A Study of Adding Apalutamide to Radiotherapy and LHRH Agonist in High-Risk Patients With Hormone-Sensitive Prostate Cancer

NCT04557059 | Active Not Recruiting Phase 3 DMC

• 4 other identifiers: CR10870556021927PCR30152019-002957-462023-505852-23-00
• Study Type: interventional
• Target: 693
• Locations: 20 countries
• Sites: 138

Brief Summary

The main purpose of this study is to determine if the addition of apalutamide to radiotherapy (RT) plus luteinizing hormone-releasing hormone agonist (LHRHa) delays metastatic progression as assessed by prostate specific membrane antigen-positron emission tomography (PSMA-PET) or death compared with RT plus LHRHa alone.

Conditions

Prostatic Neoplasms

Outcome Measures

Primary Outcomes (1)

• Prostate specific Membrane Antigen-Positron Emission Tomography (PSMA-PET) Metastatic Progression-free Survival (ppMPFS)

  ppMPFS is defined as the appearance of at least one new PSMA-PET-positive distant lesion compared with the previous scan as assessed by blinded independent central review (BICR) or death.

  Up to 9 years

Secondary Outcomes (7)

• Time to Prostate-Specific Antigen (PSA) Progression

  Up to 9 years

• PSA Response Rate

  Up to 9 years

• PSA Levels at Week 26

  Week 26

• Time to Loco-Regional Progression by PSMA-PET

  Up to 9 years

• Overall Survival

  Up to 9 years

Study Arms (3)

Interventional Cohort (Group 1): RT+ LHRHa

ACTIVE COMPARATOR

Participants will receive radiotherapy (RT) which is defined as prostate-bed plus pelvic lymph node salvage external-beam radiotherapy with or without optional stereotactic body radiation therapy (SBRT), along with a luteinizing hormone-releasing hormone agonist (LHRHa) as a 3-monthly depot preparation within 3 days after randomization and the end of Week 12, or as a 6-monthly depot preparation within 3 days after randomization.

Radiation: Radiotherapy; Drug: LHRHa

Interventional Cohort (Group 2): RT+LHRHa + Apalutamide

EXPERIMENTAL

Participants will receive prostate-bed plus pelvic lymph node salvage external-beam radiotherapy (RT) with or without optional stereotactic body radiation therapy (SBRT), along with a LHRHa as a 3-monthly depot preparation within 3 days after randomization and the end of Week 12, or as a 6-monthly depot preparation within 3 days after randomization. Participants will also receive 240 milligram (mg) of apalutamide starting within 3 days after randomization as film-coated tablets, to be swallowed whole and together once daily with or without food, for a period of 180 Days.

Radiation: Radiotherapy; Drug: LHRHa; Drug: Apalutamide

Observational Cohort(Group3) PSMA-PET Negative Participants

NO INTERVENTION

Enrollment into this cohort will be stopped further. Participants who were PSMA-PET-negative at screening and were already enrolled in the Observational Cohort will continue in this cohort. Data collected in the course of routine clinical practice during this period will include clinical evaluations, disease progression, therapies administered as per standard-of-care at the study-sites and survival status. For Observational Cohort, information will be entered into the electronic case report form (eCRF) from the medical records at least twice a year. The use of any medicinal product(s) for the treatment and management of participants will be at discretion of the treating physician.

Interventions

Radiotherapy RADIATION

Participants will receive radiotherapy (RT) with or without optional stereotactic body radiation therapy (SBRT), which will start within 4 weeks after randomization.

Interventional Cohort (Group 1): RT+ LHRHa; Interventional Cohort (Group 2): RT+LHRHa + Apalutamide

LHRHa DRUG

Participants will be administered with LHRHa (example, leuprolide, goserelin, triptorelin acetate) as a 3-monthly depot preparation within 3 days after randomization and the end of Week 12 or as a 6-monthly depot preparation within 3 days after randomization.

Interventional Cohort (Group 1): RT+ LHRHa; Interventional Cohort (Group 2): RT+LHRHa + Apalutamide

Apalutamide DRUG

Participants will receive therapeutic dose of apalutamide 240 mg once daily for 180 Days.

Also known as: JNJ-56021927

Interventional Cohort (Group 2): RT+LHRHa + Apalutamide

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed adenocarcinoma of the prostate
• Previously treated with radical prostatectomy with or without lymph node dissection and either: a) for biochemical recurrence after radical prostatectomy (RP): any post-operative prostate-specific antigen (PSA) measurement of less than (\<) 0.1 nanogram/milliliter (ng/mL) within 12 months after RP and without any PSA greater than and equal to (\>=) 0.1 ng/mL within the 4 to 8-week period after RP or b) for persistent PSA after RP: PSA \>=0.1 ng/mL within the 4 to 8-week period after RP, confirmed by additional measurement at least 3 weeks later
• Be able to swallow whole the study drug tablets or follow the instructions for admixing with apple sauce
• Results of the Prostate specific membrane antigen-positron emission tomography (PSMA-PET) at screening as determined by blinded independent, central review (BICR), must be: PSMA-PET-negative for any prostate cancer lesions (that is, no loco-regional lesion and no distant lesions); or PSMA-PET-positive for at least one loco-regional (pelvic) lesion without distant extra-pelvic lesion; or PSMA PET- positive for at least one loco--regional (pelvic) lesion with extra-pelvic lesion(s).
• High risk of developing metastasis defined as; a) for biochemical recurrence after RP: pathological Gleason score greater than or equal to (\>=) 8 evaluated from prostate tissue specimen at radical prostatectomy, or prostate-specific antigen doubling time (PSADT) less than or equal to (\<=) 12 months at the time of screening; b) for persistent PSA after RP: pathological Gleason score \>=8, evaluated from prostate tissue specimen at radical prostatectomy
• Participants with evidence of distant metastasis on screening PSMA-PET scan must have no evidence of prostate cancer metastases on screening CT/MRI of the chest/abdomen/pelvis, Technetium 99m \[99mTc\] whole-body bone scan. Participants with a single bone lesion on 99mTc whole-body bone scan should have confirmatory imaging by CT or MRI; if the confirmatory scan confirms the bone lesion, the participant should be excluded from the study. Conventional images (99mTc-bone scan and CT/MRI) from the screening will be evaluated locally before randomization
• Eastern Cooperative Oncology Group Performance Status Grade 0 or 1

You may not qualify if:

• History of pelvic radiation for malignancy
• Previous treatment with androgen deprivation therapy (ADT) for prostate cancer
• Previously treated for biochemical recurrence (BCR) or persistent PSA after RP (previous surgical treatment of one or more loco-regional lesions is allowed)
• Prior treatment with a CYP17 inhibitor (example, oral ketoconazole, orteronel, abiraterone acetate, galeterone) or any androgen receptor (AR) antagonist including bicalutamide, flutamide, nilutamide, apalutamide, enzalutamide or darolutamide and any other medications that may lower androgen levels (estrogens, progestins, aminoglutethimide, etc.), including bilateral orchiectomy
• Known or suspected contraindications or hypersensitivity to apalutamide, Luteinizing Hormone-Releasing Hormone (LHRH) agonist or any of the components of the formulations
• Prior chemotherapy for prostate cancer
• Any evidence of prostate cancer metastasis on computed tomography/magnetic resonance imaging (CT/MRI) of the chest/abdomen/pelvis or 99mTc whole-body bone scan, at any time prior to screening

Sponsors & Collaborators

• Janssen Pharmaceutica N.V., Belgium: lead

Study Sites (141)

Arizona Urology Specialists

Tucson, Arizona, 85741, United States

Location

Arkansas Urology

Little Rock, Arkansas, 72211, United States

Location

Colorado Clinical Research

Lakewood, Colorado, 80228, United States

Location

Urological Research Network

Hialeah, Florida, 33016, United States

Location

First Urology, PSC

Jeffersonville, Indiana, 47130, United States

Location

Michigan Institute of Urology

Troy, Michigan, 48084, United States

Location

Associated Medical Professionals of Ny

Syracuse, New York, 13210, United States

Location

The Urology Group

Cincinnati, Ohio, 45212, United States

Location

Oregon Urology Institute

Springfield, Oregon, 97477, United States

Location

MidLantic Urology

Bala-Cynwyd, Pennsylvania, 19004, United States

Location

Urology Austin

Austin, Texas, 78745, United States

Location

Houston Metro Urology

Houston, Texas, 77027, United States

Location

Spokane Urology

Spokane, Washington, 99202, United States

Location

Bundaberg Hospital

Bundaberg, 4670, Australia

Location

Hervey Bay Hospital

Bundaberg, 4670, Australia

Location

Epworth Healthcare

East Melbourne, 3002, Australia

Location

St Vincent's Hospital - Melbourne

Fitzroy, 3065, Australia

Location

Genesis Care Hurstville

Hurstville, 2220, Australia

Location

Macquarie University Hospital

North Ryde, 2109, Australia

Location

Calvary Mater Newcastle

Waratah, 2298, Australia

Location

GenesisCare Wembley

Wembley, 6014, Australia

Location

Ordensklinikum Linz GmbH Elisabethinen

Linz, 4020, Austria

Location

Universitaetsklinikum Salzburg Landeskrankenhaus

Salzburg, 5020, Austria

Location

Medizinische Universitaet Wien

Vienna, 1090, Austria

Location

ZAS Augustinus

Antwerp, 2610, Belgium

Location

A.Z. Sint Jan

Bruges, 8000, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

Az Groeninge

Kortrijk, 8500, Belgium

Location

Empresa Brasileira de Servicos Hospitalares - EBSERH - Hospital das Clinicas da UFMG

Belo Horizonte, 30130-100, Brazil

Location

Liga Paranaense de Combate ao Cancer

Curitiba, 81520 060, Brazil

Location

Liga Norte Riograndense Contra O Cancer

Natal, 59075-740, Brazil

Location

Associacao Hospitalar Moinhos de Vento

Porto Alegre, 90035-001, Brazil

Location

Irmandade Santa Casa de Misericordia de Porto Alegre

Porto Alegre, 90050-170, Brazil

Location

Oncoclinicas Rio de Janeiro S A

Rio de Janeiro, 22250-905, Brazil

Location

Hospital Sao Rafael

Salvador, 41253 190, Brazil

Location

Sociedade Beneficente de Senhoras Hospital Sirio Libanes

São Paulo, 01308 901, Brazil

Location

Hospital Alemao Oswaldo Cruz

São Paulo, 01421-000, Brazil

Location

Hospital Sao Camilo Unidade Vila Mariana

São Paulo, 04014-002, Brazil

Location

Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein

São Paulo, 05652 900, Brazil

Location

Fakultni nemocnice Plzen, Urologicka klinika

Pilsen, 305 99, Czechia

Location

Urocentrum Praha

Prague, 120 00, Czechia

Location

Urologicka klinika 1 LF UK a VFN

Prague, 120 00, Czechia

Location

Fakultni nemocnice v Motole

Prague, 15006, Czechia

Location

Aalborg University Hospital

Aalborg, 9000, Denmark

Location

Aarhus University Hospital

Aarhus N, 8200, Denmark

Location

Rigshospitalet

Copenhagen N, 2200, Denmark

Location

Gentofte Herlev Hospital

Herlev, 2730, Denmark

Location

Helsinki University Hospital

Helsinki, 00290, Finland

Location

Oulu University Hospital

Oulu, 90220, Finland

Location

Tampere University Hospital

Tampere, 33521, Finland

Location

Turku University Hospital

Turku, 20520, Finland

Location

Vaasa Central Hospital

Vaasa, 65130, Finland

Location

Vivantes Klinikum Am Urban

Berlin, 10967, Germany

Location

Städtisches Klinikum Braunschweig gGmbH - Standort Salzdahlumer

Braunschweig, 38126, Germany

Location

Universitatsklinikum Carl Gustav Carcus Dresden

Dresden, 01307, Germany

Location

Universitatsklinikum Essen

Essen, D-45147, Germany

Location

Klinikum rechts der Isar - der Technischen Universität München

München, 81675, Germany

Location

Universitaetsklinikum Muenster

Münster, 48149, Germany

Location

Péterfy Sándor utcai Kórház

Budapest, 1076, Hungary

Location

Budapesti Bajcsy Zsilinszky Korhaz es Rendelointezet

Budapest, 1106, Hungary

Location

Orszagos Onkologiai Intezet

Budapest, 1122, Hungary

Location

Eszak Budai Szent Janos Centrumkorhaz

Budapest, 1125, Hungary

Location

Budapesti Uzsoki Utcai Korhaz

Budapest, 1145, Hungary

Location

Jahn Ferenc Del-pesti Korhaz es Rendelointezet

Budapest, 1204, Hungary

Location

Debreceni Egyetem Klinikai Kozpont

Debrecen, 4032, Hungary

Location

Radioterapia Oncologica, A.O.U. San'T Orsola

Bologna, 40138, Italy

Location

Azienda Ospedaliero Universitaria Careggi

Florence, 50134, Italy

Location

Ospedale San Raffaele

Milan, 20132, Italy

Location

Fondazione Policlinico Tor Vergata

Roma, 00133, Italy

Location

Istituto Nazionale Tumori Regina Elena

Roma, 00144, Italy

Location

Azienda Ospedaliera Sant Andrea

Roma, 00189, Italy

Location

King Hussein Cancer Center

Amman, 0000, Jordan

Location

St Georges Hospital university medical centre

Beirut, 11 00 2807, Lebanon

Location

American Universitty of Beirut Medical Center

Beirut, 1107 2020, Lebanon

Location

Notre Dame De Secours

Byblos, 3, Lebanon

Location

Centre Hospitalier du Nord

Zghartā, 100, Lebanon

Location

Consultorio de Especialidad en Urologia Privado

Durango, 34000, Mexico

Location

Hospital MAC Leon

León, 37530, Mexico

Location

Avix Investigacion Clinica S C

Monterrey, 64623, Mexico

Location

Oncologia Integral Satelite

Naucalpan, 53100, Mexico

Location

Centro de Investigacion Clinica de Oaxaca

Oaxaca City, 68020, Mexico

Location

Oncocenter

Puebla City, 72530, Mexico

Location

Cuidados Oncologicos

Querétaro, 76000, Mexico

Location

Centrum Onkologii im Prof F Lukaszczyka w Bydgoszczy

Bydgoszcz, 85 796, Poland

Location

NU-MED Grupa S.A Centrum Radioterapii i Onkologii

Elblag, 82-300, Poland

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80 952, Poland

Location

Szpitale Pomorskie Sp z o o

Gdynia, 81 519, Poland

Location

Swietokrzyskie Centrum Onkologii SPZOZ w Kielcach

Kielce, 25 734, Poland

Location

Szpital Wojewodzki im Mikolaja Kopernika w Koszalinie

Koszalin, 75 581, Poland

Location

Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im M Kopernika w Lodzi

Lodz, 93 513, Poland

Location

Radomskie Centrum Onkologii

Radom, 26-600, Poland

Location

Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy

Warsaw, 02 781, Poland

Location

Ipo Lisboa

Lisbon, 1099-023, Portugal

Location

Hosp. Cuf Tejo

Lisbon, 1350-352, Portugal

Location

Fund. Champalimaud

Lisbon, 1400-038, Portugal

Location

Uls Lisboa Ocidental - Hosp. Sao Francisco Xavier

Lisbon, 1449-005, Portugal

Location

Hosp. Da Luz Lisboa

Lisbon, 1500 650, Portugal

Location

Uls Santa Maria - Hosp. Santa Maria

Lisbon, 1649 035, Portugal

Location

Uls Santo Antonio - Hosp. Santo Antonio

Porto, 4099-001, Portugal

Location

Uls de Entre Douro E Vouga - Hosp. Sao Sebastiao

Santa Maria da Feira, 4520-211, Portugal

Location

Ivanovo Regional Oncology Dispensary

Ivanovo, 153040, Russia

Location

City Clinical Hospital #57

Moscow, 105077, Russia

Location

I.M. Sechenov First Moscow State Medical University

Moscow, 119991, Russia

Location

Hertzen Oncology Research Institute

Moscow, 125284, Russia

Location

Leningrad Regional Oncology Dispensary

Saint Petersburg, 191104, Russia

Location

SPb SBIH 'City Clinical Oncological Dispensary'

Saint Petersburg, 197022, Russia

Location

Multifunctional clinical medical center 'Medical city'

Tyumen, 625041, Russia

Location

SHI Sverdlovsk Regional Clinical Hospital #1

Yekaterinburg, 620102, Russia

Location

CUIMED - urologická ambulancia

Bratislava, 851 05, Slovakia

Location

Východoslovenský Onkologický Ústav

Košice, 04191, Slovakia

Location

Univerzitná nemocnica Martin

Martin, 036 59, Slovakia

Location

Uroexam s.r.o.

Nitra, 94901, Slovakia

Location

Urologicka ambulancia e.cho Poprad, s.r.o

Poprad, 05801, Slovakia

Location

MILAB s.r.o.

Prešov, 08001, Slovakia

Location

Privátna urologická ambulancia

Trenčín, 911 01, Slovakia

Location

Hospital Universitario Puerto Del Mar

Cadiz, 11009, Spain

Location

Hosp. Arquitecto Marcide

Ferrol, 15405, Spain

Location

Hosp. de Jerez de La Frontera

Jerez de la Frontera, 11407, Spain

Location

Hosp. Univ. 12 de Octubre

Madrid, 28041, Spain

Location

Hosp. Univ. de La Paz

Madrid, 28046, Spain

Location

Hosp Virgen de La Victoria

Málaga, 29010, Spain

Location

Clinica Univ. de Navarra

Pamplona, 31008, Spain

Location

Hosp. de Navarra

Pamplona, 31008, Spain

Location

Hosp. Virgen Del Rocio

Seville, 41013, Spain

Location

Hosp. Univ. I Politecni La Fe

Valencia, 46026, Spain

Location

Hosp. Clinico Univ. Lozano Blesa

Zaragoza, 50009, Spain

Location

Urologiska Mottagningen

Malmo, 205 02, Sweden

Location

Prostatacancercentrum

Stockholm, 112 19, Sweden

Location

Sodersjukhuset

Stockholm, 11883, Sweden

Location

Adana Baskent Yuregir Hospital

Adana, 01250, Turkey (Türkiye)

Location

Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi

Ankara, 06200, Turkey (Türkiye)

Location

Hacettepe Universitesi Hastanesi

Ankara, 06230, Turkey (Türkiye)

Location

Memorial Ankara Hastanesi

Ankara, 06520, Turkey (Türkiye)

Location

Ankara University Medical Faculty

Ankara, 06590, Turkey (Türkiye)

Location

Koc University, School of Medicine, Koc University Hospital

Istanbul, 34010, Turkey (Türkiye)

Location

Istanbul University Cerrahpasa Medical Faculty

Istanbul, 34096, Turkey (Türkiye)

Location

Bakirkoy Training and Research Hospital

Istanbul, 34147, Turkey (Türkiye)

Location

Goztepe Prof Dr Suleyman Yalcin Sehir Hastanesi

Istanbul, 34722, Turkey (Türkiye)

Location

Kartal Dr Lutfi Kirdar Egitim ve Arastirma Hastanesi

Istanbul, 34890, Turkey (Türkiye)

Location

Dokuz Eylul Universitesi Arastirma ve Uygulama Hastanesi

Izmir, 35340, Turkey (Türkiye)

Location

Sakarya Üniversitesi Tıp Fakültesi Hastanesi

Sakarya, 54187, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Radiotherapy; apalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Janssen Pharmaceutica N.V., Belgium Clinical Trial

  Janssen Pharmaceutica N.V., Belgium

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2020
• First Posted: September 21, 2020
• Study Start: November 12, 2020
• Primary Completion (Estimated): August 27, 2029
• Study Completion (Estimated): August 27, 2029
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

IT (6); DE (6); BR (11); SL (7); ES (11); DK (4); HU (7); LE (4); RU (8); TU (12); PT (8); CZ (4); ME (7); BE (4); AU (8); FI (5); JO (1); SE (3); US (13); PL (9)