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

Prostatic Neoplasms Clinical Trial

— ARANOTE  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04736199
• Other study ID #: 21140
• Secondary ID: 2022-502244-12-0
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 23, 2021
• Est. completion date: September 26, 2025

Study information

• Verified date: June 2024
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 662
• Est. completion date: September 26, 2025
• Est. primary completion date: June 7, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hypersensitivity
• Prostatic Neoplasms

Intervention

Drug:
• Darolutamide (Nubeqa, BAY1841788)
Coated tablet, oral administration
• Placebo
Coated tablet matching Darolutamide in appearance, oral administration

Other:
• Androgen deprivation therapy (ADT)
Luteinizing hormone-releasing hormone (LHRH) agonist/antagonists or orchiectomy

Locations

Country	Name	City	State
Australia	Peninsula Oncology Centre	Frankston	Victoria
Australia	Austin Health	Heidelberg
Australia	Cancer Research South Australia	South Terrace	South Australia
Australia	Northern Cancer Institute	St Leonards	New South Wales
Australia	Macquarie University Hospital	Sydney	New South Wales
Australia	Nepean Hospital	Sydney	New South Wales
Brazil	Fundacao Pio XII Hospital de Cancer de Barretos	Barretos/SP	Sao Paulo
Brazil	Cetus Oncologia Hospital Dia	Belo Horizonte	Minas Gerais
Brazil	Hospital da Universidade Federal de Minas Gerais	Belo Horizonte	Minas Gerais
Brazil	Liga Paranaense de Combate ao Cancer-Hosp Erasto Gaertner	Curitiba	Parana
Brazil	Hosp. Araujo Jorge da Associação de Combate ao Câncer	Goiânia	Goiás
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	FZ Pesquisa e Servicos em Cardiologia | Porto Alegre, Brazil	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital Mae de Deus	Porto Alegre	Rio Grande Do Sul
Brazil	Irmandade da Santa Casa de Misericordia de Porto Alegre | Hospital Sao Francisco - Centro Medico Pesquisa Clinica Cardiologia	Porto Alegre	Rio Grande Do Sul
Brazil	Instituto COI de Educação e Pesquisa	Rio de Janeiro
Brazil	Assistência Multidisciplinar em Oncologia (AMO)	Salvador	Bahia
Brazil	Hospital de Base | Integrated Research Center	São José do Rio Preto	Sao Paulo
Brazil	IBCC - Instituto Brasileiro de Controle do Cancer	São Paulo	Sao Paulo
Brazil	Inst. de Assistência Médica ao Sérvidor Público Estadual	São Paulo	Sao Paulo
Brazil	Urobrasil	São Paulo	Sao Paulo
Canada	G. Kenneth Jansz Medicine Professional Corporation	Burlington	Ontario
Canada	Centre de Recherche du CHUM	Montreal	Quebec
Chile	Centro de Estudios Clínicos SAGA SpA	Providencia	Santiago
Chile	Fundación Arturo López Perez	Santiago
Chile	Hospital Clínico de la Pontificia Univ. Católica de Chile	Santiago
Chile	Oncovida	Santiago
Chile	UROMED	Santiago
Chile	Centro de Investigación Clínica del Sur	Temuco	Araucanía
Chile	OncoCentro	Viña del Mar	Valparaíso
China	Beijing Cancer Hospital	Beijing
China	Beijing Hospital	Beijing
China	Cancer Hospital, Chinese Academy of Medical Sciences	Beijing
China	Peking University Third Hospital	Beijing
China	1st Hospital of Jilin University	Changchun	Jilin
China	Hunan Cancer Hospital	Changsha	Hunan
China	Sichuan University West China Hospital	Chengdu	Sichuan
China	SichuanAcademyofMedicalSciences&SichuanProvincialPeople'sHos	Chengdu	Sichuan
China	Guangzhou First People Hospital	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	The 1st Affiliated Hospital of Zhejiang University	Hangzhou	Zhejiang
China	ZheJiang Provincial People's Hospital	Hangzhou	Zhejiang
China	Anhui Provincial Hospital	Hefei City, Anhui Province	Anhui
China	NJ Drum Tower Hospital, the Affil Hos of NJ Univ Med School	Nanjing	Jiangsu
China	Nantong tumor hospital	Nantong	Jiangsu
China	Ningbo First Hospital	Ningbo	Zhejiang
China	Liaoning Cancer Hospital and Institute	Shengyang	Liaoning
China	Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center	Shenzhen	Guangdong
China	The 2nd Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang
China	Hubei Cancer Hospital	Wuhan	Hubei
China	Tongji Hosp. of Tongji Med Coll, Huazhong Uni of Sci & Tech.	Wuhan	Hubei
China	Zhongnan hospital ,Wuhan University	Wuhan	Hubei
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shaanxi
China	Yantai Yuhuangding Hospital	Yantai	Shandong
India	HCG Cancer Centre - Ahmedabad	Ahmedabad	Gujarat
India	The Gujarat Cancer & Research Institute	Ahmedabad	Gujarat
India	Marathwada Regional Cancer Centre and Research Institute	Aurangabad	Maharashtra
India	K.L.E.S. Dr. Prabhakar Kore Hospital & Medical Research Centre	Belgaum	Karnataka
India	Healthcare Global Enterprises Ltd	Bengaluru	Karnataka
India	All India Institute of Medical Sciences	Bhubaneswar	Delhi
India	Sparsh Hospital & Critical Care	Bhubaneswar	Orissa
India	Post Graduate Institute of Medical Education and Research	Chandigarh	Punjab
India	Jawaharlal Institute Of Postgraduate Medical Education and R	Gorimedu	Pondicherry
India	Sawami Man Singh (SMS) Medical College & Attached Hospitals	Jaipur	Rajasthan
India	Amrita Institute of Medical Sciences	Kochi	Kerala
India	Tata Medical Center	Kolkata
India	Christian Medical Center & Hospital	Ludhiana	Punjab
India	Apollo Speciality Hospitals	Madurai	Tamil N?du
India	Meenakshi Mission Hospital & Research Centre	Madurai	Tamil N?du
India	Jaslok Hospital and Research Centre	Mumbai	Maharashtra
India	Apex Wellness Hospital	Nashik
India	Curie Manavata Cancer Centre	Nashik	Maharashtra
India	Rajiv Gandhi Cancer Institute & Research Centre	New Delhi
India	Jehangir Hospital	Pune	Maharashtra
India	Regional Cancer Centre - Thiruvananthapuram	Thiruvananthapuram	Kerala
India	Cancer Care Clinic - Vadodara	Vadodara	Gujarat
India	Mahatma Gandhi Cancer Hospital & Research Institute	Vishakapatnam	Andhra Pradesh
Latvia	Daugavpils Regional Hospital	Daugavpils
Latvia	P. Stradins Clinical University Hospital	Riga
Latvia	RAKUS Hospital Gailezers	Riga
Latvia	URO Ltd.	Riga
Latvia	Vidzemes Hospital	Valmiera
Lithuania	The Hospital of Lithuanian University of Health SciencesLUHS	Kaunas
Lithuania	PI Klaipedos University Hospital	Klaipeda
Lithuania	National Cancer Institute	Vilnius
Lithuania	Vilnius University Hospital Santaros Klinikos	Vilnius
New Zealand	Canterbury Urology Research Trust	Christchurch
New Zealand	Waikato Hospital	Hamilton
New Zealand	Waikato Hospital	Hamilton
New Zealand	Tauranga Urology Research Limited	Tauranga
Peru	Clínica El Golf	Lima
Peru	Hospital Militar Luis Arias Schreiber	Lima
Peru	Aliada	San Isidro	Lima
Peru	Hospital Guillermo Almenara Irigoyen	Santiago de Surco	Lima
Russian Federation	Arkhangelsk Clinical Oncology Dispensary	Arkhangelsk
Russian Federation	Chelyabinsk Regional Oncology Dispensary	Chelyabinsk
Russian Federation	Ltd "EVIMED"	Chelyabinsk
Russian Federation	Ivanovo Regional Oncology Dispensary	Ivanovo
Russian Federation	Republican Clinical Oncology Dispensary Kazan	Kazan
Russian Federation	Research Centre of X-ray and Radiology	Moscow
Russian Federation	Volga District Med Center FMBA	Nizhny Novgorod
Russian Federation	LLC Reafan	Novosibirsk
Russian Federation	Medical Center "Avicenna"	Novosibirsk
Russian Federation	Clinical Oncological Dispensary of Omsk Region	Omsk
Russian Federation	AV Medical Group	St. Petersburg
Russian Federation	Russian Scientific Radiology and Surgery Technologies Center	St. Petersburg
Russian Federation	Scientific Research Instutute of Oncology n.a. N.N. Petrov	St. Petersburg
Russian Federation	Multi-Field Clinical Medical Center "Medical City"	Tyumen
Russian Federation	Republican Clinical Oncology Dispensary Ufa	Ufa
Russian Federation	Vologda Regional Hospital	Vologda
Russian Federation	Sverdlovsk Regional Clinical Hospital #1	Yekaterinburg
South Africa	Cape Town Oncology Trials	Cape Town
South Africa	East Rand Medical Research Unit	Johannesburg	Gauteng
South Africa	Cancercare Langenhoven	Port Elizabeth	Eastern Cape
South Africa	University of Pretoria, Clinical Research Unit	Pretoria	Gauteng
Spain	Fundación Hospital Alcorcón	Alcorcón	Madrid
Spain	Hospital Fundació Puigvert	Barcelona
Spain	Hospital San Pedro de Alcántara	Cáceres
Spain	Hospital Universitario Virgen de la Victoria | Cardiology Department	Málaga
Spain	Corporació Sanitària Parc Taulí	Sabadell	Barcelona
Spain	H Virgen del Rocio |Cardiology|AF|Stroke prevention	Sevilla
Taiwan	Changhua Christian Hospital	Changhua
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung City	Kaohsiung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	Taipei Veterans General Hospital	Taipei
Ukraine	City Dnipropetrovsk Multi- field Clinical Hosp. 4 DSMA	Dnipro
Ukraine	Kyiv City Hospital #3	Kyiv
Ukraine	Kyiv Regional Oncological Dispensary	Kyiv
Ukraine	CNE "Clinical Center of Oncology, Hematology, Transplantology and Palliative Care of the Cherkasy Regional Council"	Zaporizhia

Sponsors (2)

Lead Sponsor	Collaborator
Bayer	Orion Corporation, Orion Pharma

Countries where clinical trial is conducted

Australia,  Brazil,  Canada,  Chile,  China,  India,  Latvia,  Lithuania,  New Zealand,  Peru,  Russian Federation,  South Africa,  Spain,  Taiwan,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall survival (OS)	Time from the date of randomization to the date of death from any cause.	Up to 55 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Number of participants with adverse events as a measure of safety		Up to 55 months

External Links

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