A Study to Compare Darolutamide Given With Androgen Deprivation Therapy (ADT) and Placebo Given With ADT in Men With Hormone Sensitive Prostate Cancer and Raise of Prostate Specific Antigen (PSA) Levels After Local Therapies (ARASTEP)

A Randomized, Double-blind, Placebo-controlled Phase 3 Study of Darolutamide Plus Androgen Deprivation Therapy (ADT) Compared With Placebo Plus ADT in Patients With High-risk Biochemical Recurrence (BCR) of Prostate Cancer

Researchers are looking for a better way to treat men at high-risk of biochemical recurrence (BCR) of prostate cancer.

BCR means that in men who had prostate cancer and were treated by either surgery and/ or radiation therapy, the blood level of a specific protein called PSA rises. PSA is a marker of prostate cancer cells activity. The PSA increase means that the cancer has come back even though conventional imaging such as computed tomography (CT) scans, magnetic resonance imaging (MRI) and bone scans does not show any lesion of prostate cancer. Recently a more sensitive imaging method called prostate-specific membrane antigen [PSMA] positron emission tomography [PET]) /computed tomography [CT]) scan may identify prostate cancer lesions not detectable by conventional imaging. Men with BCR have a higher risk of their cancer spreading to other parts of the body, particularly when PSA levels raised to a certain limit within a short period of time after local therapies. Once the cancer spreads to other parts of the body, it can become even harder to treat.

In men with prostate cancer, male sex hormones (also called androgens) like testosterone can help the cancer grow and spread. To reduce androgens levels in these patients, there are treatments that block androgens production in the body called androgen deprivation therapy (ADT). ADT is often used to stop prostate cancer. Another way to stop prostate cancer growth and spread is to block the action of androgen receptors on prostate cancer cells called androgen receptor inhibitors (ARIs). The new generation ARIs including darolutamide can block the action of androgens receptors and are available for the treatment of prostate cancer in addition to ADT. It is already known that men with prostate cancer benefit from these treatments.

The main objective of this study is to learn if the combination of darolutamide and ADT prolongs the time that the participants live without their cancer getting worse, or to death due to any cause, compared to placebo (which is a treatment that looks like a medicine but does not have any medicine in it) and ADT given for a pre-specified duration of 24 months.

To do this, the study team will measure the time from the date of treatment allocation to the finding of new cancer spread in the participants by using PSMA PET/CT, or death due to any cause. The PSMA PET/CT scans is performed using a radioactive substance called a "tracer" that specifically binds to the prostate-specific membrane antigen (PSMA) which is a protein often found in large amounts on prostate cancer cells.

To avoid bias in treatment, the study participants will be randomly (by chance) allocated to one of two treatment groups. Based on the allocated treatment group, the participants will either take darolutamide plus ADT or placebo plus ADT twice daily as tablets by mouth. The study will consist of a test (screening) phase, a treatment phase and a follow-up phase. The treatment duration is pre-specified to be 24 months unless the cancer gets worse, the participants have medical problems, or they leave the study for any reason. In addition, image guided radiotherapy (IGRT) or surgery is allowed and your doctor will explain the benefits and risks of this type of therapy.

During the study, the study team will:

• take blood and urine samples.
• measure PSA and testosterone levels in the blood samples
• do physical examinations
• check the participants' overall health
• examine heart health using electrocardiogram (ECG)
• check vital signs
• check cancer status using PSMA PET/CT scans, CT, MRI and bone scans
• take tumor samples (if required)
• ask the participants if they have medical problems

About 30 days after the participants have taken their last treatment, the study doctors and their team will check the participants' health and if their cancer worsened. The study team will continue to check this and regularly ask the participants questions about medical problems and subsequent therapies until they leave the study for any reason or until they leave the study for any reason or until the end of the study, whatever comes first.

Study Overview

• Status: Active, not recruiting
• Conditions: Biochemically Recurrent Prostate Cancer
• Intervention / Treatment: Drug: Darolutamide (BAY1841788, Nubeqa); Other: ADT; Other: Placebo matching darolutamide

• Study Type: Interventional
• Enrollment (Actual): 985
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Chris O'Brien Lifehouse
    • Epping, New South Wales, Australia, 3076
      • Northern Hospital
    • Liverpool, New South Wales, Australia, 2170
      • University of New South Wales (UNSW) - Liverpool Hospital - Liverpool Cancer Therapy Centre
    • Wahroonga, New South Wales, Australia, 2076
      • Sydney Adventist Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Eastern Clinical Research Unit - Box Hill
    • East Melbourne, Victoria, Australia, 3002
      • Epworth Healthcare
    • Geelong, Victoria, Australia, 3220
      • Barwon Health
    • Heidelberg, Victoria, Australia, 3084
      • Austin Health
    • Maribyrnong, Victoria, Australia, 3032
      • Western Urology
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital
• Austria
  • State of Vienna
    • Vienna, State of Vienna, Austria, 1090
      • Medizinische Universität Wien- Universitätsklinik für Urologie
    • Vienna, State of Vienna, Austria, 1090
      • Uniklinikum Salzburg - Landeskrankenhaus
  • Styria
    • Salzburg, Styria, Austria, 5020
      • Medizinische Universitaet Graz - Klinische Abteilung für Onkologie - Innere Medizin
  • Tyrol
    • Innsbruck, Tyrol, Austria, 6020
      • Medizinische Universität Innsbruck
  • Upper Austria
    • Linz, Upper Austria, Austria, 4020
      • Ordensklinikum Linz GmbH Elisabethinen
    • Vienna, Upper Austria, Austria, 4020
      • Krankenhaus der Barmherzigen Brüder
• Belgium
  • Ghent, Belgium, 9000
    • Maria Middelares General Hospital | Medical Oncology Department
  • Ghent, Belgium, 9000
    • UZ Gent - department Urology
  • Hasselt, Belgium, 3500
    • Jessa Hospital | Campus Virga Jesse - Data Management Oncology and Hematology Department
  • Kortrijk, Belgium, 8500
    • AZ Groeninge Campus Kennedylaan - Urology
  • La Louvière, Belgium, 7100
    • Hopital de La Louvière - Site Jolimont - Oncology department
  • Leuven, Belgium, 3000
    • Universitair Ziekenhuis Leuven | Gasthuisberg Campus - Urology Department
• Brazil
  • Rio de Janeiro, Brazil, 20551-030
    • Universidade Estadual do Rio de Janeiro
  • Rio de Janeiro, Brazil, 22281-100
    • Instituto D'Or Pesquisa e Ensino (IDOR) (D'Or Institute for Research & Education) - Rio de Janeiro
  • Ceará
    • Fortaleza, Ceará, Brazil, 60135-237
      • Oncocentro - Fortaleza
  • Estado de Bahia
    • Salvador, Estado de Bahia, Brazil, 41950-640
      • Assistência Multidisciplinar em Oncologia (AMO)
  • Minas Gerais
    • Uberlândia, Minas Gerais, Brazil, 90035-001
      • Hospital Moinhos de Vento-Centro Clínico
  • Paraná
    • Curitiba, Paraná, Brazil, 81520-060
      • Liga Paranaense de Combate ao Cancer-Hosp Erasto Gaertner
  • Rio Grande do Norte
    • Natal, Rio Grande do Norte, Brazil, 59040-000
      • Liga Norte Riograndense Contra o Cancer | Centro de Pesquisa Clínica
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90850-170
      • Hospital Mae de Deus
  • São Paulo
    • Santo André, São Paulo, Brazil, 09060-650
      • Faculdade de Medicina do ABC
    • São Paulo, São Paulo, Brazil, 01327-001
      • Hospital Alemao Oswaldo Cruz
    • São Paulo, São Paulo, Brazil, 01246-000
      • Instituto do Cancer do Estado de Sao Paulo
    • São Paulo, São Paulo, Brazil, 01323-001
      • Real e Benemerita Associacao Portuguesa de Beneficencia
    • São Paulo, São Paulo, Brazil, 04039-004
      • Inst. de Assistência Médica ao Sérvidor Público Estadual
    • São Paulo, São Paulo, Brazil, 13083-888
      • Hospital das Clínicas da Universidade de Campinas - UNICAMP
    • São Paulo, São Paulo, Brazil, 01308-050
      • Hospital Sírio Libanês
    • São Paulo, São Paulo, Brazil, 01525-001
      • Hospital do Cancer de Sao Paulo - A. C. Camargo
    • São Paulo, São Paulo, Brazil, 41253-190
      • Hospital Sao Rafael
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2V 1P9
      • Prostate Cancer Centre
    • Edmonton, Alberta, Canada, T6G 1Z1
      • Kaye Edmonton Clinic | Dianne and Irving Kipnes Urology Centre
  • British Columbia
    • Abbotsford British Columbia, British Columbia, Canada, V2S 0C2
      • BC Cancer | Abbotsford
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver Prostate Centre
    • Victoria, British Columbia, Canada, V8R 6V5
      • BC Cancer | Victoria
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Queen Elizabeth II Health Sciences Centre | Oncology
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • St Joseph's Healthcare Hamilton | Cardiology
    • London, Ontario, Canada, N6A 4L6
      • Victoria Hospital | Oncology
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre - Oncology Department
  • Province
    • Québec, Province, Canada, G6V 3Z1
      • L'Hôtel-Dieu de Lévis | Urology
  • Quebec
    • Gatineau, Quebec, Canada, J8P 7H2
      • Hopital de Gatineau | Oncology
    • Greenfield Park, Quebec, Canada, J4V 2H3
      • Urology South Shore Research - Research Department
    • Montreal, Quebec, Canada, H1T 2M4
      • Hôpital Maisonneuve-Rosemont | Oncology
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital | Radiation Oncology
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre hospitalier universitaire de Sherbrooke (CHUS) | Oncology
    • Trois-Rivières, Quebec, Canada, G8Z 3R9
      • Hôpital du Centre-de-la-Mauricie | Radio-oncologie
• China
  • Beijing, China, 100730
    • Peking Union Medical College Hospital (PUMCH) - East Location
  • Nanjing, China, 210029
    • Jiangsu Provincial People's Hospital - The First Affiliated Hospital of Nanjing Medical University
  • Tianjin, China, 300308
    • Tianjin Cancer Hospital, Airport Hospital
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100034
      • Peking University First Hospital - Oncology Department
  • Hubei
    • Wuhan, Hubei, China, 430071
      • Zhongnan hospital ,Wuhan University
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital - Oncology Department
  • Jiangsu
    • Nanjing, Jiangsu, China, 210006
      • Nanjing First Hospital
    • Shanghai, Jiangsu, China, 200000
      • Fudan University Shanghai Cancer Center - Oncology Department
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital,Sichuan University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The 1st Affiliated Hospital of Zhejiang University
• Czechia
  • Brno, Czechia, 602 00
    • Masarykova Univerzita - Masarykuv Onkologicky Ustav (MOU) - Klinika Komplexni Onkologicke Pece (KKOP)
  • Brno, Czechia, 602 00
    • Fakultni nemocnice u Sv. Anny, Onkologicko-chirurgicke oddeleni
  • Olomouc, Czechia, 779 00
    • Fakultní nemocnice Olomouc - Onkologická klinika
  • Prague, Czechia, 128 08
    • Všeobecná fakultní nemocnice v Praze - Urologická klinika
  • Prague, Czechia, 140 59
    • Thomayerova Nemocnice (TN) (Thomayers Hospital) - Onkologicka Klinika 1. LF UK A TN
  • Prague, Czechia, 15006
    • Fakultní nemocnice Motol a Homolka, Pracovište MOTOL - Onkologická klinika 2. LF UK a FNMH
• Denmark
  • København Ø, Denmark, 2100
    • Rigshospitalet - Kræftbehandling
  • Central Jutland
    • Aarhus N, Central Jutland, Denmark, 8200
      • Aarhus Universitetshospital
  • North Denmark
    • Aalborg, North Denmark, Denmark, 9000
      • Aalborg University Hospital
  • Region Sjælland
    • Næstved, Region Sjælland, Denmark, 4700
      • Sjællands University hospital Næstved
• Finland
  • North Ostrobothnia
    • Oulu, North Ostrobothnia, Finland, 90220
      • Oulu University Hospital, Oulun yliopistollinen sairaala (OYS)
  • Pirkanmaa
    • Tampere, Pirkanmaa, Finland, 33520
      • Tampere University Hospital, Tampereen yliopistollinen sairaala (TAYS)
  • Southwest Finland
    • Turku, Southwest Finland, Finland, 20540
      • Turku University Hospital, Turun yliopistollinen sairaala (TYKS) - Urologia
  • Uusimaa
    • Helsinki, Uusimaa, Finland, 00029
      • HUS-Yhtymä, Helsingin yliopistollinen sairaala (HUS) - Urologia
• France
  • Auvergne-Rhône-Alpes
    • Clermont-Ferrand, Auvergne-Rhône-Alpes, France, 63000
      • Centre Hospitalier Universitaire de Clermont Ferrand - Gabriel Montpied - Service Urologie
    • La Tronche, Auvergne-Rhône-Alpes, France, 38700
      • Center Hospitalier Michallon - Grenoble - Service d Urologie et de la transplantation Renale
    • Lyon, Auvergne-Rhône-Alpes, France, 69373
      • UNICANCER - Centre Leon-Berard (CLB) - Medical oncology
    • Pierre-Bénite, Auvergne-Rhône-Alpes, France, 69495
      • HCL - Centre Hospitalier Lyon Sud
  • Bourgogne-Franche-Comté
    • Besançon, Bourgogne-Franche-Comté, France, 25000
      • CHRU Besancon - Hopital Jean Minjoz
    • Dijon, Bourgogne-Franche-Comté, France, 21000
      • Institut de cancerologie de Bourgogne - Departement radiotherapie
    • Dijon, Bourgogne-Franche-Comté, France, 21079
      • Centre Georges Francois Leclerc Dijon - service de radiotherapie
  • Brittany Region
    • Brest, Brittany Region, France, 29200
      • Hopital La Cavale Blanche - CHU de Brest - institut de cancerologie et d'imagerie
    • Rennes, Brittany Region, France, 35000
      • CHU Rennes - Hopital Pontchaillou - Urologie
  • Grand Est
    • Reims, Grand Est, France, 51056
      • Institut de Cancerologie Jean Godinot - Departement oncologie medicale
    • Strasbourg, Grand Est, France, 67033
      • ICANS - Institut de Cancerologie de Strasbourg Europe
    • Vandœuvre-lès-Nancy, Grand Est, France, 54519
      • Institut de Cancérologie de Lorraine - Alexis Vautrin
  • Hauts-de-France
    • Lille, Hauts-de-France, France, 59000
      • Hopital Claude Huriez - Lille - Urologie
    • Lille, Hauts-de-France, France, 59000
      • Hopital Prive Le Bois - Centre Bourgogne - Service radiotherapie oncologie
  • New Aquitaine
    • Bayonne, New Aquitaine, France, 64100
      • Centre d' Oncologie du Pays Basque Clinique Belharra - Bayonne - Oncologie medicale
    • Bordeaux, New Aquitaine, France, 33000
      • CHU Bordeaux - Hopital Pellegrin - Service urologie
  • Occitanie
    • Montpellier, Occitanie, France, 34070
      • Clinique Clémentville
    • Toulouse, Occitanie, France, 31100
      • Institut Claudius Regaud - iUCT Oncopole - Service oncologie
  • Pays de la Loire Region
    • Saint-Herblain, Pays de la Loire Region, France, 44800
      • Institut de Cancerologie de l'Ouest - Saint Herblain - Unite de therapie precoce
  • Île-de-France Region
    • Créteil, Île-de-France Region, France, 94000
      • APHP - Hopital Henri Mondor - Departement Urologie
    • Saint-Cloud, Île-de-France Region, France, 92210
      • Institut Curie - Saint-Cloud
    • Villejuif, Île-de-France Region, France, 94800
      • Gustave Roussy - Departement Oncologie-Radiotherapie
• Germany
  • Aachen, Germany, 52074
    • Universitätsklinikum Aachen / Klinik und Poliklinik für Urologie und Kinderurologie
  • Bergisch Gladbach, Germany, 51465
    • Marien-Krankenhaus Bergisch Gladbach
  • Berlin, Germany, 10967
    • Vivantes Klinikum am Urban
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg-Eppendorf - Martini-Klinik am UKE GmbH
  • Jena, Germany, 7747
    • Universitaetsklinikum Jena - Klinik fuer Urologie
  • Kiel, Germany, 24105
    • Universitätsklinikum Schleswig-Holstein/ Klinik für Urologie
  • Mainz, Germany, 55131
    • Johannes Gutenberg-Universität Mainz - Urologie
  • Stuttgart, Germany, 70174
    • Klinikum Stuttgart / Klinik für Urologie und Transplantationschirurgie
  • Wesel, Germany, 46483
    • Urologische Gemeinschaftspraxis Wesel
  • Baden-Wurttemberg
    • Mannheim, Baden-Wurttemberg, Germany, 68135
      • Klinikum Mannheim GmbH
    • Nürtingen, Baden-Wurttemberg, Germany, 72622
      • Studienpraxis Urologie
  • Bavaria
    • Würzburg, Bavaria, Germany, 97080
      • Universitatsklinikum Wurzburg
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 60590
      • Universitätsklinikum der Johann Wolfgang Goethe Universität
  • Lower Saxony
    • Braunschweig, Lower Saxony, Germany, 38126
      • Städtisches Klinikum Braunschweig GmbH
    • Göttingen, Lower Saxony, Germany, 37075
      • Universitätsmedizin der Georg-August-Universität Göttingen
  • North Rhine-Westphalia
    • Duisburg, North Rhine-Westphalia, Germany, 47169
      • Urologicum Duisburg
    • Herne, North Rhine-Westphalia, Germany, 44625
      • Marienhospital Herne Universitätsklinik
    • Münster, North Rhine-Westphalia, Germany, 48149
      • Universitatsklinikum Munster
  • Saxony
    • Dresden, Saxony, Germany, 1307
      • Universitatsklinikum Carl Gustav Carus An Der Technischen Universitat Dresden
  • Saxony-Anhalt
    • Magdeburg, Saxony-Anhalt, Germany, 39120
      • Medizinische Fakultät der Otto-von-Guericke Universität
• Hungary
  • Budapest, Hungary, 1122
    • Orszagos Onkologiai Intezet
  • Budapest, Hungary, 1145
    • Budapesti Uzsoki Utcai Korhaz
  • Budapest, Hungary, 1204
    • Budapesti Jahn Ferenc Del-pesti Korhaz es Rendelointezet
  • Budapest, Hungary, 1082
    • Semmelweis Egyetem, Altalanos Orvostudomanyi Kar, Urologiai Klinika
  • Győr, Hungary, 9024
    • Gyor-Moson-Sopron Vármegyei Petz Aladár Oktató Kórház
  • Nyíregyháza, Hungary, 4400
    • Szabolcs-Szatmár-Bereg Vármegyei Oktatókórház Nyíregyházi Jósa András Tagkórház
• Italy
  • Bergamo, Italy, 24125
    • Cliniche Gavazzeni S.p.A - Dipartimento Area Chirurgia Unità Operativa di Urologia
  • Cuneo, Italy, 12100
    • Azienda Ospedaliera Santa Croce e Carle - Oncologia
  • Apulia
    • Foggia, Apulia, Italy, 71122
      • Azienda Ospedaliero Universitaria Ospedali Riuniti_Foggia - Oncologia Medica e Terapia Biomolecolare Universitaria
  • Campania
    • Naples, Campania, Italy, 80131
      • IRCCS Istituto Nazionale Tumori Fondazione Pascale - S. C. Oncologia Clinica Sperimentale Uro-Ginecologica
  • Emilia-Romagma
    • Bologna, Emilia-Romagma, Italy, 40139
      • Azienda Unita Sanitaria Locale Di Bologna_Ospedale Bellaria - Oncologia Medica
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • Azienda Ospedaliero-Universitaria Di Bologna IRCCS_Policlinico Sant'Orsola - Urologia
    • Modena, Emilia-Romagna, Italy, 41124
      • Azienda Ospedaliero Universitaria di Modena_Policlinico - Oncologia
    • Reggio Emilia, Emilia-Romagna, Italy, 42123
      • Azienda USL IRCCS di Reggio Emilia_Arcispedale Santa Maria Nuova - S.C. Oncologia Provinciale
  • Friuli Venezia Giulia
    • Aviano, Friuli Venezia Giulia, Italy, 33081
      • Centro di Riferimento Oncologico di Aviano - Oncologia Radioterapica
  • Lazio
    • Rome, Lazio, Italy, 00128
      • I.F.O. Istituti Fisioterapici Ospitalieri_Ospedale Regina Elena - Urologia
    • Rome, Lazio, Italy, 00168
      • Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Degenza di Radioterapia Oncologica
  • Liguria
    • Genoa, Liguria, Italy, 16132
      • IRCCS Ospedale Policlinico San Martino - Oncologia Medica 1
  • Lombardy
    • Bergamo, Lombardy, Italy, 24127
      • Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII - Oncologia
    • Milan, Lombardy, Italy, 20132
      • Ospedale San Raffaele s.r.l - Urologia
    • Rozzano, Lombardy, Italy, 20089
      • Humanitas Mirasole S.p.A. - Oncologia Medica ed Ematologia
  • Piedmont
    • Turin, Piedmont, Italy, 10126
      • A.O.U. Città della Salute e della Scienza di Torino_Molinette - Urologia U
  • Trentino-Alto Adige
    • Trento, Trentino-Alto Adige, Italy, 38122
      • Azienda Provinciale Per I Servizi Sanitari_Ospedale Santa Chiara - UO Oncologia Medica
  • Umbria
    • Perugia, Umbria, Italy, 06129
      • A.O. di Perugia_Hospital Santa Maria della Misericordia - S.C. Radioterapia Oncologica
  • Veneto
    • Castelfranco Veneto, Veneto, Italy, 31033
      • Istituto Oncologico Veneto_Castelfranco Veneto - UOC Urologia Oncologica
    • Roma, Veneto, Italy, 00133
      • Azienda Ospedaliera Policlinico Universitario Tor Vergata - UOC Radioterapia
• Japan
  • Kyoto, Japan, 606-8507
    • Kyoto University Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital
  • Ishikawa-ken
    • Kanazawa, Ishikawa-ken, Japan, 920-8641
      • Kanazawa University Hospital
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 236-0004
      • Yokohama City University Hospital
  • Osaka
    • Suita, Osaka, Japan, 565-0871
      • The University of Osaka Hospital
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8519
      • Institute of Science Tokyo Hospital
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • University Medical Center Groningen | Urology Department
  • North Holland
    • Hilversum, North Holland, Netherlands, 1213 VG
      • Tergooi MC | Hilversum - Wetenschapsbureau
  • South Holland
    • Dordrecht, South Holland, Netherlands, 3300 AK
      • Albert Schweitzer Hospital | Internal Medicine - Oncology Department
    • Rotterdam, South Holland, Netherlands, 3045 PM
      • St. Franciscus Gasthuis
    • The Hague, South Holland, Netherlands, 2545 AA
      • HagaZiekenhuis van Den Haag
  • Utrecht
    • Nieuwegein, Utrecht, Netherlands, 3435 CM
      • St. Antonius Ziekenhuis | Utrecht - R&D Interne Geneeskunde
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital
  • Bay of Plenty
    • Tauranga, Bay of Plenty, New Zealand, 3112
      • Tauranga Urology Research Limited
  • Canterbury
    • Christchurch, Canterbury, New Zealand, 8013
      • Canterbury Urology Research Trust
  • Manawatu-Wanganui
    • Palmerston North, Manawatu-Wanganui, New Zealand, 4442
      • MidCentral District Health Board (MDHB) - Palmerston North Hospital (PNH)
• Poland
  • Bydgoszcz, Poland, 85-796
    • Centrum Onkologii im. Prof. Franciszka Lukaszczyka
  • Kielce, Poland, 25-734
    • Swietokrzyskie Centrum Onkologii
  • Krakow, Poland, 31-864
    • Centrum Medyczne iMed24
  • Lublin, Poland, 20-582
    • Medrise Sp. z o.o. Centrum Badan Klinicznych
  • Warsaw, Poland, 04-073
    • Szpital Grochowski im. dr.med. Rafala Masztaka
  • Wroclaw, Poland, 54-239
    • EMC Instytut Medyczny SA - Penta Hospitals Przychodnie, Wroclaw Wejherowska
• Portugal
  • Coimbra, Portugal, 3004-561
    • Unidade Local de Saúde de Coimbra, E.P.E. - Hospitais da Universidade de Coimbra - Serviço de Urologia
  • Lisbon, Portugal, 1500-650
    • Luz Saude | Hospital da Luz Lisboa - Centro de Investigacao Clinica
  • Lisbon, Portugal, 1350-352
    • Companhia Uniao Fabril | Hospital CUF Tejo - Academic Center - Research Center
  • Lisbon, Portugal, 1649-035
    • Hospital Santa Maria | Centro de Investigacao Clinica
  • Lisbon, Portugal, 1099-023
    • Instituto Portugues de Oncologia de Lisboa | Unidade de Investigacao Clinica - Departamento de Urologia
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar I Urologia
  • Barcelona, Spain, 08025
    • Fundacio Puigvert | Urologia
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall D Hebron | Oncologia Radioterapica
  • Barcelona, Spain, 8036
    • Hospital Clinic De Barcelona | Urologia
  • Cadiz, Spain, 11009
    • Hospital Universitario Puerta Del Mar | Urologia
  • Madrid, Spain, 28050
    • Hospital Universitario Hm Sanchinarro | Oncologia
  • Madrid, Spain, 28033
    • MD Anderson Cancer Center | Oncologia Radioterapica
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon Y Cajal | Oncologia Radioterapica
  • Murcia, Spain, 30008
    • Hospital General Universitario Morales Meseguer | Urologia
  • Málaga, Spain, 20910
    • Hospital Universitario Virgen De La Victoria | Urologia
  • Seville, Spain, 41013
    • Hospital Universitario Virgen Del Rocio S.L. | Urologia
  • Valencia, Spain, 46009
    • Fundacion Instituto Valenciano De Oncologia | Urologia
  • Valencia, Spain, 46009
    • Hospital Universitario Y Politecnico La Fe | Oncologia Radioterapica
  • A Coruña
    • Santiago de Compostela, A Coruña, Spain, 15706
      • Complexo Hospitalario Universitario De Santiago | Oncologia Radioterapica
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marques De Valdecilla - Urologia
• Sweden
  • Skåne County
    • Malmö, Skåne County, Sweden, 214 28
      • Skånes Universitetssjukhus - Malmö - Urologi
  • Västra Götaland County
    • Gothenburg, Västra Götaland County, Sweden, 413 45
      • Sahlgrenska Universitetssjukhuset - Sahlgrenska Sjukhuset - Urologi
• Taiwan
  • Taichung, Taiwan, 435403
    • Tungs' Taichung MetroHarbor Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei, Taiwan, 112019
    • Koo Foundation Sun Yet-Sen Cancer Centre
  • Taoyuan, Taiwan, 33305
    • Chang Gung Memorial Hospital at Linkou
• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, NW1 2PG
      • University College London Hospitals NHS Foundation Trust | University College Hospital (UCLH) - Cancer Clinical Trials Unit
    • London, Greater London, United Kingdom, SW3 6JJ
      • The Royal Marsden NHS Foundation Trust | The Royal Marsden Hospital - The Royal Marsden Clinical Trials Unit (CTU)
    • London, Greater London, United Kingdom, W68RF
      • Imperial College Healthcare NHS Trust | Charing Cross Hospital - Cancer Services
  • Middlesex
    • Northwood, Middlesex, United Kingdom, HA6 2RN
      • East and North Hertfordshire NHS Trust - Mount Vernon Hospital - Mount Vernon Cancer Centre (MVCC)
  • Surrey
    • Guildford, Surrey, United Kingdom, GU2 7XX
      • Royal Surrey NHS Foundation Trust | Royal Surrey County Hospital - Cancer Centre
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Hospital - Phoenix - Cardiology
  • California
    • Duarte, California, United States, 91010
      • City of Hope - Duarte Cancer Center
    • Los Angeles, California, United States, 90033
      • USC Norris Comprehensive Cancer Center
    • Los Angeles, California, United States, 90048
      • Tower Urology
    • Los Angeles, California, United States, 90095
      • UCLA Clark Urology Center
    • San Francisco, California, United States, 94143
      • UCSF Bakar Precision Cancer Medicine Building - Genitourinary
  • Colorado
    • Lakewood, Colorado, United States, 80228
      • Colorado Urology - St. Anthony Hospital Campus
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Medicine - Urology
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • The University of Kansas Cancer Center - Richard and Annette Bloch Radiation Oncology Pavilion
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Chesapeake Urology Associates - Towson
    • Baltimore, Maryland, United States, 21231
      • Sidney Kimmel Comprehensive Cancer Center - Johns Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute - Oncology Department
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute - Detroit Headquarters
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • M Health Fairview Masonic Cancer Clinic - Clinics and Surgery Center
  • Missouri
    • St Louis, Missouri, United States, 63110-1032
      • Washington University School of Medicine - Center for Advanced Medicine (CAM)
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • XCancer Omaha
  • New York
    • Mineola, New York, United States, 11501
      • NYU Langone Health
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai - Oncology
  • North Carolina
    • Greensboro, North Carolina, United States, 27403
      • Alliance Urology Specialists
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29579
      • Carolina Urological Research Center
  • Texas
    • Dallas, Texas, United States, 75235
      • University Hospital Simmons Cancer Center Genitourinary Clinic
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center - Texas Medical Center
    • San Antonio, Texas, United States, 78240
      • The Urology Place
    • San Antonio, Texas, United States, 78229
      • USA Clinical Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Capable of giving signed informed consent as described which includes compliance with the requirements, restrictions listed in the informed consent form (ICF), and in this protocol.
• Male ≥18 years of age at the time of signing the informed consent.
• Histologically or cytologically confirmed adenocarcinoma of prostate.
• Prostate cancer initially treated by: radical prostatectomy (RP) followed by adjuvant radiotherapy (ART), or salvage radiotherapy (SRT), or RP in participants who are unfit for (or refused) ART or SRT, or primary radiotherapy (RT).
• High-risk biochemical recurrence (BCR), defined as Prostate-specific antigen doubling time (PSADT) <12 months calculated using the formula provided by the Sponsor, and PSA ≥0.2 ng/mL after ART or SRT post RP or after RP in participants who are unfit for ART or SRT (local or central values accepted), or PSA ≥2 ng/mL above the nadir after primary RT only (local or central values accepted).
• Participants must undergo prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) within the 42-day Screening period using either 18F-DCFPyL (piflufolastat F 18) or 68Ga-PSMA-11 which will be assessed by blinded independent central review (BICR) to identify at least one PSMA PET/CT lesion of prostate cancer.
• Serum testosterone ≥150 ng/dL (5.2 nmol/L) (local assessment is allowed whenever central assessment cannot be done).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Blood counts at screening: Hemoglobin ≥9.0 g/dL (participant must not have received blood transfusion within 7 days prior to sample being taken); Absolute neutrophil count (ANC) ≥1.5x10^9/L (participant must not have received any growth factor within 4 weeks prior to sample being taken); Platelet count ≥100x10^9/L.
• Screening values of: Alanine aminotransferase (ALT) ≤1.5 x upper limit of normal (ULN); Aspartate aminotransferase (AST) ≤1.5 x ULN; Total bilirubin (TBL) ≤1.5 ULN, (except participants with a diagnosis of Gilbert's disease); Estimated glomerular filtration rate (eGFR) >40 ml/min/1.73 m^2 calculated by the CKD-EPI formula.
• Sexually active male participants must agree to use contraception as detailed in the protocol during the Treatment period and for at least 1 week after the last dose of study treatment, and refrain from donating sperm during this period.

Exclusion Criteria:

• Pathological finding consistent with small cell, ductal or ≥50 % component of neuroendocrine carcinoma of the prostate.
• History of bilateral orchiectomy.
• Metastases or recurrent /new malignant lesions in prostate gland/bed seminal vesicles, lymph nodes below the CIA bifurcation on conventional imaging (CI) as assessed by BICR during screening.
• Brain metastasis on PSMA PET /CT by BICR at screening.
• High-risk BCR after primary radiotherapy with new loco-regional lesions on screening PSMA PET/CT who are eligible for curative salvage prostatectomy.

Note: Participants treated with curative salvage prostatectomy after primary RT who meet the PSA criteria (inclusion criteria 5) may be considered for the study.

• Prior treatment with second generation (e.g. enzalutamide, apalutamide) androgen receptor inhibitors (ARIs) and CYP 17 inhibitors (e.g., abiraterone) within 18 months prior to signing of the ICF.
• Prior treatments with PSMA-radiotherapeutics within 12 months prior to randomization.
• Prior radiotherapy (including image-guided radiotherapy) as primary, adjuvant or salvage treatment completed within 8 weeks prior to signing of the ICF.
• Any prior malignancy (other than adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently in complete remission) within 5 years.
• History of pelvic radiotherapy for other malignancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Darolutamide+ADT; Participants will receive darolutamide plus ADT twice daily with food for a pre-specified duration of 24 months.	Drug: Darolutamide (BAY1841788, Nubeqa); Coated tablet, 300 mg / tablet, oral.; Other: ADT; Luteinizing hormone-releasing hormone [LHRH] agonist/antagonists
Placebo Comparator: Placebo+ADT; Participants will receive Placebo plus ADT twice daily with food for a pre-specified duration of 24 months.	Other: ADT; Luteinizing hormone-releasing hormone [LHRH] agonist/antagonists; Other: Placebo matching darolutamide; Coated tablet, oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Radiological progression-free survival (rPFS) by Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) assessed by Blinded independent central review (BICR)	After randomization to after last treatment, approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metastasis-free survival (MFS) by Conventional imaging (CI) assessed by BICR		After randomization to after last treatment, approximately 46 months
Time to initiation of first subsequent systemic antineoplastic therapy		After randomization to after last treatment, approximately 46 months
Time to loco-regional progression by PSMA PET/CT		After randomization to after last treatment, approximately 46 months
Time to first Symptomatic skeletal event (SSE)		After randomization to after last treatment, approximately 46 months
Overall survival (OS)		After randomization to after last treatment, approximately 46 months
Prostate-specific antigen (PSA) undetectable rates (<0.2 ng/mL)		After randomization to after last treatment, approximately 46 months
Time to deterioration in the Functional Assessment of Cancer Therapy-Prostate (FACT-P) total score	FACT-P is a multidimension, selfreport QoL instrument specifically designed for patients with prostate cancer. It consists of 39 questions items, made up by 2 parts: the 27 questions for functional assessment of cancer therapy general (FACT-G) and 12 prostate cancer subscale questions. It assesses 4 main domains which are: physical (n=7), social/family (n=7), emotional (n=6) and functional wellbeing (n=7).	After randomization to after last treatment, approximately 24 months
Number of participants with Treatment-emergent adverse events (TEAEs) and Treatment-emergent serious adverse events (TESAEs) categorized by severity		After the first treatment until 30 days (+7 days) after the last treatment, up to 25 months
Number of participants who discontinue study treatment due to a TEAE		After the first treatment until 30 days (+7 days) after the last treatment, up to 25 months
Time to symptomatic progression		After randomization to after last treatment, approximately 46 months
Time to Castration-resistant prostate cancer (CRPC)		After randomization to after last treatment, approximately 46 months

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• Morgans AK, Chehrazi-Raffle A, Niazi T, Shore ND, Ross AE, Roder A, Gomes AJ, Supiot S, Barthelemy P, Hatano K, Ruiz CBC, Yoshida S, Herrera-Imbroda B, Gratton M, Gschwend JE, Hope TA, Joensuu H, Kuss I, Le Berre MA, Dimova-Dobreva M, Fizazi K. Darolutamide plus androgen-deprivation therapy in high-risk biochemical recurrence of prostate cancer (ARASTEP). Future Oncol. 2025 Nov;21(27):3491-3498. doi: 10.1080/14796694.2025.2577633. Epub 2025 Nov 11.

Helpful Links

• Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2023
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): March 29, 2030

Study Registration Dates

• First Submitted: March 21, 2023
• First Submitted That Met QC Criteria: March 21, 2023
• First Posted (Actual): April 3, 2023

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: darolutamide; high risk BCR; PSMA PET imaging
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; darolutamide
• Other Study ID Numbers: 21492; 2022-501343-33-00 (Registry Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No