecjalistyczny Zaklad Opieki Zdrowotnej Mswia W Bydgoszczy
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki NR 1 IM Dr Antoniego Jurasza
city: Koszalin
country: Poland
facility: Szpital Wojewodzki im Mikolaja Kopernika w Koszalinie
city: Krakow
country: Poland
facility: Pratia MCM Krakow
city: Warszawa
country: Poland
facility: City Clinic Sp. z o.o.
city: Wroclaw
country: Poland
facility: Dolnoslaskie Centrum Onkologii, Oddzial Chirurgii Onkologicznej II - Urologia
city: Barnaul
country: Russian Federation
facility: Altai Regional Oncology Dispensary
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Clinical Center Of Oncology And Nuclear Medicine
city: Moscow
country: Russian Federation
facility: Moscow City Clinical Hospital # 62
city: Moscow
country: Russian Federation
facility: Hertzen Oncology Research Institute
city: Omsk
country: Russian Federation
facility: Clinical Oncology Dispensary
city: Tyumen
country: Russian Federation
facility: Medical-sanitary unit 'Neftyanik'
city: Vologda
country: Russian Federation
facility: Vologda Regional Oncological Dispensary
city: A Coruna
country: Spain
facility: Hosp Univ A Coruna
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Cadiz
country: Spain
facility: Hosp. Puerta Del Mar
city: Castellón
country: Spain
facility: Hosp. Gral. Univ. de Castellon
city: Jerez de la Frontera
country: Spain
facility: Hosp. de Jerez de La Frontera
city: Madrid
country: Spain
facility: Hosp. Univ. Ramon Y Cajal
city: Madrid
country: Spain
facility: Hosp. Univ. 12 de Octubre
city: Madrid
country: Spain
facility: Hosp. Univ. La Paz
city: Manacor
country: Spain
facility: Fund. Hosp. de Manacor
city: Málaga
country: Spain
facility: Hosp Virgen de La Victoria
city: Santander
country: Spain
facility: Hosp. Univ. Marques de Valdecilla
city: Sevilla
country: Spain
facility: Hosp. Virgen Del Rocio
city: Valencia
country: Spain
facility: Inst. Valenciano de Oncologia
city: Valencia
country: Spain
facility: Hosp. Clinico Univ. de Valencia
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung Ho Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taichung
country: Taiwan
facility: Tungs' Taichung MetroHarbor Hospital
city: Tainan
country: Taiwan
facility: Chi Mei Medical Center Yong Kang
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital.
city: Bristol
country: United Kingdom
facility: Southmead Hospital
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
city: London
country: United Kingdom
facility: The Royal Marsden NHS Trust
city: London
country: United Kingdom
facility: University College London
city: Preston
country: United Kingdom
facility: Lancashire Teaching Hospitals NHS Foundation Trust Royal Preston Hospital
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
city: Wakefield
country: United Kingdom
facility: Mid Yorkshire NHS Trust
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.