Darolutamide in Addition to ADT Versus ADT in Metastatic Hormone-sensitive Prostate Cancer

NCT ID: NCT04736199

Last Updated: 2026-01-14

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 669 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-23
• Study Completion Date: 2026-01-30

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.

Conditions

Prostatic Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Darolutamide+ADT

Participants will receive darolutamide 600 mg (2 tablets of 300 mg) twice daily with food and ADT of investigator's choice as standard therapy

Group Type: EXPERIMENTAL

Darolutamide (Nubeqa, BAY1841788)

Intervention Type: DRUG

Coated tablet, oral administration

Androgen deprivation therapy (ADT)

Intervention Type: OTHER

Luteinizing hormone-releasing hormone (LHRH) agonist/antagonists or orchiectomy

Placebo+ADT

Participants will receive placebo twice daily with food and ADT of investigator's choice as standard therapy

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Coated tablet matching Darolutamide in appearance, oral administration

Androgen deprivation therapy (ADT)

Intervention Type: OTHER

Luteinizing hormone-releasing hormone (LHRH) agonist/antagonists or orchiectomy

Interventions

Darolutamide (Nubeqa, BAY1841788)

Coated tablet, oral administration

Intervention Type: DRUG

Placebo

Coated tablet matching Darolutamide in appearance, oral administration

Intervention Type: DRUG

Androgen deprivation therapy (ADT)

Luteinizing hormone-releasing hormone (LHRH) agonist/antagonists or orchiectomy

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Orion Corporation, Orion Pharma

INDUSTRY

Sponsor Role: collaborator

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Nepean Hospital

Kingswood, New South Wales, Australia

Northern Cancer Institute

St Leonards, New South Wales, Australia

Macquarie University Hospital - Oncology Department

Sydney, New South Wales, Australia

Cancer Research South Australia

Adelaide, South Australia, Australia

Peninsula Oncology Centre

Frankston, Victoria, Australia

Austin Health

Heidelberg, Victoria, Australia

Assistência Multidisciplinar em Oncologia (AMO)

Salvador, Estado de Bahia, Brazil

Hosp. Araujo Jorge da Associação de Combate ao Câncer

Goiânia, Goiás, Brazil

Hospital da Universidade Federal de Minas Gerais

Belo Horizonte, Minas Gerais, Brazil

Cetus Oncologia Hospital Dia

Belo Horizonte, Minas Gerais, Brazil

Liga Paranaense de Combate ao Cancer-Hosp Erasto Gaertner

Curitiba, Paraná, Brazil

Liga Norte Riograndense Contra o Cancer | Centro de Pesquisa Clínica

Natal, Rio Grande do Norte, Brazil

Unidade de Pesquisas Clinicas em Oncologia

Pelotas, Rio Grande do Sul, Brazil

Santa Casa de Porto Alegre | Hospital Sao Francisco - Centro Medico Pesquisa Clinica Cardiologia

Porto Alegre, Rio Grande do Sul, Brazil

Hospital Mae de Deus

Porto Alegre, Rio Grande do Sul, Brazil

FZ Pesquisa e Servicos em Cardiologia | Porto Alegre, Brazil

Porto Alegre, Rio Grande do Sul, Brazil

Fundacao Pio XII - Hospital de Cancer de Barretos

Barretos/SP, São Paulo, Brazil

Hospital de Base | Funfarme - Centro Integrado de Pesquisa - Cardiologia

São José do Rio Preto, São Paulo, Brazil

Urobrasil

São Paulo, São Paulo, Brazil

IBCC - Instituto Brasileiro de Controle do Cancer

São Paulo, São Paulo, Brazil

Inst. de Assistência Médica ao Sérvidor Público Estadual

São Paulo, São Paulo, Brazil

Instituto COI de Educação e Pesquisa

Rio de Janeiro, , Brazil

G. Kenneth Jansz Medicine Professional Corporation

Burlington, Ontario, Canada

Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM)

Montreal, Quebec, Canada

Centro de Investigación Clínica del Sur

Temuco, Región de la Araucanía, Chile

OncoCentro

Viña del Mar, Región de Valparaíso, Chile

Centro de Estudios Clínicos SAGA SpA

Providencia, Santiago Metropolitan, Chile

Fundación Arturo López Perez

Santiago, , Chile

Oncovida

Santiago, , Chile

Hospital Clínico de la Pontificia Univ. Católica de Chile

Santiago, , Chile

UROMED

Santiago, , Chile

Anhui Provincial Hospital

Hefei City, Anhui Province, Anhui, China

Beijing Hospital

Beijing, Beijing Municipality, China

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Guangzhou First People Hospital

Guangzhou, Guangdong, China

Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center

Shenzhen, Guangdong, China

Tongji Hosp. of Tongji Med Coll, Huazhong Uni of Sci & Tech.

Wuhan, Hubei, China

Zhongnan hospital ,Wuhan University

Wuhan, Hubei, China

Hubei Cancer Hospital

Wuhan, Hubei, China

Hunan Cancer Hospital - Oncology Department

Changsha, Hunan, China

NJ Drum Tower Hospital, the Affil Hos of NJ Univ Med School

Nanjing, Jiangsu, China

Nantong tumor hospital

Nantong, Jiangsu, China

The 2nd Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

1st Hospital of Jilin University

Changchun, Jilin, China

Liaoning Cancer Hospital and Institute

Shengyang, Liaoning, China

Yantai Yuhuangding Hospital

Yantai, Shandong, China

The First Affiliated Hospital of Xi'an Jiaotong University

Xi’an, Shanxi, China

SichuanAcademyofMedicalSciences&SichuanProvincialPeople'sHos

Chengdu, Sichuan, China

Sichuan University West China Hospital

Chengdu, Sichuan, China

The 1st Affiliated Hospital of Zhejiang University

Hangzhou, Zhejiang, China

ZheJiang Provincial People's Hospital

Hangzhou, Zhejiang, China

Ningbo First Hospital

Ningbo, Zhejiang, China

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China

Cancer Hospital, Chinese Academy of Medical Sciences

Beijing, , China

Peking University Third Hospital

Beijing, , China

Beijing Cancer Hospital

Beijing, , China

Mahatma Gandhi Cancer Hospital & Research Institute

Visakhapatnam, Andhra Pradesh, India

The Gujarat Cancer & Research Institute

Ahmedabad, Gujarat, India

HCG Cancer Centre - Ahmedabad

Ahmedabad, Gujarat, India

Cancer Care Clinic - Vadodara

Vadodara, Gujarat, India

K.L.E.S. Dr. Prabhakar Kore Hospital & Medical Research Centre

Belagavi, Karnataka, India

Healthcare Global Enterprises Ltd

Bengaluru, Karnataka, India

Amrita Institute of Medical Sciences

Kochi, Kerala, India

Regional Cancer Centre - Thiruvananthapuram

Thiruvananthapuram, Kerala, India

Marathwada Regional Cancer Centre and Research Institute

Aurangabad, Maharashtra, India

Jaslok Hospital and Research Centre

Mumbai, Maharashtra, India

Curie Manavata Cancer Centre

Nashik, Maharashtra, India

Jehangir Hospital

Pune, Maharashtra, India

Sparsh Hospital & Critical Care

Bhubaneswar, Odisha, India

All India Institute of Medical Sciences

Bhubaneswar, Odisha, India

Jawaharlal Institute Of Postgraduate Medical Education and R

Gorimedu, Puducherry, India

Christian Medical Center & Hospital

Ludhiana, Punjab, India

Sawami Man Singh (SMS) Medical College & Attached Hospitals

Jaipur, Rajasthan, India

Apollo Speciality Hospitals

Madurai, Tamil Nadu, India

Meenakshi Mission Hospital & Research Centre

Madurai, Tamil Nadu, India

Post Graduate Institute of Medical Education and Research

Chandigarh, , India

Tata Medical Center

Kolkata, , India

Apex Wellness Hospital

Nashik, , India

Rajiv Gandhi Cancer Institute & Research Centre

New Delhi, , India

Daugavpils Regional Hospital

Daugavpils, , Latvia

RAKUS Hospital Gailezers

Riga, , Latvia

URO Ltd.

Riga, , Latvia

P. Stradins Clinical University Hospital

Riga, , Latvia

Vidzemes Hospital

Valmiera, , Latvia

The Hospital of Lithuanian University of Health SciencesLUHS

Kaunas, , Lithuania

PI Klaipedos University Hospital

Klaipėda, , Lithuania

National Cancer Institute

Vilnius, , Lithuania

Vilnius University Hospital Santaros Klinikos

Vilnius, , Lithuania

Canterbury Urology Research Trust

Christchurch, Canterbury, New Zealand

Waikato Hospital

Hamilton, , New Zealand

Tauranga Urology Research Limited

Tauranga, , New Zealand

Aliada

San Isidro, Lima region, Peru

Hospital Guillermo Almenara Irigoyen

Santiago de Surco, Lima region, Peru

Hospital Militar Luis Arias Schreiber

Lima, , Peru

Clínica El Golf

Lima, , Peru

Arkhangelsk Clinical Oncology Dispensary

Arkhangelsk, , Russia

Ltd "EVIMED"

Chelyabinsk, , Russia

Chelyabinsk Regional Oncology Dispensary

Chelyabinsk, , Russia

Ivanovo Regional Oncology Dispensary

Ivanovo, , Russia

Republican Clinical Oncology Dispensary Kazan

Kazan', , Russia

Research Centre of X-ray and Radiology

Moscow, , Russia

Volga District Med Center FMBA

Nizhny Novgorod, , Russia

LLC Reafan

Novosibirsk, , Russia

Medical Center "Avicenna"

Novosibirsk, , Russia

Clinical Oncological Dispensary of Omsk Region

Omsk, , Russia

AV Medical Group

Saint Petersburg, , Russia

Russian Scientific Radiology and Surgery Technologies Center

Saint Petersburg, , Russia

Scientific Research Instutute of Oncology n.a. N.N. Petrov

Saint Petersburg, , Russia

Multi-Field Clinical Medical Center "Medical City"

Tyumen, , Russia

Republican Clinical Oncology Dispensary

Ufa, , Russia

Vologda Regional Hospital

Vologda, , Russia

Sverdlovsk Regional Clinical Hospital #1

Yekaterinburg, , Russia

Cancercare Langenhoven

Port Elizabeth, Eastern Cape, South Africa

East Rand Medical Research Unit

Johannesburg, Gauteng, South Africa

University of Pretoria, Clinical Research Unit

Pretoria, Gauteng, South Africa

Cape Town Oncology Trials

Cape Town, , South Africa

Hospital Universitario Fundacion Alcorcon | Urologia

Alcorcón, Madrid, Spain

Fundacio Puigvert | Urologia

Barcelona, , Spain

Parc Tauli Hospital Universitari | Oncologia

Barcelona, , Spain

Hospital San Pedro De Alcantara | Oncologia

Cáceres, , Spain

Hospital Universitario Virgen De La Victoria | Urologia

Málaga, , Spain

Hospital Universitario Virgen Del Rocio S.L. | Urologia

Seville, , Spain

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, Kaohsiung, Taiwan

Changhua Christian Hospital

Changhua, , Taiwan

Taichung Veterans General Hospital

Taichung, , Taiwan

National Cheng Kung University Hospital

Tainan, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

CNE "Clinical Center of Oncology, Hematology, Transplantology and Palliative Care of the Cherkasy Regional Council"

Cherkasy, , Ukraine

City Dnipropetrovsk Multi- field Clinical Hosp. 4 DSMA

Dnipro, , Ukraine

Kyiv City Hospital #3 - Department of Urology

Kyiv, , Ukraine

Kyiv Regional Oncological Dispensary

Kyiv, , Ukraine

Countries

Australia; Brazil; Canada; Chile; China; India; Latvia; Lithuania; New Zealand; Peru; Russia; South Africa; Spain; Taiwan; Ukraine

References

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.

Reference Type: DERIVED

PMID: 39279580 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://clinicaltrials.bayer.com/study/21140

Click here to find further information and, after study completion, the study results according to Bayer's transparency standards

Other Identifiers

2022-502244-12-00

Identifier Type: OTHER

Identifier Source: secondary_id

2020-003093-48

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

21140

Identifier Type: -

Identifier Source: org_study_id