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

Primary Purpose

Prostatic Neoplasms

Status

Recruiting

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Apalutamide

Androgen Deprivation Therapy (ADT)

Placebo

About this trial

This is an interventional treatment trial for Prostatic Neoplasms

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

UC San Diego Moores Cancer CenterRecruiting
University of Southern CaliforniaRecruiting
Cedars-Sinai Medical CenterRecruiting
University of California Los AngelesRecruiting
University of California Irvine Medical Center - Chao Family Comprehensive Cancer CenterRecruiting
UC Davis Medical CenterRecruiting
The Urology Center of ColoradoRecruiting
Colorado Clinical ResearchRecruiting
Stamford Hospital
Urology Specialists LLCRecruiting
Mayo Clinic - Division Of Hematology/oncologyRecruiting
Miami Cancer Institute at Baptist Health / Baptist Health Medical GroupRecruiting
Florida HospitalRecruiting
Emory University - Winship Cancer Institute
University of ChicagoRecruiting
Ochsner LSU Health Shreveport - Regional Urology
Dana-Farber Cancer InstituteRecruiting
Beth Isreal Deaconess Medical CenterRecruiting
Michigan Institute of Urology, PCRecruiting
Saint Louis University
Urology Cancer Center, PCRecruiting
Albany Medical CollegeRecruiting
Great Lakes Physician PC d/b/a Western New York Urology AssociatesRecruiting
Memorial Sloan-Kettering Cancer CenterRecruiting
Weill Cornell Medical College
SUNY Upstate Medical UniversityRecruiting
University of North CarolinaRecruiting
Duke University School of Medicine
Medication Management, LLCRecruiting
Carolina Urology Partners, PLLC
Cleveland VA Medical Center
Oklahoma City VAMC
MidLantic UrologyRecruiting
Omega Medical Research
Medical University of South CarolinaRecruiting
Ralph H. Johnson Veterans Affairs Medical CenterRecruiting
Greenville HealthRecruiting
Carolina Urologic Research CenterRecruiting
Vanderbilt University Medical CenterRecruiting
VA North Texas Health Care System
MD Anderson Cancer CenterRecruiting
Virginia Urology
Urology of Virginia, PLCCRecruiting
CAMC Memorial Hospital, Charleston Area Medical Center PhysiciansRecruiting
Hospital AlemanRecruiting
Hospital Italiano de Buenos AiresRecruiting
Cemaic - Centro Privado de Especialidades Medicas Ambulatorias e Investigacion ClinicaRecruiting
Centro Urologico Profesor BengioRecruiting
Uroclinica
Clinica Mayo de UMCB
Epworth Eastern HospitalRecruiting
St. Vincent's Hospital SydneyRecruiting
Austin HealthRecruiting
Australian Urology Associates Pty Ltd
Royal Melbourne HospitalRecruiting
Northern Cancer Institute
Australian Clinical Trials - SAN ClinicRecruiting
Westmead HospitalRecruiting
Princess Alexandra HospitalRecruiting
Associacao de Combate ao Cancer em Goias - Hospital de Cancer Araujo JorgeRecruiting
Oncosite - Centro de Pesquisa Clínica em Oncologia LtdaRecruiting
Liga Norte Riograndense Contra O CancerRecruiting
Irmandade Santa Casa de Misericordia de Porto AlegreRecruiting
Universidade do Estado do Rio de Janeiro - UERJRecruiting
Associacao UmaneRecruiting
Fundacao Faculdade de Medicina - Instituto do Cancer do Estado de Sao Paulo
Instituto Do Cancer BrasilRecruiting
Prostate Cancer CentreRecruiting
Vancouver Prostate Centre, Gordon and Leslie Diamond Health Care CentreRecruiting
Nova Scotia Health AuthorityRecruiting
London Health Sciences CenterRecruiting
Sunnybrook Health Sciences Center
University Health Network (UHN) Princess Margaret Cancer CentreRecruiting
CHUM - Centre hospitalier universitaire de MontrealRecruiting
CHU de Quebec-Universite Laval-Hopital de l'Enfant-JesusRecruiting
Fakultni nemocnice Hradec KraloveRecruiting
Krajská nemocnice LiberecRecruiting
Uromedical Center s.r.o.Recruiting
Fakultni nemocnice Plzen, Urologicka klinikaRecruiting
Thomayerova nemocniceRecruiting
Vseobecna fakultni nemocnice v PrazeRecruiting
CHU d'AngersRecruiting
CHRU Besançon -Hôpital Jean MinjozRecruiting
Hopital Pellegrin CHU BordeauxRecruiting
APHP - Hopital Henri MondorRecruiting
Hopital Edouard Herriot - CHU LyonRecruiting
CHU de Nantes hotel-DieuRecruiting
Institut Mutualiste MontsourisRecruiting
Clinique de la Croix du SudRecruiting
Chu Rennes - Hopital PontchaillouRecruiting
CHU de Toulouse - Hôpital RangueilRecruiting
CHRU Tours Hôpital BretonneauRecruiting
Universitaetsklinikum der RWTH AachenRecruiting
Städtisches Klinikum Braunschweig gGmbH - Standort SalzdahlumerRecruiting
Universitatsklinikum EssenRecruiting
Universitatsklinikum FrankfurtRecruiting
Prostata zentrum NordwestRecruiting
Martini-Klinik am Universitätsklinikum Hamburg-Eppendorf UrologieRecruiting
Universitätsklinikum des SaarlandesRecruiting
Universitaetsklinikum KoelntRecruiting
Universitätsklinikum Schleswig Holstein Campus LübeckRecruiting
Praxis Dr. med. Ralf EckertRecruiting
Klinikum St. Elisabeth Straubing GmbHRecruiting
Kliniken Nordoberpfalz, Klinik für Urologie
Praxisgemeinschaft f. Onkologie u. Urologie - GermanyRecruiting
Asaf Harofe Medical Center
Rambam Health Care CampusRecruiting
Tel Aviv University Sackler School of Medicine - Meir Medical Center (MMC)Recruiting
Rabin Medical Center
The Chaim Sheba Medical CenterRecruiting
Tel Aviv Sourasky Medical CenterRecruiting
Policlinico Abano TermeRecruiting
Generale Regionale F. MiulliRecruiting
Ospedale di Bassano del GrappaRecruiting
ASST Spedali Civili BresciaRecruiting
ASL2 Lanciano - Vasto - Chieti - Ospedale 'SS Annunziata' di ChietiRecruiting
Azienda Ospedaliero Universitaria CareggiRecruiting
San Raffaele Turro - Istituto di Ricovero e Cura a Carattere Scientifico
Ospedale San RaffaeleRecruiting
Istituto Europeo di OncologiaRecruiting
Clinica di Urologia Policlinico di Modena - Università di Modena e reggio EmiliaRecruiting
Università del Piemonte Orientale - Ospedale Maggiore della Carità di NovaraRecruiting
Universita degli Studi di Torino - Azienda Ospedaliero-Universitaria San Luigi GonzagaRecruiting
Universita Campus Bio-Medico di RomaRecruiting
Istituto Nazionale Tumori Regina ElenaRecruiting
Azienda Ospedaliera Sant AndreaRecruiting
Ospedale Molinette, AO Città della Salute e della Scienza diRecruiting
UOC di Urologia AOU Integrata di Verona - Polo Chirurgico Confortini - Ospedale Borgo TrentoRecruiting
Akita University Hospital
Chiba University Hospital
Chiba Cancer Center
Hakodate Goryokaku Hospital
Hirosaki University Hospital
Kanazawa University Hospital
Kobe City Medical Center General Hospital
Dokkyo Medical University Saitama Medical Center
Kurume University Hospital
Kyoto University Hospital
National Hospital Organizaiton Shikoku Cancer Center
Kitasato University Hospital
University of Miyazaki Hospital
Nagano Municipal Hospital
Kindai University Hospital
Osaka International Cancer Institute
Toho University Sakura Medical Center
Hokkaido University Hospital
Iwate Medical University Hospital
Juntendo University Hospital
Nippon Medical School Hospital
Yamaguchi University Hospital
Yokohama City University Medical Center
Chonnam National University HospitalRecruiting
Seoul National University Bundang HospitalRecruiting
Severance Hospital, Yonsei University Health SystemRecruiting
Asan Medical CenterRecruiting
The Catholic University of Korea Seoul St. Mary's HospitalRecruiting
NKI-AVL, AmsterdamRecruiting
CatharinaziekenhuisRecruiting
St. Antonius Ziekenhuis (St. Antonius Hospital)Recruiting
Canisius-Wilhelmina ZiekenhuisRecruiting
Samodzielny Publiczny Wielospecjalistyczny Zakład Opieki Zdrowotnej MSWiA w BydgoszczyRecruiting
Szpital Uniwersytecki NR 1 IM. Dr. Antoniego JuraszaRecruiting
Szpital Wojewódzki im. Mikołaja Kopernika w KoszalinieRecruiting
Pratia MCM KrakowRecruiting
City Clinic Sp. z o.o.Recruiting
Dolnoslaskie Centrum Onkologii, Oddzial Chirurgii Onkologicznej II - UrologiaRecruiting
Altai Regional Oncology DispensaryRecruiting
Chelyabinsk Regional Clinical Center Of Oncology And Nuclear MedicineRecruiting
Moscow City Clinical Hospital # 62Recruiting
Hertzen Oncology Research InstituteRecruiting
Clinical Oncology DispensaryRecruiting
Medical-sanitary unit 'Neftyanik'Recruiting
Vologda Regional Oncological DispensaryRecruiting
Hosp. Univ. A CoruñaRecruiting
Hosp. Univ. Vall D HebronRecruiting
Hosp. Puerta Del MarRecruiting
Hosp. Gral. Univ. De CastellonRecruiting
Hosp. de Jerez de La FronteraRecruiting
Hosp. Univ. Ramon Y CajalRecruiting
Hosp. Univ. 12 de OctubreRecruiting
Hosp. Univ. La PazRecruiting
Fund. Hosp. de ManacorRecruiting
Hosp. Virgen de La VictoriaRecruiting
Hosp. Univ. Marques de ValdecillaRecruiting
Hosp. Virgen Del RocioRecruiting
Inst. Valenciano de OncologiaRecruiting
Hosp. Clinico Univ. de ValenciaRecruiting
Kaohsiung Medical University Chung-Ho Memorial HospitalRecruiting
China Medical University HospitalRecruiting
Taichung Veterans General HospitalRecruiting
Tungs' Taichung MetroHarbor HospitalRecruiting
Chi Mei Medical Center - Yong KangRecruiting
National Taiwan University Hospital.Recruiting
Southmead HospitalRecruiting
University Hospital of Wales
Ninewells Hospital
The Royal Marsden NHS TrustRecruiting
University College LondonRecruiting
Lancashire Teaching Hospitals NHS Foundation Trust Royal Preston HospitalRecruiting
Royal Marsden HospitalRecruiting
MidYorkshire NHS TrustRecruiting
New Cross HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Apalutamide + ADT

Placebo + ADT

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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.

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.

Time to Subsequent First Treatments (TTST-1)

TTST-1 is defined as the time from randomization to the date of first subsequent therapy.

Time to Distant Metastasis (TTDM)

TTDM is defined as the time from the date of enrollment until the first date of distant metastasis.

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.

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.

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.

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.

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.

Number of Participants with Treatment Compliance Rate

Number of participants who are complaint with study treatment will be assessed.

Full Information

NCT ID

NCT03767244

First Posted

December 5, 2018

Last Updated

October 10, 2023

Sponsor

Janssen Research & Development, LLC

1. Study Identification

Unique Protocol Identification Number

NCT03767244

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

June 11, 2019 (Actual)

Primary Completion Date

April 22, 2024 (Anticipated)

Study Completion Date

April 7, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prostatic Neoplasms

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

2500 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Apalutamide + ADT

Arm Type

Experimental

Arm Description

Arm Title

Placebo + ADT

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Apalutamide

Other Intervention Name(s)

JNJ-56021927

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Androgen Deprivation Therapy (ADT)

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Participants will receive matching placebo oral tablets daily.

Primary Outcome Measure Information:

Title

Percentage of Participants with Pathologic complete response (pCR)

Description

pCR is assessed by a pathology blinded independent central radiology review (BICR) as defined in the pathology charter.

Time Frame

Approximately 4 years

Title

Metastasis-Free Survival (MFS)

Description

Time Frame

Up to 7 years and 5 months

Secondary Outcome Measure Information:

Title

Prostate Specific Antigen (PSA)-Free Survival

Description

Time Frame

Approximately 4 years

Title

Event Free Survival (EFS)

Description

Time Frame

Up to 7 years and 5 months

Title

Time to Subsequent First Treatments (TTST-1)

Description

TTST-1 is defined as the time from randomization to the date of first subsequent therapy.

Time Frame

Up to 7 years and 5 months

Title

Time to Distant Metastasis (TTDM)

Description

TTDM is defined as the time from the date of enrollment until the first date of distant metastasis.

Time Frame

Up to 7 years and 5 months

Title

MFS Based on Conventional Imaging

Description

Time Frame

Up to 7 years and 5 months

Title

Number of Participants with Adverse Events

Description

Time Frame