Darolutamide in Addition to ADT Versus ADT in Metastatic Hormone-sensitive Prostate Cancer
ARANOTE
A Randomized, Double-blind, Placebo-controlled Phase 3 Study of Darolutamide in Addition to Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Men With Metastatic Hormone-sensitive Prostate Cancer (mHSPC)
3 other identifiers
interventional
669
15 countries
131
Brief Summary
The purpose of the study is to assess the efficacy and safety of darolutamide in combination with standard androgen deprivation therapy (ADT) in patients with metastatic hormone sensitive prostate cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Feb 2021
Longer than P75 for phase_3
131 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 29, 2021
CompletedFirst Posted
Study publicly available on registry
February 3, 2021
CompletedStudy Start
First participant enrolled
February 23, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 7, 2024
CompletedResults Posted
Study results publicly available
August 8, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
January 23, 2026
CompletedFebruary 27, 2026
January 1, 2026
3.3 years
January 29, 2021
May 22, 2025
February 9, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Radiological Progression-free Survival (rPFS) Assessed by Central Review
rPFS used conventional imaging method (99mTc-phosphonate bone scan, CT/MRI scan). rPFS was defined as the time from the date of randomization to the date of progressive disease in malignant soft tissue lesions, progressive disease in malignant bone lesions, or death due to any cause, whichever occurs first. Malignant soft tissue lesions were assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and malignant bone lesions were assessed by Prostate Cancer Clinical Trials Working Group (PCWG3) criteria.
From randomization to the date when 222 rPFS events were observed, approximately 36 months
Secondary Outcomes (7)
Overall Survival (OS)
From randomization to the date when 222 rPFS events were observed, approximately 36 months
Time to Castration-Resistant Prostate Cancer (CRPC)
From randomization to the date when 222 rPFS events were observed, approximately 36 months
Time to Initiation of Subsequent Anti-cancer Therapy
From randomization to the date when 222 rPFS events were observed, approximately 36 months
Time to PSA Progression
From randomization to the date when 222 rPFS events were observed, approximately 36 months
PSA Undetectable Rates (<0.2 ng/mL)
From randomization to the date when 222 rPFS events were observed, approximately 36 months
- +2 more secondary outcomes
Study Arms (2)
Darolutamide+ADT
EXPERIMENTALParticipants will receive darolutamide 600 mg (2 tablets of 300 mg) twice daily with food and ADT of investigator's choice as standard therapy
Placebo+ADT
PLACEBO COMPARATORParticipants will receive placebo twice daily with food and ADT of investigator's choice as standard therapy
Interventions
Luteinizing hormone-releasing hormone (LHRH) agonist/antagonists or orchiectomy
Eligibility Criteria
You may qualify if:
- Histologically or cytologically confirmed adenocarcinoma of prostate
- Metastatic disease
- Started ADT (LHRH agonist/antagonist or orchiectomy) with or without first generation anti-androgen, but not earlier than 12 weeks before randomization
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1 or 2
- Adequate bone marrow, liver and renal function
You may not qualify if:
- Prior treatment with: LHRH agonist/antagonists except neoadjuvant and /or adjuvant therapy; Second-generation androgen receptor (AR) inhibitors such as enzalutamide, darolutamide, apalutamide or other investigational AR inhibitors; Cytochrome P17 enzyme inhibitor such as abiraterone acetate or oral ketoconazole as anti-cancer treatment for prostate cancer; Chemotherapy including docetaxel or immunotherapy for prostate cancer; Use of systemic corticosteroid with dose greater than the equivalent 10 mg of prednisone/day within 28 days prior to randomization; Radiopharmaceuticals; Any other anti-cancer treatment for prostate cancer, excluding local therapies and ADT.
- Treatment with radiotherapy within 2 weeks before randomization
- Contraindication to iodinated CT and gadolinium chelate MRI intravenous contrast agent(s)
- Had any of the following within 6 months before randomization: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, congestive heart failure (New York Heart Association Class III or IV)
- Uncontrolled hypertension as indicated by a resting systolic BP ≥ 160 mmHg or diastolic BP ≥ 100 mmHg despite medical management
- A gastrointestinal (GI) disorder or procedure which is expected to interfere significantly with absorption of study drug
- 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 prior to randomization
- Inability to swallow oral medications
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Bayerlead
- Orion Corporation, Orion Pharmacollaborator
Study Sites (131)
Nepean Hospital
Kingswood, New South Wales, 2747, Australia
Northern Cancer Institute
St Leonards, New South Wales, 2065, Australia
Macquarie University Hospital - Oncology Department
Sydney, New South Wales, 2109, Australia
Cancer Research South Australia
Adelaide, South Australia, 5000, Australia
Peninsula Oncology Centre
Frankston, Victoria, 3199, Australia
Austin Health
Heidelberg, Victoria, 3084, Australia
Assistência Multidisciplinar em Oncologia (AMO)
Salvador, Estado de Bahia, 41950-640, Brazil
Hosp. Araujo Jorge da Associação de Combate ao Câncer
Goiânia, Goiás, 74605-070, Brazil
Hospital da Universidade Federal de Minas Gerais
Belo Horizonte, Minas Gerais, 30130-100, Brazil
Cetus Oncologia Hospital Dia
Belo Horizonte, Minas Gerais, 30150-270, Brazil
Liga Paranaense de Combate ao Cancer-Hosp Erasto Gaertner
Curitiba, Paraná, 81520-060, Brazil
Liga Norte Riograndense Contra o Cancer | Centro de Pesquisa Clínica
Natal, Rio Grande do Norte, 59040-000, Brazil
Unidade de Pesquisas Clinicas em Oncologia
Pelotas, Rio Grande do Sul, 96020-080, Brazil
Santa Casa de Porto Alegre | Hospital Sao Francisco - Centro Medico Pesquisa Clinica Cardiologia
Porto Alegre, Rio Grande do Sul, 90020-090, Brazil
Hospital Mae de Deus
Porto Alegre, Rio Grande do Sul, 90850-170, Brazil
FZ Pesquisa e Servicos em Cardiologia | Porto Alegre, Brazil
Porto Alegre, Rio Grande do Sul, 91350-280, Brazil
Fundacao Pio XII - Hospital de Cancer de Barretos
Barretos/SP, São Paulo, 14784-400, Brazil
Hospital de Base | Funfarme - Centro Integrado de Pesquisa - Cardiologia
São José do Rio Preto, São Paulo, 15090-000, Brazil
Urobrasil
São Paulo, São Paulo, 01243-020, Brazil
IBCC - Instituto Brasileiro de Controle do Cancer
São Paulo, São Paulo, 03102-002, Brazil
Inst. de Assistência Médica ao Sérvidor Público Estadual
São Paulo, São Paulo, 04039-004, Brazil
Instituto COI de Educação e Pesquisa
Rio de Janeiro, 22793-080, Brazil
G. Kenneth Jansz Medicine Professional Corporation
Burlington, Ontario, L7N 3V2, Canada
Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM)
Montreal, Quebec, H2X 0A9, Canada
Centro de Investigación Clínica del Sur
Temuco, Región de la Araucanía, 4781156, Chile
OncoCentro
Viña del Mar, Región de Valparaíso, 2520598, Chile
Centro de Estudios Clínicos SAGA SpA
Providencia, Santiago Metropolitan, 7500653, Chile
Fundación Arturo López Perez
Santiago, 7500921, Chile
Oncovida
Santiago, 7510032, Chile
Hospital Clínico de la Pontificia Univ. Católica de Chile
Santiago, TBC, Chile
UROMED
Santiago, Chile
Anhui Provincial Hospital
Hefei City, Anhui Province, Anhui, 230031, China
Beijing Hospital
Beijing, Beijing Municipality, 100730, China
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, 510000, China
Guangzhou First People Hospital
Guangzhou, Guangdong, 510180, China
Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center
Shenzhen, Guangdong, 518172, China
Tongji Hosp. of Tongji Med Coll, Huazhong Uni of Sci & Tech.
Wuhan, Hubei, 430030, China
Zhongnan hospital ,Wuhan University
Wuhan, Hubei, 430071, China
Hubei Cancer Hospital
Wuhan, Hubei, 430079, China
Hunan Cancer Hospital - Oncology Department
Changsha, Hunan, 410013, China
NJ Drum Tower Hospital, the Affil Hos of NJ Univ Med School
Nanjing, Jiangsu, 210008, China
Nantong tumor hospital
Nantong, Jiangsu, 226361, China
The 2nd Affiliated Hospital of Soochow University
Suzhou, Jiangsu, 215004, China
1st Hospital of Jilin University
Changchun, Jilin, 130021, China
Liaoning Cancer Hospital and Institute
Shengyang, Liaoning, 110042, China
Yantai Yuhuangding Hospital
Yantai, Shandong, 264000, China
The First Affiliated Hospital of Xi'an Jiaotong University
Xi’an, Shanxi, 710061, China
SichuanAcademyofMedicalSciences&SichuanProvincialPeople'sHos
Chengdu, Sichuan, 610072, China
Sichuan University West China Hospital
Chengdu, Sichuan, MISSING, China
The 1st Affiliated Hospital of Zhejiang University
Hangzhou, Zhejiang, 310000, China
ZheJiang Provincial People's Hospital
Hangzhou, Zhejiang, 310014, China
Ningbo First Hospital
Ningbo, Zhejiang, 315010, China
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou, Zhejiang, 325000, China
Cancer Hospital, Chinese Academy of Medical Sciences
Beijing, 100000, China
Peking University Third Hospital
Beijing, 100083, China
Beijing Cancer Hospital
Beijing, 100142, China
Mahatma Gandhi Cancer Hospital & Research Institute
Visakhapatnam, Andhra Pradesh, 530017, India
The Gujarat Cancer & Research Institute
Ahmedabad, Gujarat, 380016, India
HCG Cancer Centre - Ahmedabad
Ahmedabad, Gujarat, 380060, India
Cancer Care Clinic - Vadodara
Vadodara, Gujarat, 390007, India
K.L.E.S. Dr. Prabhakar Kore Hospital & Medical Research Centre
Belagavi, Karnataka, 590010, India
Healthcare Global Enterprises Ltd
Bengaluru, Karnataka, 560027, India
Amrita Institute of Medical Sciences
Kochi, Kerala, 682 041, India
Regional Cancer Centre - Thiruvananthapuram
Thiruvananthapuram, Kerala, 695011, India
Marathwada Regional Cancer Centre and Research Institute
Aurangabad, Maharashtra, 431001, India
Jaslok Hospital and Research Centre
Mumbai, Maharashtra, 400026, India
Curie Manavata Cancer Centre
Nashik, Maharashtra, 422004, India
Jehangir Hospital
Pune, Maharashtra, 411001, India
Sparsh Hospital & Critical Care
Bhubaneswar, Odisha, 751007, India
All India Institute of Medical Sciences
Bhubaneswar, Odisha, 751019, India
Jawaharlal Institute Of Postgraduate Medical Education and R
Gorimedu, Puducherry, 605006, India
Christian Medical Center & Hospital
Ludhiana, Punjab, 141008, India
Sawami Man Singh (SMS) Medical College & Attached Hospitals
Jaipur, Rajasthan, 302017, India
Apollo Speciality Hospitals
Madurai, Tamil Nadu, 625020, India
Meenakshi Mission Hospital & Research Centre
Madurai, Tamil Nadu, 625107, India
Post Graduate Institute of Medical Education and Research
Chandigarh, 160012, India
Tata Medical Center
Kolkata, 700156, India
Apex Wellness Hospital
Nashik, 422009, India
Rajiv Gandhi Cancer Institute & Research Centre
New Delhi, 110 085, India
Daugavpils Regional Hospital
Daugavpils, LV-5417, Latvia
RAKUS Hospital Gailezers
Riga, 1038, Latvia
URO Ltd.
Riga, LV-1001, Latvia
P. Stradins Clinical University Hospital
Riga, LV-1002, Latvia
Vidzemes Hospital
Valmiera, LV-4201, Latvia
The Hospital of Lithuanian University of Health SciencesLUHS
Kaunas, LT-50009, Lithuania
PI Klaipedos University Hospital
Klaipėda, LT-92288, Lithuania
National Cancer Institute
Vilnius, LT-08660, Lithuania
Vilnius University Hospital Santaros Klinikos
Vilnius, LT-08661, Lithuania
Tauranga Urology Research Limited
Tauranga, Bay of Plenty, 3112, New Zealand
Canterbury Urology Research Trust
Christchurch, Canterbury, 8013, New Zealand
Waikato Hospital
Hamilton, Waikato Region, 3240, New Zealand
Aliada
San Isidro, Lima region, 15036, Peru
Hospital Guillermo Almenara Irigoyen
Santiago de Surco, Lima region, 15033, Peru
Hospital Militar Luis Arias Schreiber
Lima, LIMA 11, Peru
Clínica El Golf
Lima, LIMA 27, Peru
Arkhangelsk Clinical Oncology Dispensary
Arkhangelsk, 163045, Russia
Ltd "EVIMED"
Chelyabinsk, 454048, Russia
Chelyabinsk Regional Oncology Dispensary
Chelyabinsk, 454087, Russia
Ivanovo Regional Oncology Dispensary
Ivanovo, 153040, Russia
Republican Clinical Oncology Dispensary Kazan
Kazan', 420029, Russia
Research Centre of X-ray and Radiology
Moscow, 117997, Russia
Volga District Med Center FMBA
Nizhny Novgorod, 603109, Russia
LLC Reafan
Novosibirsk, 630099, Russia
Medical Center "Avicenna"
Novosibirsk, 630099, Russia
Clinical Oncological Dispensary of Omsk Region
Omsk, 644013, Russia
AV Medical Group
Saint Petersburg, 196006, Russia
Russian Scientific Radiology and Surgery Technologies Center
Saint Petersburg, 197758, Russia
Scientific Research Instutute of Oncology n.a. N.N. Petrov
Saint Petersburg, 197758, Russia
Multi-Field Clinical Medical Center "Medical City"
Tyumen, 625041, Russia
Republican Clinical Oncology Dispensary
Ufa, 450054, Russia
Vologda Regional Hospital
Vologda, 160022, Russia
Sverdlovsk Regional Clinical Hospital #1
Yekaterinburg, 620102, Russia
Cancercare Langenhoven
Port Elizabeth, Eastern Cape, 6045, South Africa
East Rand Medical Research Unit
Johannesburg, Gauteng, 1475, South Africa
University of Pretoria, Clinical Research Unit
Pretoria, Gauteng, 2, South Africa
Cape Town Oncology Trials
Cape Town, 7570, South Africa
Hospital Universitario Fundacion Alcorcon | Urologia
Alcorcón, Madrid, 28922, Spain
Fundacio Puigvert | Urologia
Barcelona, 08025, Spain
Parc Tauli Hospital Universitari | Oncologia
Barcelona, 08208, Spain
Hospital San Pedro De Alcantara | Oncologia
Cáceres, 10003, Spain
Hospital Universitario Virgen De La Victoria | Urologia
Málaga, 20910, Spain
Hospital Universitario Virgen Del Rocio S.L. | Urologia
Seville, 41013, Spain
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, Kaohsiung, 807377, Taiwan
Changhua Christian Hospital
Changhua, 50006, Taiwan
Taichung Veterans General Hospital
Taichung, 40705, Taiwan
National Cheng Kung University Hospital
Tainan, 704, Taiwan
Taipei Veterans General Hospital
Taipei, 11217, Taiwan
CNE "Clinical Center of Oncology, Hematology, Transplantology and Palliative Care of the Cherkasy Regional Council"
Cherkasy, 18009, Ukraine
City Dnipropetrovsk Multi- field Clinical Hosp. 4 DSMA
Dnipro, 49102, Ukraine
Kyiv City Hospital #3 - Department of Urology
Kyiv, 02660, Ukraine
Kyiv Regional Oncological Dispensary
Kyiv, 4107, Ukraine
Related Publications (1)
Saad F, Vjaters E, Shore N, Olmos D, Xing N, Pereira de Santana Gomes AJ, Cesar de Andrade Mota A, Salman P, Jievaltas M, Ulys A, Jakubovskis M, Kopyltsov E, Han W, Nevalaita L, Testa I, Le Berre MA, Kuss I, Haresh KP; ARANOTE Study Investigators. Darolutamide in Combination With Androgen-Deprivation Therapy in Patients With Metastatic Hormone-Sensitive Prostate Cancer From the Phase III ARANOTE Trial. J Clin Oncol. 2024 Dec 20;42(36):4271-4281. doi: 10.1200/JCO-24-01798. Epub 2024 Sep 16.
PMID: 39279580DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Therapeutic Area Head
- Organization
- Bayer AG
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 29, 2021
First Posted
February 3, 2021
Study Start
February 23, 2021
Primary Completion
June 7, 2024
Study Completion
January 23, 2026
Last Updated
February 27, 2026
Results First Posted
August 8, 2025
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will not share
Availability of this study's data will 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.clinicalstudydatarequest.com 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 Study sponsors section of the portal.