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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Prostatic Neoplasms
• Intervention / Treatment: Drug: Darolutamide (Nubeqa, BAY1841788); Other: Androgen deprivation therapy (ADT); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 662
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Heidelberg, Australia
    • Austin Health
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • Northern Cancer Institute
    • Sydney, New South Wales, Australia, 2751
      • Nepean Hospital
    • Sydney, New South Wales, Australia, 2109
      • Macquarie University Hospital
  • South Australia
    • South Terrace, South Australia, Australia, 5000
      • Cancer Research South Australia
  • Victoria
    • Frankston, Victoria, Australia, 3199
      • Peninsula Oncology Centre
• Brazil
  • Rio de Janeiro, Brazil, 22793-080
    • Instituto COI de Educação e Pesquisa
  • Bahia
    • Salvador, Bahia, Brazil, 41950-610
      • Assistência Multidisciplinar em Oncologia (AMO)
  • Goiás
    • Goiânia, Goiás, Brazil, 74605-070
      • Hosp. Araujo Jorge da Associação de Combate ao Câncer
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30130-100
      • Hospital da Universidade Federal de Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30150-270
      • Cetus Oncologia Hospital Dia
  • Parana
    • Curitiba, Parana, 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
    • Pelotas, Rio Grande Do Sul, Brazil, 96020-080
      • Unidade de Pesquisas Clinicas em Oncologia
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90880-480
      • Hospital Mae de Deus
    • Porto Alegre, Rio Grande Do Sul, Brazil, 91350-200
      • Hospital Nossa Senhora da Conceicao
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90020-090
      • Irmandade Santa Casa de Misericordia de Porto Alegre
  • Sao Paulo
    • Barretos/SP, Sao Paulo, Brazil, 14784-400
      • Fundacao Pio XII Hospital de Cancer de Barretos
    • São José do Rio Preto, Sao Paulo, Brazil, 15090-000
      • Hospital de Base | Integrated Research Center
    • São Paulo, Sao Paulo, Brazil, 01243-020
      • Urobrasil
    • São Paulo, Sao Paulo, Brazil, 04039-004
      • Inst. de Assistência Médica ao Sérvidor Público Estadual
    • São Paulo, Sao Paulo, Brazil, 03102-002
      • IBCC - Instituto Brasileiro de Controle do Cancer
• Canada
  • Ontario
    • Burlington, Ontario, Canada, L7N 3V2
      • G. Kenneth Jansz Medicine Professional Corporation
  • Quebec
    • Montreal, Quebec, Canada, H2X 0A9
      • Centre de Recherche du CHUM
• Chile
  • Santiago, Chile, 7500921
    • Fundacion Arturo Lopez Perez
  • Santiago, Chile, 7510032
    • Oncovida
  • Santiago, Chile, 8330024
    • Hospital Clínico de la Pontificia Univ. Católica de Chile
  • Santiago, Chile
    • UROMED
  • Araucanía
    • Temuco, Araucanía, Chile, 4781156
      • Centro de Investigacion Clinica del Sur
  • Santiago
    • Providencia, Santiago, Chile, 7500653
      • Centro de Estudios Clínicos SAGA SpA
  • Valparaíso
    • Viña del Mar, Valparaíso, Chile, 2520598
      • OncoCentro
• China
  • Beijing, China, 100142
    • Beijing Cancer Hospital
  • Beijing, China, 100083
    • Peking University Third Hospital
  • Beijing, China, 100730
    • Beijing Hospital
  • Beijing, China, 100000
    • Cancer Hospital, Chinese Academy of Medical Sciences
  • Anhui
    • Hefei City, Anhui Province, Anhui, China, 230031
      • Anhui Provincial Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Sun Yat-Sen University Cancer Center
    • Guangzhou, Guangdong, China, 510180
      • Guangzhou First People Hospital
    • Shenzhen, Guangdong, China, 518172
      • Cancer hospital Chinese Academy of Medical Sciences, Shenzhen Center
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Hosp. of Tongji Med Coll, Huazhong Uni of Sci & Tech.
    • Wuhan, Hubei, China, 430071
      • Zhongnan Hospital of Wuhan University
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer hospital
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • NJ Drum Tower Hospital, the Affil Hos of NJ Univ Med School
    • Nantong, Jiangsu, China, 226361
      • Nantong Tumor Hospital
    • Suzhou, Jiangsu, China, 215004
      • The 2nd Affiliated Hospital of Soochow University
  • Jilin
    • Changchun, Jilin, China, 130021
      • 1st Hospital of Jilin University
  • Liaoning
    • Shengyang, Liaoning, China, 110042
      • Liaoning Cancer Hospital and Institute
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • The First Affiliated Hospital of Xi'an Jiaotong University
  • Shandong
    • Yantai, Shandong, China, 264000
      • Yantai Yuhuangding Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610072
      • SichuanAcademyofMedicalSciences&SichuanProvincialPeople'sHos
    • Chengdu, Sichuan, China
      • Sichuan University West China Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310014
      • Zhejiang Provincial People's Hospital
    • Hangzhou, Zhejiang, China, 310000
      • The 1st Affiliated Hospital of Zhejiang University
    • Ningbo, Zhejiang, China, 315010
      • Ningbo First Hospital
    • Wenzhou, Zhejiang, China, 325000
      • The First Affiliated Hospital of Wenzhou Medical University
• India
  • Kolkata, India, 700156
    • Tata Medical Center
  • Nashik, India, 422009
    • Apex Wellness Hospital
  • New Delhi, India, 110 085
    • Rajiv Gandhi Cancer Institute & Research Centre
  • Andhra Pradesh
    • Vishakapatnam, Andhra Pradesh, India, 530017
      • Mahatma Gandhi Cancer Hospital & Research Institute
  • Delhi
    • Bhubaneswar, Delhi, India, 751019
      • All India Institute of Medical Sciences
  • Gujarat
    • Ahmedabad, Gujarat, India, 380016
      • The Gujarat Cancer & Research Institute
    • Ahmedabad, Gujarat, India, 380060
      • HCG Cancer Centre - Ahmedabad
    • Vadodara, Gujarat, India, 390007
      • Cancer Care Clinic - Vadodara
  • Karnataka
    • Belgaum, Karnataka, India, 590010
      • K.L.E.S. Dr. Prabhakar Kore Hospital & Medical Research Centre
    • Bengaluru, Karnataka, India, 560027
      • Healthcare Global Enterprises Ltd
  • Kerala
    • Kochi, Kerala, India, 682026
      • Amrita Institute of Medical Sciences
    • Thiruvananthapuram, Kerala, India, 695011
      • Regional Cancer Centre - Thiruvananthapuram
  • Maharashtra
    • Aurangabad, Maharashtra, India, 431001
      • Marathwada Regional Cancer Centre and Research Institute
    • Mumbai, Maharashtra, India, 400 026
      • Jaslok Hospital and Research Centre
    • Nashik, Maharashtra, India, 422004
      • Curie Manavata Cancer Centre
    • Pune, Maharashtra, India, 411001
      • Jehangir Hospital
  • Orissa
    • Bhubaneswar, Orissa, India, 751007
      • Sparsh Hospital & Critical Care
  • Pondicherry
    • Gorimedu, Pondicherry, India, 605006
      • Jawaharlal Institute Of Postgraduate Medical Education and R
  • Punjab
    • Chandigarh, Punjab, India, 160012
      • Post Graduate Institute of Medical Education and Research
    • Ludhiana, Punjab, India, 141008
      • Christian Medical Center & Hospital
  • Rajasthan
    • Jaipur, Rajasthan, India, 302017
      • Sawami Man Singh (SMS) Medical College & Attached Hospitals
  • Tamil N?du
    • Madurai, Tamil N?du, India, 625107
      • Meenakshi Mission Hospital & Research Centre
    • Madurai, Tamil N?du, India, 625020
      • Apollo Speciality Hospitals
• Latvia
  • Daugavpils, Latvia, LV-5417
    • Daugavpils Regional Hospital
  • Riga, Latvia, LV-1002
    • P. Stradins Clinical University Hospital
  • Riga, Latvia, 1038
    • RAKUS Hospital Gailezers
  • Riga, Latvia, LV-1001
    • URO Ltd.
  • Valmiera, Latvia, LV-4201
    • Vidzemes Hospital
• Lithuania
  • Kaunas, Lithuania, LT-50009
    • The Hospital of Lithuanian University of Health SciencesLUHS
  • Klaipeda, Lithuania, LT-92288
    • PI Klaipedos University Hospital
  • Vilnius, Lithuania, LT-08660
    • National Cancer Institute
  • Vilnius, Lithuania, LT-08661
    • Vilnius University hospital Santaros klinikos
• New Zealand
  • Christchurch, New Zealand, 8013
    • Canterbury Urology Research Trust
  • Hamilton, New Zealand, 3200
    • Waikato Hospital
  • Hamilton, New Zealand, 3204
    • Waikato Hospital
  • Tauranga, New Zealand, 3112
    • Tauranga Urology Research Limited
• Peru
  • Lima, Peru, LIMA 11
    • Hospital Militar Luis Arias Schreiber
  • Lima, Peru, LIMA 27
    • Clínica El Golf
  • Lima
    • San Isidro, Lima, Peru, 15036
      • Aliada
    • Santiago de Surco, Lima, Peru, 15033
      • Hospital Guillermo Almenara Irigoyen
• Russian Federation
  • Arkhangelsk, Russian Federation, 163045
    • Arkhangelsk Clinical Oncology Dispensary
  • Chelyabinsk, Russian Federation, 454048
    • Ltd "EVIMED"
  • Chelyabinsk, Russian Federation, 454087
    • Chelyabinsk Regional Oncology Dispensary
  • Ivanovo, Russian Federation, 153040
    • Ivanovo Regional Oncology Dispensary
  • Kazan, Russian Federation, 420029
    • Republican Clinical Oncology Dispensary Kazan
  • Moscow, Russian Federation, 117997
    • Research Centre of X-ray and Radiology
  • Nizhny Novgorod, Russian Federation, 603109
    • Volga District Med Center FMBA
  • Novosibirsk, Russian Federation, 630007
    • Medical Center "Avicenna"
  • Novosibirsk, Russian Federation, 630099
    • LLC Reafan
  • Omsk, Russian Federation, 644013
    • Clinical Oncological Dispensary of Omsk Region
  • St. Petersburg, Russian Federation, 197758
    • Russian Scientific Radiology and Surgery Technologies Center
  • St. Petersburg, Russian Federation, 197758
    • Scientific Research Instutute of Oncology n.a. N.N. Petrov
  • St. Petersburg, Russian Federation, 196006
    • AV Medical Group
  • Tyumen, Russian Federation, 625041
    • Multi-Field Clinical Medical Center "Medical City"
  • Ufa, Russian Federation, 450054
    • Republican Clinical Oncology Dispensary Ufa
  • Vologda, Russian Federation, 160022
    • Vologda Regional Hospital
  • Yekaterinburg, Russian Federation, 620102
    • Sverdlovsk Regional Clinical Hospital #1
• South Africa
  • Cape Town, South Africa, 7570
    • Cape Town Oncology Trials
  • Eastern Cape
    • Port Elizabeth, Eastern Cape, South Africa, 6045
      • Cancercare Langenhoven
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 1475
      • East Rand Medical Research Unit
    • Pretoria, Gauteng, South Africa, 0002
      • University of Pretoria, Clinical Research Unit
• Spain
  • Barcelona, Spain, 08025
    • Hospital Fundació Puigvert
  • Cáceres, Spain, 10003
    • Hospital San Pedro de Alcántara
  • Málaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria | Cardiology Department
  • Sevilla, Spain, 41013
    • H Virgen del Rocio |Cardiology|AF|Stroke prevention
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Corporació Sanitària Parc Taulí
  • Madrid
    • Alcorcón, Madrid, Spain, 28922
      • Fundación Hospital Alcorcón
• Taiwan
  • Changhua, Taiwan, 50006
    • Changhua Christian Hospital
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Kaohsiung
    • Kaohsiung City, Kaohsiung, Taiwan, 807377
      • Kaohsiung Medical University Chung-Ho Memorial Hospital
• Ukraine
  • Dnipro, Ukraine, 49102
    • City Dnipropetrovsk Multi- field Clinical Hosp. 4 DSMA
  • Kyiv, Ukraine, 02660
    • Kyiv City Hospital #3
  • Kyiv, Ukraine, 4107
    • Kyiv Regional Oncological Dispensary
  • Zaporizhia, Ukraine, 69600
    • CNE "Clinical Center of Oncology, Hematology, Transplantology and Palliative Care of the Cherkasy Regional Council"

Participation Criteria

Eligibility Criteria

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

Description

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

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 600 mg (2 tablets of 300 mg) twice daily with food and ADT of investigator's choice as standard therapy	Drug: Darolutamide (Nubeqa, BAY1841788); Coated tablet, oral administration; Other: Androgen deprivation therapy (ADT); Luteinizing hormone-releasing hormone (LHRH) agonist/antagonists or orchiectomy
Placebo Comparator: Placebo+ADT; Participants will receive placebo twice daily with food and ADT of investigator's choice as standard therapy	Other: Androgen deprivation therapy (ADT); Luteinizing hormone-releasing hormone (LHRH) agonist/antagonists or orchiectomy; Drug: Placebo; Coated tablet matching Darolutamide in appearance, oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiological progression-free survival (rPFS)	Time from the date of randomization to the date of first documentation of radiological progressive disease or death due to any cause, whichever occurs first.	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Time from the date of randomization to the date of death from any cause.	Up to 55 months
Time to castration-resistant prostate cancer (CRPC)	Time from the date of randomization to the date of first castration resistant event (radiological progression, PSA progression or symptomatic skeletal events, whichever occurs first).	Up to 55 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.	Up to 55 months
Time to PSA progression	Time from the date of randomization to the date of first prostate-specific antigen (PSA) progression. PSA progression is defined as a ≥25% increase above the nadir (lowest Screening or baseline) value, which is confirmed by a second value 3 or more weeks later, and an increase in absolute value of ≥ 2 ng/mL above nadir, at least 12 weeks from baseline.	Up to 55 months
PSA undetectable rates (<0.2 ng/mL)	The percentage of participants with detectable PSA values (≥0.2 ng/mL) at baseline which become undetectable (<0.2 ng/mL) during the study treatment.	Up to 55 months
Time to pain progression	Time from the date of randomization to pain progression, where progression is defined as an increase of 2 or more points from baseline. Pain to be assessed with a patient reported questionaire.	Up to 55 months
Number of participants with adverse events as a measure of safety		Up to 55 months

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Orion Corporation, Orion Pharma

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2021
• Primary Completion (Estimated): June 7, 2024
• Study Completion (Estimated): September 26, 2025

Study Registration Dates

• First Submitted: January 29, 2021
• First Submitted That Met QC Criteria: January 29, 2021
• First Posted (Actual): February 3, 2021

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 19, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Metastatic hormone-sensitive prostate cancer
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Hypersensitivity; Prostatic Neoplasms; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Androgens
• Other Study ID Numbers: 21140; 2020-003093-48 (EudraCT Number); 2022-502244-12-00 (Other 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 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No