Prostatic NeoplasmsPhase 3ARANOTENCT04736199
Darolutamide in Addition to ADT Versus ADT in Metastatic Hormone-sensitive Prostate Cancer
A Phase 3 study testing Darolutamide (Nubeqa, BAY1841788) and Androgen deprivation therapy (ADT) in people with Prostatic Neoplasms, run by Bayer at 131 sites in 15 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostatic Neoplasms
- What is being tested?
- Darolutamide (Nubeqa, BAY1841788) and Androgen deprivation therapy (ADT)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 669 participants
- Where
- 131 sitesin 15 countries
- Study dates
- 23 Feb 2021to 23 Jan 2026
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
131 sites in 15 countries.
131 sites in 15 countries
China25 sites
Beijing Hospital
Beijing, Beijing Municipality, 100730
Cancer Hospital, Chinese Academy of Medical Sciences
Beijing, 100000
Peking University Third Hospital
Beijing, 100083
Beijing Cancer Hospital
Beijing, 100142
1st Hospital of Jilin University
Changchun, Jilin, 130021
Hunan Cancer Hospital - Oncology Department
Changsha, Hunan, 410013
SichuanAcademyofMedicalSciences&SichuanProvincialPeople'sHos
Chengdu, Sichuan, 610072
Sichuan University West China Hospital
Chengdu, Sichuan, MISSING
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, 510000
Guangzhou First People Hospital
Guangzhou, Guangdong, 510180
The 1st Affiliated Hospital of Zhejiang University
Hangzhou, Zhejiang, 310000
ZheJiang Provincial People's Hospital
Hangzhou, Zhejiang, 310014
Anhui Provincial Hospital
Hefei City, Anhui Province, Anhui, 230031
NJ Drum Tower Hospital, the Affil Hos of NJ Univ Med School
Nanjing, Jiangsu, 210008
Nantong tumor hospital
Nantong, Jiangsu, 226361
Ningbo First Hospital
Ningbo, Zhejiang, 315010
Liaoning Cancer Hospital and Institute
Shengyang, Liaoning, 110042
Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center
Shenzhen, Guangdong, 518172
The 2nd Affiliated Hospital of Soochow University
Suzhou, Jiangsu, 215004
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou, Zhejiang, 325000
Tongji Hosp. of Tongji Med Coll, Huazhong Uni of Sci & Tech.
Wuhan, Hubei, 430030
Zhongnan hospital ,Wuhan University
Wuhan, Hubei, 430071
Hubei Cancer Hospital
Wuhan, Hubei, 430079
The First Affiliated Hospital of Xi'an Jiaotong University
Xi’an, Shanxi, 710061
Yantai Yuhuangding Hospital
Yantai, Shandong, 264000
India23 sites
The Gujarat Cancer & Research Institute
Ahmedabad, Gujarat, 380016
HCG Cancer Centre - Ahmedabad
Ahmedabad, Gujarat, 380060
Marathwada Regional Cancer Centre and Research Institute
Aurangabad, Maharashtra, 431001
K.L.E.S. Dr. Prabhakar Kore Hospital & Medical Research Centre
Belagavi, Karnataka, 590010
Healthcare Global Enterprises Ltd
Bengaluru, Karnataka, 560027
Sparsh Hospital & Critical Care
Bhubaneswar, Odisha, 751007
All India Institute of Medical Sciences
Bhubaneswar, Odisha, 751019
Post Graduate Institute of Medical Education and Research
Chandigarh, 160012
Jawaharlal Institute Of Postgraduate Medical Education and R
Gorimedu, Puducherry, 605006
Sawami Man Singh (SMS) Medical College & Attached Hospitals
Jaipur, Rajasthan, 302017
Amrita Institute of Medical Sciences
Kochi, Kerala, 682 041
Tata Medical Center
Kolkata, 700156
Christian Medical Center & Hospital
Ludhiana, Punjab, 141008
Apollo Speciality Hospitals
Madurai, Tamil Nadu, 625020
Meenakshi Mission Hospital & Research Centre
Madurai, Tamil Nadu, 625107
Jaslok Hospital and Research Centre
Mumbai, Maharashtra, 400026
Curie Manavata Cancer Centre
Nashik, Maharashtra, 422004
Apex Wellness Hospital
Nashik, 422009
Rajiv Gandhi Cancer Institute & Research Centre
New Delhi, 110 085
Jehangir Hospital
Pune, Maharashtra, 411001
Regional Cancer Centre - Thiruvananthapuram
Thiruvananthapuram, Kerala, 695011
Cancer Care Clinic - Vadodara
Vadodara, Gujarat, 390007
Mahatma Gandhi Cancer Hospital & Research Institute
Visakhapatnam, Andhra Pradesh, 530017
Russia17 sites
Arkhangelsk Clinical Oncology Dispensary
Arkhangelsk, 163045
Ltd "EVIMED"
Chelyabinsk, 454048
Chelyabinsk Regional Oncology Dispensary
Chelyabinsk, 454087
Ivanovo Regional Oncology Dispensary
Ivanovo, 153040
Republican Clinical Oncology Dispensary Kazan
Kazan', 420029
Research Centre of X-ray and Radiology
Moscow, 117997
Volga District Med Center FMBA
Nizhny Novgorod, 603109
LLC Reafan
Novosibirsk, 630099
Medical Center "Avicenna"
Novosibirsk, 630099
Clinical Oncological Dispensary of Omsk Region
Omsk, 644013
AV Medical Group
Saint Petersburg, 196006
Russian Scientific Radiology and Surgery Technologies Center
Saint Petersburg, 197758
Scientific Research Instutute of Oncology n.a. N.N. Petrov
Saint Petersburg, 197758
Multi-Field Clinical Medical Center "Medical City"
Tyumen, 625041
Republican Clinical Oncology Dispensary
Ufa, 450054
Vologda Regional Hospital
Vologda, 160022
Sverdlovsk Regional Clinical Hospital #1
Yekaterinburg, 620102
Brazil16 sites
Fundacao Pio XII - Hospital de Cancer de Barretos
Barretos/SP, São Paulo, 14784-400
Hospital da Universidade Federal de Minas Gerais
Belo Horizonte, Minas Gerais, 30130-100
Cetus Oncologia Hospital Dia
Belo Horizonte, Minas Gerais, 30150-270
Liga Paranaense de Combate ao Cancer-Hosp Erasto Gaertner
Curitiba, Paraná, 81520-060
Hosp. Araujo Jorge da Associação de Combate ao Câncer
Goiânia, Goiás, 74605-070
Liga Norte Riograndense Contra o Cancer | Centro de Pesquisa Clínica
Natal, Rio Grande do Norte, 59040-000
Unidade de Pesquisas Clinicas em Oncologia
Pelotas, Rio Grande do Sul, 96020-080
Santa Casa de Porto Alegre | Hospital Sao Francisco - Centro Medico Pesquisa Clinica Cardiologia
Porto Alegre, Rio Grande do Sul, 90020-090
Hospital Mae de Deus
Porto Alegre, Rio Grande do Sul, 90850-170
FZ Pesquisa e Servicos em Cardiologia | Porto Alegre, Brazil
Porto Alegre, Rio Grande do Sul, 91350-280
Instituto COI de Educação e Pesquisa
Rio de Janeiro, 22793-080
Assistência Multidisciplinar em Oncologia (AMO)
Salvador, Estado de Bahia, 41950-640
Hospital de Base | Funfarme - Centro Integrado de Pesquisa - Cardiologia
São José do Rio Preto, São Paulo, 15090-000
Urobrasil
São Paulo, São Paulo, 01243-020
IBCC - Instituto Brasileiro de Controle do Cancer
São Paulo, São Paulo, 03102-002
Inst. de Assistência Médica ao Sérvidor Público Estadual
São Paulo, São Paulo, 04039-004
Chile7 sites
Centro de Estudios Clínicos SAGA SpA
Providencia, Santiago Metropolitan, 7500653
Fundación Arturo López Perez
Santiago, 7500921
Oncovida
Santiago, 7510032
Hospital Clínico de la Pontificia Univ. Católica de Chile
Santiago, TBC
UROMED
Santiago
Centro de Investigación Clínica del Sur
Temuco, Araucania, 4781156
OncoCentro
Viña del Mar, Valparaiso, 2520598
Australia6 sites
Cancer Research South Australia
Adelaide, South Australia, 5000
Peninsula Oncology Centre
Frankston, Victoria, 3199
Austin Health
Heidelberg, Victoria, 3084
Nepean Hospital
Kingswood, New South Wales, 2747
Northern Cancer Institute
St Leonards, New South Wales, 2065
Macquarie University Hospital - Oncology Department
Sydney, New South Wales, 2109
Spain6 sites
Hospital Universitario Fundacion Alcorcon | Urologia
Alcorcón, Madrid, 28922
Fundacio Puigvert | Urologia
Barcelona, 08025
Parc Tauli Hospital Universitari | Oncologia
Barcelona, 08208
Hospital San Pedro De Alcantara | Oncologia
Cáceres, 10003
Hospital Universitario Virgen De La Victoria | Urologia
Málaga, 20910
Hospital Universitario Virgen Del Rocio S.L. | Urologia
Seville, 41013
Latvia5 sites
Daugavpils Regional Hospital
Daugavpils, LV-5417
RAKUS Hospital Gailezers
Riga, 1038
URO Ltd.
Riga, LV-1001
P. Stradins Clinical University Hospital
Riga, LV-1002
Vidzemes Hospital
Valmiera, LV-4201
Taiwan5 sites
Changhua Christian Hospital
Changhua, 50006
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, Kaohsiung, 807377
Taichung Veterans General Hospital
Taichung, 40705
National Cheng Kung University Hospital
Tainan, 704
Taipei Veterans General Hospital
Taipei, 11217
Lithuania4 sites
The Hospital of Lithuanian University of Health SciencesLUHS
Kaunas, LT-50009
PI Klaipedos University Hospital
Klaipėda, LT-92288
National Cancer Institute
Vilnius, LT-08660
Vilnius University Hospital Santaros Klinikos
Vilnius, LT-08661
Peru4 sites
Hospital Militar Luis Arias Schreiber
Lima, LIMA 11
Clínica El Golf
Lima, LIMA 27
Aliada
San Isidro, Lima region, 15036
Hospital Guillermo Almenara Irigoyen
Santiago de Surco, Lima region, 15033
South Africa4 sites
Cape Town Oncology Trials
Cape Town, 7570
East Rand Medical Research Unit
Johannesburg, Gauteng, 1475
Cancercare Langenhoven
Port Elizabeth, Eastern Cape, 6045
University of Pretoria, Clinical Research Unit
Pretoria, Gauteng, 2
Ukraine4 sites
CNE "Clinical Center of Oncology, Hematology, Transplantology and Palliative Care of the Cherkasy Regional Council"
Cherkasy, 18009
City Dnipropetrovsk Multi- field Clinical Hosp. 4 DSMA
Dnipro, 49102
Kyiv City Hospital #3 - Department of Urology
Kyiv, 02660
Kyiv Regional Oncological Dispensary
Kyiv, 4107
New Zealand3 sites
Canterbury Urology Research Trust
Christchurch, Canterbury, 8013
Waikato Hospital
Hamilton, Waikato Region, 3240
Tauranga Urology Research Limited
Tauranga, Bay of Plenty, 3112
Canada2 sites
G. Kenneth Jansz Medicine Professional Corporation
Burlington, Ontario, L7N 3V2
Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM)
Montreal, Quebec, H2X 0A9
About this study
Official title: 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)
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.
- Conditions
- Prostatic Neoplasms
- Being tested
- Darolutamide (Nubeqa, BAY1841788), Placebo, Androgen deprivation therapy (ADT)
- Keywords
- Metastatic hormone-sensitive prostate cancer
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Darolutamide (Nubeqa, BAY1841788)Drug
Coated tablet, oral administration
PlaceboDrug
Coated tablet matching Darolutamide in appearance, oral administration
Androgen deprivation therapy (ADT)Other
Luteinizing hormone-releasing hormone (LHRH) agonist/antagonists or orchiectomy
| Study group | Role | What they receive |
|---|---|---|
| Darolutamide+ADT | Experimental | Participants will receive darolutamide 600 mg (2 tablets of 300 mg) twice daily with food and ADT of investigator's choice as standard therapy Receives: Drug: Darolutamide (Nubeqa, BAY1841788); Other: Androgen deprivation therapy (ADT) |
| Placebo+ADT | Placebo comparator | Participants will receive placebo twice daily with food and ADT of investigator's choice as standard therapy Receives: Drug: Placebo; Other: Androgen deprivation therapy (ADT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From randomization to the date when 222 rPFS events were observed, approximately 36 months
Secondary outcomes (7)
Overall Survival (OS)
Time from the date of randomization to the date of death from any cause.
Measured: From randomization to the final analysis date, approximately 47 months
Time to Castration-Resistant Prostate Cancer (CRPC)
Time from the date of randomization to the date of first castration resistant event (radiological progression, Prostate-specific antigen (PSA) progression or symptomatic skeletal events, whichever occurs first).
Measured: From randomization to the date when 222 rPFS events were observed, approximately 36 months
Time to Initiation of Subsequent Anti-cancer Therapy
Time from the date of randomization to initiation of first subsequent anti-cancer therapy for prostate cancer.
Measured: From randomization to the date when 222 rPFS events were observed, approximately 36 months
Time to PSA Progression
Time from the date of randomization to the date of first prostate-specific antigen (PSA) progression. PSA progression with serum testosterone being at castrate level <0.50 ng/mL, is defined as a ≥25% increase above the nadir (lowest at or after baseline) value and an increase in absolute value of ≥2 ng/mL above nadir, and is at least 12 weeks from randomization date, which is confirmed by a second value 3 or more weeks later. All PSA values between the initial assessment meeting the PSA progression criteria and confirmation assessment must be ≥2 ng/mL and ≥25% increase above nadir, serum testosterone at castrate levels <0.50 ng/mL is requested at initial assessment.
Measured: From randomization to the date when 222 rPFS events were observed, approximately 36 months
PSA Undetectable Rates (<0.2 ng/mL)
Percentage of subjects with detectable PSA values of ≥0.2 ng/mL at baseline which became undetectable with any PSA values <0.2 ng/mL during the period between randomization and 30 days after last dose of study drug or start of new anti-cancer therapy whichever occurred earliest, based on the subjects had detectable PSA value at baseline.
Measured: From randomization to the date when 222 rPFS events were observed, approximately 36 months
Time to Pain Progression
Pain progression was assessed by Question 3 (Q3) of the BPI-SF questionnaire related to the worst pain in the last 24 hours (worst pain subscale [WPS]) taken as an average for post baseline score, or initiation of short or long-acting opioids for malignant disease for ≥7 consecutive days after randomization. Pain progression was defined as: (1) for asymptomatic subjects with WPS=0 at baseline, an increase of 2 or more points in the WPS score from nadir observed at 2 consecutive evaluations ≥4 weeks apart, or initiation of short- or long-acting opioid use for malignant disease for ≥7 consecutive days after randomization; (2) for symptomatic subjects with WPS >0 at baseline, an increase of 2 or more points in the WPS score from nadir observed at 2 consecutive evaluations ≥4 weeks apart and a WPS ≥5, or initiation of short- or long-acting opioid use for malignant disease for ≥7 consecutive days after randomization.
Measured: From randomization to the date when 222 rPFS events were observed, approximately 36 months
Number of Participants With Adverse Events as a Measure of Safety
An AE is any untoward medical occurrence in a patient or clinical study participant, after providing written IC for participation in the study, may or may not be temporally associated with the use of study drug, whether or not considered related to the study drug. Treatment-emergent AE (TEAE) is defined as any event arising or worsening after the first dose of study drug until 30 days after the last dose of study drug.
Measured: From start of study drug administration until 30 days after the last administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2021
- Study start23 Feb 2021
- Primary completion7 Jun 2024
- Study completion23 Jan 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Prostatic NeoplasmsStudies of the same condition, open and under way.
- More trials run by BayerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 669 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Orion Corporation, Orion Pharma
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04736199
- Sponsor's protocol ID
- 21140
- Other IDs
- 2022-502244-12-00, 2020-003093-48
- Acronym
- ARANOTE
- Status last verified
- Sep 2026
- First submitted
- 29 Jan 2021
- Last updated
- 29 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: 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.
Publications
Saad F, Shore N, Vjaters E, Olmos D, Littleton N, Testa I, Mo M, Verholen F, Srinivasan S, Haresh KP. Darolutamide Plus Androgen-deprivation Therapy in Metastatic Hormone-sensitive Prostate Cancer by Disease Volume and Risk Subgroups in the Phase 3 ARANOTE Trial. Eur Urol. 2026 Aug 12:S0302-2838(26)02313-4. doi: 10.1016/j.eururo.2026.07.026. Online ahead of print.
PubMed 42586872Morgans AK, Haresh KP, Jievaltas M, Olmos D, Shore ND, Vjaters E, Xing N, Mohamed AF, Littleton N, Srinivasan S, Verholen F, Saad F. Pain and health-related quality-of-life outcomes with darolutamide in metastatic hormone-sensitive prostate cancer (ARANOTE): secondary and exploratory analyses of a multicentre, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2026 May;27(5):614-624. doi: 10.1016/S1470-2045(26)00014-8. Epub 2026 Apr 9.
PubMed 41969015Saad 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.
PubMed 39279580