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

Prostatic Neoplasms Clinical Trial

— PROTEUS  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03767244
• Other study ID #: CR108535
• Secondary ID: 56021927PCR30112
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 11, 2019
• Est. completion date: July 19, 2029

Study information

• Verified date: March 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 2517
• Est. completion date: July 19, 2029
• Est. primary completion date: April 22, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Prostatic Neoplasms

Intervention

Drug:
• Apalutamide
Participants will receive apalutamide 240 mg (4 tablets of 60 mg each) orally once daily.
• 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]).
• Placebo
Participants will receive matching placebo oral tablets daily.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Canada,  Czechia,  France,  Germany,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Russian Federation,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Metastasis-Free Survival (MFS)	MFS is defined as the time from randomization to the date of the first 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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Number of Participants with Adverse Events	An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	Up to 30 days after last dose of study drug (Approximately 8 years)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)