A Study to Compare Darolutamide Given With Androgen Deprivation Therapy (ADT) With ADT in Men With Hormone Sensitive Prostate Cancer and Raise of Prostate Specific Antigen (PSA) Levels After Local Therapies (ARASTEP)
Biochemically Recurrent Prostate Cancer
About this trial
This is an interventional treatment trial for Biochemically Recurrent Prostate Cancer focused on measuring darolutamide, high risk BCR, PSMA PET imaging
Eligibility Criteria
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 (or refused) for 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 or central values accepted). 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.
Sites / Locations
- Mayo Clinic Hospital
- Arizona Institute of Urology
- City of Hope National Medical CenterRecruiting
- University of Southern California
- Tower Urology, IncRecruiting
- University of California, Los Angeles
- University of California Irvine Medical Center
- UCSF Med Center Helen Diller Family Comp Cancer Center
- Colorado Urology (Colorado Clinical Research)Recruiting
- Clermont Oncology Center
- University of Florida - Jacksonville
- Mid Florida Cancer Centers
- Northwestern University Feinberg School of Medicine
- Jesse Brown VA Medical Center
- Comprehensive Cancer Center
- Urology of Indiana, LLC
- First Urology PSC
- University of Kansas
- Chesapeake Urology Associates
- Johns Hopkins Univ School Med|Sidney Kimmel Comp Cancer Cntr
- Dana-Farber Cancer Institute
- UMass Memorial Medical Center - University Campus
- Barbara Ann Karmanos Cancer Institute - Detroit
- Michigan Institute of Urology, PC
- University of Minnesota Medical Center
- Washington University School of Medicine
- Urology Cancer Center, PC
- New Jersey Urology (NJU)
- New Jersey Urology, LLC
- NYU Langone Health
- Associated Medical Professionals of NY, PLLC
- White Plains Hospital
- Alliance UrologyRecruiting
- Wake Forest Baptist Health
- The Urology Group
- Ohio State University Wexner Medical Center
- MidLantic Urology
- Urological Associates of Lancaster
- Allegheny General Hospital
- University of Pittsburgh
- VA Pittsburgh Healthcare System
- Bon Secours St. Francis Hospital
- Carolina Urological Research Center
- Urology Austin, PLLC (an affiliate of Urology America)
- University of Texas MD Anderson Cancer Center
- Urology San Antonio Research, PA
- The Urology Place
- Spokane Urology PS
- Royal Prince Alfred Hospital
- South Western Sydney Local Health District | Liverpool Hospital - Stroke and Neurovascular Department
- Macquarie University Hospital
- GenesisCare Newcastle
- Port Macquarie Base Hospital
- St Vincents Hospital Sydney
- Sydney Adventist Hospital
- Westmead Hospital
- Bundaberg Hospital, Genesis Cancer Care - Bundaberg
- Wide Bay Hospital and Health Service - Hervey Bay Hospital
- Tasman Health Care
- Eastern Clinical Research Unit - Box Hill
- Epworth HealthCare
- Cabrini Medical Centre
- Royal Melbourne Hospital
- Austin Health
- Prince of Wales Hospital NSW
- Ordensklinikum Linz GmbH Elisabethinen
- Medizinische Universität Innsbruck
- Uniklinikum Salzburg - Landeskrankenhaus
- Krankenhaus der Barmherzigen Brüder
- Universitätsklinikum AKH Wien
- Assistência Multidisciplinar em Oncologia (AMO)
- Liga Paranaense de Combate ao Cancer-Hosp Erasto Gaertner
- Liga Norte Riograndense Contra o Cancer | Centro de Pesquisa Clínica
- Hospital Moinhos de Vento-Centro Clínico
- Faculdade de Medicina do ABC
- Instituto do Câncer do Estado de São Paulo
- Inst. de Assistência Médica ao Sérvidor Público Estadual
- Hospital Israelita Albert Einstein | Morumbi - Clinical Research Department
- Hospital Sirio Libanes
- Prostate Cancer Centre
- Vancouver General Hospital
- BCCA-Vancouver Island Centre
- Nova Scotia Health Authority
- Hamilton Health Sciences-Juravinski Cancer Centre
- London Regional Cancer Program
- Princess Margaret Cancer Centre - UHN
- Hopital Hotel-Dieu de Levis
- Sir Mortimer B. Davis Jewish General Hospital
- Centre Hospitalier Universitaire de Sherbrooke (CHUS) - Hopital Fleurimont
- Nanjing First Hospital
- Fudan University Shanghai Cancer Center
- The 1st Affiliated Hospital of Zhejiang University
- Peking Union Medical College Hospital (PUMCH) - East Location
- Aalborg University Hospital
- Aarhus Universitetshospital
- Rigshospitalet
- Docrates Klinikka
- HUS, Meilahden sairaala
- Oulun yliopistollinen sairaala
- Tampereen yliopistollinen sairaala, keskussairaala
- Turun yliopistollinen keskussairaala
- Hôpital Pellegrin - Bordeaux
- Centre Jean Perrin
- CHU GRENOBLE - Hopital Michallon
- Hôpital Claude Huriez - Lille
- Institut Curie - Ulm - Paris
- Hopital Bichat - Paris
- Centre Hospitalier Lyon Sud
- Institut de Cancérologie Jean Godinot
- Hôpital Pontchaillou
- Institue Curie - Saint-Cloud
- Institut de Cancérologie de l'Ouest - Saint Herblain
- ICANS - Institut de Cancérologie de Strasbourg Europe
- Hôpital Bretonneau
- Institut Gustave Roussy - Département de Médecine Oncologique
- Klinikum Mannheim GmbH
- Studienpraxis Urologie
- Klinikum rechts der Isar
- Klinikum der Universität Würzburg
- Universitätsklinikum der Johann Wolfgang Goethe Universität
- Städtisches Klinikum Braunschweig gGmbH
- Universitätsmedizin der Georg-August-Universität Göttingen
- Universitätsklinikum Köln
- Universitätsklinikum Münster (UKM)
- Medizinische Fakultät der Otto-von-Guericke Universität
- Universitätsklinikum Carl Gustav Carus Dresden
- Marien-Krankenhaus Bergisch Gladbach
- Vivantes Klinikum Am Urban
- Charité Campus Benjamin Franklin (CBF)
- Universitätsklinikum Jena - Institut für Diagnostische und Interventionelle Radiologie, Kinderradiologie
- Rambam Health Corporation
- Hadassah Hebrew University Hospital Ein Kerem
- Shaare Zedek Medical Center
- Clalit Health Services Rabin Medical Center-Beilinson Campus
- Sheba Medical Center
- Sourasky Medical Center
- Istituto Nazionale Tumori IRCCS Fondazione G.Pascale
- A.O.U. di Bologna Policlinico S.Orsola Malpighi
- AUSL di Bologna
- A.O.U. di Modena - Policlinico
- AUSL-IRCCS di Reggio Emilia
- IRCCS Centro di Riferimento Oncologico (CRO)
- Fondazione PTV Policlinico Tor Vergata
- IRCCS Istituti Fisioterapici Ospitalieri - IFO
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- ASST Papa Giovanni XXIII
- Istituto Clinico Humanitas - Humanitas Mirasole S.p.A.
- Ospedale San Raffaele s.r.l.
- Fondazione IRCCS Istituto Nazionale dei Tumori
- Molinette Hospital University of Torino
- A.O.U. Consorziale Policlinico
- A.O.U. Ospedali Riuniti Foggia
- Istituto Oncologico Veneto IRCCS (IOV)
- IRCCS Ospedale Sacro Cuore Don Calabria
- A.O.U.I. Verona
- IRCCS Ist Nazionale Tumori GE - Oncologia Medica
- A.O. di Perugia - Ospedale Santa Maria della Misericordia - DIAGNOSTICA PER IMMAGINI E RADIOTERAPIA
- Santa Chiara Hospital
- Hokkaido University Hospital
- Kanazawa University Hospital
- Yokohama City University Hospital
- Osaka University Hospital
- Tokyo Medical and Dental University Hospital
- Kagoshima University Hospital
- Kyoto University Hospital
- Auckland City Hosptial
- Canterbury Urology Research Trust
- Tauranga Urology Research Limited
- Centro Clinico Academico - Braga
- IPO Lisboa
- Hospital CUF Tejo
- Fundacao Champalimaud
- Hospital da Luz - Lisboa
- Centro Hospitalar Universitário de Lisboa Norte | Heart and Vessels Department
- Hospital Clínico Universitario de Santiago de Compostela
- Hospital del Mar
- Hospital Clínic i Provincial de Barcelona
- Hospital Fundació Puigvert
- Ciutat Sanitaria i Universitaria de la Vall d'Hebron
- Hospital Universitario Puerta del Mar
- MD Anderson International Espanya, S.A.
- Hospital Ramón y Cajal
- Hospital Madrid Norte Sanchinarro
- H. General Uiversitario Morales Meseguer - Department of Urology
- Hospital Universitario Virgen de la Victoria | Cardiology Department
- Virgen del Rocio University Hospital - Oncology Department
- Instituto Valenciano de Oncología
- Hospital Universitari i Politècnic La Fe
- Goteborgs Universitet
- Skane University Hospital - Department of Urology
- Uppsala Universitet - Akademiska Sjukhuset (Uppsala University Hospital)
- Bedford Hospital - Bedfordshire Hospitals NHS Foundation Tru
- Mount Vernon Cancer Centre
- Royal Surrey County Hospital NHS Foundation Trust
- University College London Hospitals NHS Foundation Trust
- Royal Marsden Hospital (London)
- Charing Cross Hospital
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Darolutamide+ADT
Placebo+ADT
Participants will receive darolutamide plus ADT twice daily with food for a pre-specified duration of 24 months.
Participants will receive Placebo plus ADT twice daily with food for a pre-specified duration of 24 months.