Darolutamide in Addition to Standard Androgen Deprivation Therapy and Docetaxel in Metastatic Hormone-Sensitive Prostate Cancer (ARASENS)

A Randomized, Double-blind, Placebo Controlled Phase III Study of Darolutamide (ODM-201) Versus Placebo in Addition to Standard Androgen Deprivation Therapy and Docetaxel in Patients With Metastatic Hormone Sensitive Prostate Cancer

The purpose of the study is to assess the efficacy and safety of BAY1841788 (darolutamide (ODM-201)) in combination with standard androgen deprivation therapy (ADT) and docetaxel in patients with metastatic hormone sensitive prostate cancer.

Study Overview

• Status: Completed
• Conditions: Metastatic Hormone-sensitive Prostate Cancer
• Intervention / Treatment: Drug: BAY1841788 / darolutamide (ODM-201); Drug: Standard ADT (androgen deprivation therapy); Drug: Docetaxel; Drug: Placebo

Detailed Description

This is a randomized, double-blind, placebo-controlled, multicenter phase III study. The study population will consist of approximately 1300 subjects with metastatic hormone sensitive prostate cancer (mHSPC), who will be randomized (1:1 ratio) to receive 600 mg (2 x 300 mg tablets) of darolutamide (ODM-201)/placebo twice daily with food, equivalent to a total daily dose of 1200 mg, in addition to standard androgen deprivation therapy (ADT) and docetaxel. Subjects will be stratified at randomization for the extent of disease and for Alkaline Phosphatase levels. All subjects will be treated with ADT as standard therapy. Six cycles of docetaxel will be administered after randomization.

The subjects considered for inclusion in the study will have metastatic prostate cancer and will be candidates for ADT and docetaxel.

Treatment with darolutamide (ODM-201)/placebo will be administered until symptomatic progressive disease, change of antineoplastic therapy, unacceptable toxicity, until subject withdraws consent, withdrawal from the study at the discretion of the investigator or his/her designated associate(s), death, non-compliance, or if sponsor terminates the study.

• Study Type: Interventional
• Enrollment (Actual): 1306
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
    • Sydney, New South Wales, Australia, 2010
  • South Australia
    • Adelaide, South Australia, Australia, 5000
    • Kurralta Park, South Australia, Australia, 5037
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
• Belgium
  • Brussels, Belgium, 1070
  • Bruxelles - Brussel, Belgium, 1200
  • Bruxelles - Brussel, Belgium, 1000
  • Charleroi, Belgium, 6000
  • Gent, Belgium, 9000
  • Namur, Belgium, 5000
  • Antwerpen
    • Wilrijk, Antwerpen, Belgium, 2610
• Brazil
  • Rio de Janeiro, Brazil, 20231-050
  • Rio de Janeiro, Brazil, 22793-080
  • Bahia
    • Salvador, Bahia, Brazil, 41253-190
  • Espírito Santo
    • Cachoeiro de Itapemirim, Espírito Santo, Brazil, 29308-020
  • Parana
    • Curitiba, Parana, Brazil, 81520-060
  • Rio Grande Do Norte
    • Natal, Rio Grande Do Norte, Brazil, 59062-000
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90050 170
  • Sao Paulo
    • Santo André, Sao Paulo, Brazil, 09060-650
    • São Paulo, Sao Paulo, Brazil, 04014-002
• Bulgaria
  • Gabrovo, Bulgaria, 5300
  • Pleven, Bulgaria, 5809
  • Sofia, Bulgaria, 1784
  • Sofia, Bulgaria, 1431
  • Sofia, Bulgaria, 1303
  • Varna, Bulgaria, 9010
  • Vratsa, Bulgaria, 3000
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
    • Edmonton, Alberta, Canada, T6G 1Z2
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
    • Toronto, Ontario, Canada, M4N 3M5
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
• China
  • Beijing, China, 100050
  • Beijing, China, 100730
  • Beijing, China, 100083
  • Beijing, China, 100142
  • Beijing, China, 100034
  • Chongqing, China, 400030
  • Shanghai, China, 200032
  • Shanghai, China, 200040
  • Shanghai, China, 200080
  • Shanghai, China, 200000
  • Shanghai, China, 200092
  • Shanghai, China, 200072
  • Tianjin, China, 300000
  • Tianjin, China, 300052
  • Anhui
    • Hefei City, Anhui Province, Anhui, China, 230031
  • Fujian
    • Xiamen, Fujian, China, 361003
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
  • Henan
    • Zhengzhou, Henan, China, 450000
  • Hubei
    • Wuhan, Hubei, China, 430030
    • Wuhan, Hubei, China, 430079
  • Hunan
    • Changsha, Hunan, China, 410013
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
    • Nanjing, Jiangsu, China, 210000
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
  • Jilin
    • Changchun City, Jilin, China, 130061
  • Liaoning
    • Shengyang, Liaoning, China, 110042
    • Shenyang, Liaoning, China, 110001
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
  • Shandong
    • Jinan, Shandong, China, 250012
    • Jinan, Shandong, China, 250021
    • Yantai, Shandong, China, 264000
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
    • Hangzhou, Zhejiang, China, 310014
    • Wenzhou, Zhejiang, China, 325000
• Czechia
  • Brno, Czechia, 656 91
  • Brno, Czechia, 602 00
  • Praha 10, Czechia, 10034
  • Praha 2, Czechia, 128 08
  • Praha 2, Czechia, 120 00
  • Praha 5, Czechia, 150 06
  • Praha 8, Czechia, 180 81
• Finland
  • Helsinki, Finland, 00290
  • Jyväskylä, Finland, 40620
  • Kuopio, Finland, 70210
  • Mikkeli, Finland, FIN-50100
  • Oulu, Finland, 90220
  • Tampere, Finland, 33521
  • Turku, Finland, 20520
• France
  • Angers Cedex, France, 49055
  • Besancon, France, 25030
  • Bordeaux Cedex, France, 33076
  • Brest, France, 29200
  • Cergy Pontoise, France, 95303
  • Clermont-ferrand, France, 63011
  • Creteil, France, 94010
  • Marseille, France, 13273
  • Montpellier Cedex, France, 34298
  • Nancy, France, 54100
  • Pierre Benite, France, 69495
  • Poitiers, France, 86021
  • Reims, France, 51726
  • Saint Herblain Cedex, France, 44805
  • Saint-gregoire, France, 35760
  • Strasbourg, France, 67033
  • Villejuif Cedex, France, 94805
• Germany
  • Berlin, Germany, 12203
  • Baden-Württemberg
    • Freiburg, Baden-Württemberg, Germany, 79106
    • Nürtingen, Baden-Württemberg, Germany, 72622
    • Tübingen, Baden-Württemberg, Germany, 72076
    • Ulm, Baden-Württemberg, Germany, 89075
  • Bayern
    • Erlangen, Bayern, Germany, 91054
  • Mecklenburg-Vorpommern
    • Rostock, Mecklenburg-Vorpommern, Germany, 18107
  • Niedersachsen
    • Braunschweig, Niedersachsen, Germany, 38126
  • Nordrhein-Westfalen
    • Münster, Nordrhein-Westfalen, Germany, 48149
  • Sachsen-Anhalt
    • Magdeburg, Sachsen-Anhalt, Germany, 39120
  • Thüringen
    • Jena, Thüringen, Germany, 07747
• Israel
  • Beer Sheva, Israel, 8410101
  • Haifa, Israel, 3109601
  • Holon, Israel, 5822012
  • Jerusalem, Israel, 9112001
  • Petach Tikva, Israel, 4941492
  • Tel Aviv, Israel, 6423906
  • Zefat, Israel, 1311001
  • Zrifin, Israel, 7030000
• Italy
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
    • Parma, Emilia-Romagna, Italy, 43126
  • Lazio
    • Roma, Lazio, Italy, 00152
  • Lombardia
    • Milano, Lombardia, Italy, 20141
  • Piemonte
    • Novara, Piemonte, Italy, 28100
    • Torino, Piemonte, Italy, 10043
  • Trentino-Alto Adige
    • Trento, Trentino-Alto Adige, Italy, 38100
  • Veneto
    • Padova, Veneto, Italy, 35128
    • Verona, Veneto, Italy, 37134
• Japan
  • Chiba, Japan, 260-8677
  • Chiba, Japan, 260-8717
  • Fukuoka, Japan, 811-1395
  • Gifu, Japan, 500-8717
  • Kumamoto, Japan, 860-0008
  • Miyazaki, Japan, 889-1692
  • Nagasaki, Japan, 852-8501
  • Okayama, Japan, 700-8558
  • Osaka, Japan, 545-8586
  • Osaka, Japan, 541-8567
  • Tokushima, Japan, 770-8503
  • Wakayama, Japan, 641-8510
  • Aichi
    • Nagoya, Aichi, Japan, 466-8560
  • Aomori
    • Hirosaki, Aomori, Japan, 036-8563
  • Chiba
    • Asahi, Chiba, Japan, 289-2511
    • Kashiwa, Chiba, Japan, 277-8577
    • Sakura, Chiba, Japan, 285-8741
  • Ehime
    • Matsuyama, Ehime, Japan, 791-0280
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 003-0804
  • Hyogo
    • Kobe, Hyogo, Japan, 650-0017
  • Ishikawa
    • Kanazawa, Ishikawa, Japan, 920-8641
    • Kanazawa, Ishikawa, Japan, 920-8530
  • Kagawa
    • Kita, Kagawa, Japan, 761-0793
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 232-0024
    • Yokohama, Kanagawa, Japan, 241-8515
  • Mie
    • Tsu, Mie, Japan, 514-8507
  • Miyagi
    • Sendai, Miyagi, Japan, 980-8574
  • Nara
    • Kashihara, Nara, Japan, 634-8522
  • Osaka
    • Osakasayama, Osaka, Japan, 589-8511
    • Suita, Osaka, Japan, 565-0871
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan, 431-3192
  • Tochigi
    • Shimotsuke, Tochigi, Japan, 329-0498
    • Utsunomiya, Tochigi, Japan, 321-0974
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8655
    • Bunkyo-ku, Tokyo, Japan, 113-8603
    • Bunkyo-ku, Tokyo, Japan, 113-8431
    • Koto-ku, Tokyo, Japan, 135-8550
    • Meguro-ku, Tokyo, Japan, 152-8902
    • Minato-ku, Tokyo, Japan, 105-8471
    • Mitaka, Tokyo, Japan, 181-8611
    • Nakano-ku, Tokyo, Japan, 164-8541
    • Shinjuku-ku, Tokyo, Japan, 160-8582
    • Shinjuku-ku, Tokyo, Japan, 162-8543
  • Tottori
    • Yonago, Tottori, Japan, 683-8504
  • Yamaguchi
    • Ube, Yamaguchi, Japan, 755-8505
• Korea, Republic of
  • Busan, Korea, Republic of, 47392
  • Daegu, Korea, Republic of, 700721
  • Gyeonggi-do, Korea, Republic of, 11923
  • Seoul, Korea, Republic of, 138-736
  • Seoul, Korea, Republic of, 02841
  • Seoul, Korea, Republic of, 03722
  • Seoul, Korea, Republic of, 06591
  • Seoul, Korea, Republic of, 6351
  • Gwangju Gwang''yeogsi
    • Gwangju, Gwangju Gwang''yeogsi, Korea, Republic of, 61469
  • Gyeonggido
    • Seongnam-si, Gyeonggido, Korea, Republic of, 13620
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 6273
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 3080
• Mexico
  • Distrito Federal
    • Ciudad de Mexico, Distrito Federal, Mexico, 06760
    • México, D. F., Distrito Federal, Mexico, 06760
  • Morelos
    • Cuernavaca, Morelos, Mexico, 62290
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64460
  • Querétaro
    • Santiago de Querétaro, Querétaro, Mexico, 76000
  • Sinaloa
    • Mazatlán, Sinaloa, Mexico, 82110
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
  • Amsterdam, Netherlands, 1066 CX
  • Den Haag, Netherlands, 2545 AA
  • Dordrecht, Netherlands, 3318 AT
  • Geleen, Netherlands, 6162 BG
  • Hilversum, Netherlands, 1213 XZ
  • Hoofddorp, Netherlands, 2134 TM
  • Tilburg, Netherlands, 5042 AD
• Poland
  • Lodz, Poland, 90-302
  • Lublin, Poland, 20-362
  • Rybnik, Poland, 44-200
  • Siedlce, Poland, 08-110
  • Waliszew, Poland, 05-135
  • Warszawa, Poland, 02-781
• Russian Federation
  • Barnaul, Russian Federation, 656045
  • Chelyabinsk, Russian Federation, 454048
  • Chelyabinsk, Russian Federation, 454087
  • Moscow, Russian Federation, 125284
  • Moscow, Russian Federation, 115478
  • Novosibirsk, Russian Federation, 630099
  • Omsk, Russian Federation, 644013
  • St. Petersburg, Russian Federation, 188663
  • St. Petersburg, Russian Federation, 194017
  • St. Petersburg, Russian Federation, 197136
• Spain
  • Barcelona, Spain, 08003
  • Barcelona, Spain, 08041
  • Barcelona, Spain, 08023
  • Barcelona, Spain, 8036
  • Cáceres, Spain, 10003
  • Córdoba, Spain, 14004
  • Lugo, Spain, 27003
  • Madrid, Spain, 28034
  • Madrid, Spain, 28041
  • Valencia, Spain, 46009
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
  • Illes Baleares
    • Palma De Mallorca, Illes Baleares, Spain, 7120
  • Málaga
    • Malaga, Málaga, Spain, 29010
• Sweden
  • Göteborg, Sweden, 413 45
  • Lund, Sweden, 221 85
  • Stockholm, Sweden, 17176
  • Umea, Sweden, 901 85
  • Uppsala, Sweden, 751 85
• Taiwan
  • Taichung, Taiwan, 40447
  • Taipei, Taiwan, 100
  • Taipei, Taiwan, 11217
  • Taoyuan, Taiwan, 33305
  • Kaohsiung
    • Kaohsiung City, Kaohsiung, Taiwan, 807377
• United Kingdom
  • Belfast, United Kingdom, BT9 7AB
  • Glasgow, United Kingdom, G12 0YN
  • London, United Kingdom, W6 8RF
  • London, United Kingdom, SW3 6JJ
  • London, United Kingdom, NW1 2BU
  • Essex
    • Colchester, Essex, United Kingdom, CO45JR
    • Romford, Essex, United Kingdom, RM7 0AG
  • North Yorkshire
    • Middlesborough, North Yorkshire, United Kingdom, TS43BW
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
    • Tucson, Arizona, United States, 85724
  • California
    • Beverly Hills, California, United States, 90211-1850
    • Duarte, California, United States, 91010
    • Los Angeles, California, United States, 90073-1003
    • Stanford, California, United States, 94305-5820
  • District of Columbia
    • Washington, District of Columbia, United States, 20007-2113
  • Florida
    • Boca Raton, Florida, United States, 33486
    • Gainesville, Florida, United States, 32610-0316
    • Tampa, Florida, United States, 33612-9416
  • Georgia
    • Atlanta, Georgia, United States, 30322
  • Illinois
    • Chicago, Illinois, United States, 60611
    • Peoria, Illinois, United States, 61615-7828
  • Kentucky
    • Louisville, Kentucky, United States, 40202
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
  • Maryland
    • Baltimore, Maryland, United States, 21231
    • Towson, Maryland, United States, 21204
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
    • Boston, Massachusetts, United States, 02111
    • Boston, Massachusetts, United States, 02114-2696
  • Michigan
    • Detroit, Michigan, United States, 48202
  • Montana
    • Billings, Montana, United States, 59102
  • Nebraska
    • Omaha, Nebraska, United States, 68130-5606
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
  • New Jersey
    • Camden, New Jersey, United States, 08143
    • Englewood, New Jersey, United States, 07361
    • Hackensack, New Jersey, United States, 07601
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
  • New York
    • Bronx, New York, United States, 10467-2490
    • Buffalo, New York, United States, 14203
    • New York, New York, United States, 10032
    • Poughkeepsie, New York, United States, 12601
    • Rochester, New York, United States, 14642
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
  • Ohio
    • Cleveland, Ohio, United States, 44106
    • Columbus, Ohio, United States, 43210
    • Columbus, Ohio, United States, 43214-2416
    • Kettering, Ohio, United States, 45409-1328
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
  • Pennsylvania
    • Bala-Cynwyd, Pennsylvania, United States, 19004
    • Camp Hill, Pennsylvania, United States, 17011
    • Pittsburgh, Pennsylvania, United States, 15212
  • South Carolina
    • Charleston, South Carolina, United States, 29414
    • Charleston, South Carolina, United States, 29401-5799
    • Greenville, South Carolina, United States, 29607
    • Myrtle Beach, South Carolina, United States, 29572
    • North Charleston, South Carolina, United States, 29406
  • Texas
    • Dallas, Texas, United States, 75231
    • Temple, Texas, United States, 76508
  • Utah
    • Salt Lake City, Utah, United States, 84112
  • Virginia
    • Charlottesville, Virginia, United States, 22908
    • Fairfax, Virginia, United States, 22031
    • Richmond, Virginia, United States, 23298-5054
  • Washington
    • Everett, Washington, United States, 98201
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226

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
• Candidates for ADT and docetaxel.
• Started ADT with or without first generation anti androgen, but no longer than 12 weeks before randomization
• An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate bone marrow, liver and renal function

Exclusion Criteria:

• Prior treatment with: LHRH agonist/antagonists; second generation androgen receptor (AR) inhibitors such as enzalutamide, ARN-509, darolutamide (ODM-201), other investigational AR inhibitors; CYP17 enzyme inhibitor such as abiraterone acetate or oral ketoconazole as antineoplastic treatment for prostate cancer; chemotherapy or immunotherapy for prostate cancer prior to randomization.
• Treatment with radiotherapy/radiopharmaceuticals within 2 weeks before randomization.
• 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)
• Had a prior malignancy. Adequately treated basal cell or squamous cell carcinoma of skin or superficial bladder cancer that has not spread behind the connective tissue layer (i.e., pTis, pTa, and pT1) is allowed, as well as any other cancer for which treatment has been completed 5 years before randomization and from which the subject has been disease-free
• Gastrointestinal disorder or procedure which is expected to interfere significantly with absorption of study treatment.
• 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: BAY1841788 /darolutamide (ODM-201)+standard ADT+Docetaxel; Co-administration of BAY 1841788 / darolutamide (ODM-201), standard ADT and docetaxel	Drug: BAY1841788 / darolutamide (ODM-201); 600mg (2 tablets of 300 mg) of darolutamide (ODM-201)/placebo twice daily with food, equivalent to a total a daily dose of 1200 mg in addition to standard ADT (luteinizing hormone releasing hormone (LHRH) agonist/antagonist or orchiectomy) and 6 cycles of docetaxel; Drug: Standard ADT (androgen deprivation therapy); As prescribed by the treating physician.; Drug: Docetaxel; As prescribed by the treating physician.
Placebo Comparator: Placebo + standard ADT + Docetaxel; Co-administration of Placebo matching BAY 1841788 / darolutamide (ODM-201) tablets, standard ADT and docetaxel	Drug: Standard ADT (androgen deprivation therapy); As prescribed by the treating physician.; Drug: Docetaxel; As prescribed by the treating physician.; Drug: Placebo; Placebo matching darolutamide (ODM-201) tablets in appearance, bid orally with food, in addition to standard ADT (luteinizing hormone releasing hormone [LHRH] agonist/antagonist or orchiectomy) and 6 cycles of docetaxel.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS From Date of Randomization Until Death From Any Cause - Number of Events	Overall survival (OS) was defined as the time from the date of randomization until death from any cause. Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance. Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data. Long-term (Survival) follow-up period: After Active follow-up, patients continued to be contacted approximately every 12 weeks by phone. The end of the Survival follow-up period was defined as when the patient died, was lost to follow-up, withdrew consent, or at the end-of-study.	From randomization of the first participant until death from any cause up to 25 OCT 2021 cut-off date 533 OS events were reached (approximate 59 months)
OS From Date of Randomization Until Death From Any Cause - Month	Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance. Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data. Long-term (Survival) follow-up period: After Active follow-up, patients continued to be contacted approximately every 12 weeks by phone. The end of the Survival follow-up period was defined as when the patient died, was lost to follow-up, withdrew consent, or at the end-of-study. Median, percentile and other 95% CIs were computed using Kaplan-Meier estimates. NA = Value cannot be estimated due to censored data	From randomization of the first participant until death from any cause up to 25 OCT 2021 cut-off date 533 OS events were reached (approximate 59 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With TEAEs	TEAEs = Treatment-emergent adverse events, were defined as any event(s) arising or worsening after the first dose of darolutamide or placebo, until 30 days after the last dose of darolutamide or placebo administration.	From the first dose of darolutamide or placebo until 30 days after the last dose of darolutamide or placebo administration up to cut-off date for the final completion analysis 11 APR 2023 (approximately 77 months)
Time to Castration-Resistant Prostate Cancer (CRPC) - Number of Events	Time to castration-resistant prostate cancer was defined as the time from randomization to the first occurrence of one of the following events: PSA progression, Radiological progression by bone lesions, or Radiological progression by soft tissue and visceral lesions. Treatment period: until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance. Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.	From randomization of the first participant to the first occurrence of an CRPC event up to 25 OCT 2021 cut-off date approximately 59 months
Time to Castration-Resistant Prostate Cancer (CRPC) - Month	Time to castration-resistant prostate cancer was defined as the time from randomization to the first occurrence of one of the following events: PSA progression, Radiological progression by bone lesions, or Radiological progression by soft tissue and visceral lesions. Treatment period: until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance. Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data. NA = Value cannot be estimated due to censored data	From randomization of the first participant to the first occurrence of an CRPC event up to 25 OCT 2021 cut-off date approximately 59 months
Time to Pain Progression - Number of Events	Time to pain progression was defined as the time from randomization to the first date a patient experienced pain progression. Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance. Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.	From randomization of the first participant to the first occurrence of a pain progression event up to 25 OCT 2021 cut-off date approximately 59 months
Time to Pain Progression - Month	Time to pain progression was defined as the time from randomization to the first date a patient experienced pain progression. Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance. Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data. NA = Value cannot be estimated due to censored data	From randomization of the first participant to the first occurrence of a pain progression event up to 25 OCT 2021 cut-off date approximately 59 months
Symptomatic Skeletal Event Free Survival (SSE-FS) - Number of Events	Symptomatic skeletal event-free survival (SSE-FS) was defined as the time from randomization to the first occurrence of an SSE or death from any cause, whichever occurred first. Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance. Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.	From randomization of the first participant to the first occurrence of an SSE event or death from any cause, whichever occurred first up to 25 OCT 2021 cut-off date approximately 59 months
Symptomatic Skeletal Event Free Survival (SSE-FS) - Month	Symptomatic skeletal event-free survival (SSE-FS) was defined as the time from randomization to the first occurrence of an SSE or death from any cause, whichever occurred first. Treatment period: until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance. Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data. NA = Value cannot be estimated due to censored data	From randomization of the first participant to the first occurrence of an SSE event or death from any cause, whichever occurred first up to 25 OCT 2021 cut-off date approximately 59 months
Time to First Symptomatic Skeletal Event (SSE) - Number of Events	Time to the first SSE was defined as the time from randomization to the first occurrence of an SSE. Identical to the definition used for SSE-FS. Death was not considered as an event in this endpoint. Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance. Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.	From randomization of the first participant to the first occurrence of an SSE event up to 25 OCT 2021 cut-off date approximately 59 months
Time to First Symptomatic Skeletal Event (SSE) - Month	Time to the first SSE was defined as the time from randomization to the first occurrence of an SSE. Identical to the definition used for SSE-FS. Death was not considered as an event in this endpoint. Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance. Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data. NA = Value cannot be estimated due to censored data	From randomization of the first participant to the first occurrence of an SSE event up to 25 OCT 2021 cut-off date approximately 59 months
Time to Initiation of Subsequent Antineoplastic Therapy - Number of Events	Time to initiation of subsequent systemic antineoplastic therapy was defined as the time from randomization to the initiation of first subsequent systemic antineoplastic therapy. Treatment period: until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance. Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.	From randomization of the first participant to the initiation of first subsequent systemic antineoplastic therapy up to 25 OCT 2021 cut-off date approximately 59 months
Time to Initiation of Subsequent Antineoplastic Therapy - Month	Time to initiation of subsequent systemic antineoplastic therapy was defined as the time from randomization to the initiation of first subsequent systemic antineoplastic therapy. Treatment period: until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance. Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data. NA = Value cannot be estimated due to censored data	From randomization of the first participant to the initiation of first subsequent systemic antineoplastic therapy up to 25 OCT 2021 cut-off date approximately 59 months
Time to Worsening of Disease-Related Physical Symptoms - Number of Events	Time to worsening of disease-related physical symptoms was defined as the time from randomization to the first date a patient experienced an increase in disease-related physical symptoms based on the NCCN-FACT-FPSI-17 questionnaire. Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance. Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.	From randomization of the first participant to the first increase in disease-related physical symptoms based on the NCCN-FACT-FPSI-17 questionnaire up to 25 OCT 2021 cut-off date approximately 59 months
Time to Worsening of Disease-Related Physical Symptoms - Month	Time to worsening of disease-related physical symptoms was defined as the time from randomization to the first date a patient experienced an increase in disease-related physical symptoms based on the NCCN-FACT-FPSI-17 questionnaire. Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance. Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.	From randomization of the first participant to the first increase in disease-related physical symptoms based on the NCCN-FACT-FPSI-17 questionnaire up to 25 OCT 2021 cut-off date approximately 59 months
Time to Initiation of Opioid Use for ≥7 Consecutive Days - Number of Events	Time to the initiation of opioid use for ≥7 consecutive days was defined as the time from randomization to the date of the first opioid use for ≥7 consecutive days. Data of opioid use related to cancer pain was included in the analysis, and opioid use for non-malignant causes was excluded. Treatment period: until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance. Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.	From randomization of the first participant to the first opioid use for ≥7 consecutive days up to 25 OCT 2021 cut-off date approximately 59 months
Time to Initiation of Opioid Use for ≥7 Consecutive Days - Month	Time to the initiation of opioid use for ≥7 consecutive days was defined as the time from randomization to the date of the first opioid use for ≥7 consecutive days. Data of opioid use related to cancer pain was included in the analysis, and opioid use for non-malignant causes was excluded. Treatment period: until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance. Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data. NA = Value cannot be estimated due to censored data	From randomization of the first participant to the first opioid use for ≥7 consecutive days up to 25 OCT 2021 cut-off date approximately 59 months

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Orion Corporation, Orion Pharma
• Investigators: Study Director: Bayer Study Director, Bayer

Publications and helpful links

General Publications

• Smith MR, Hussain M, Saad F, Fizazi K, Sternberg CN, Crawford D, Manarite J, Muslin D, Farrington T, Tombal B. Darolutamide and survival in metastatic, hormone-sensitive prostate cancer: a patient and caregiver perspective and plain language summary of the ARASENS trial. Future Oncol. 2022 Jul;18(21):2585-2597. doi: 10.2217/fon-2022-0433. Epub 2022 Jun 3.
• Smith MR, Hussain M, Saad F, Fizazi K, Sternberg CN, Crawford ED, Kopyltsov E, Park CH, Alekseev B, Montesa-Pino A, Ye D, Parnis F, Cruz F, Tammela TLJ, Suzuki H, Utriainen T, Fu C, Uemura M, Mendez-Vidal MJ, Maughan BL, Joensuu H, Thiele S, Li R, Kuss I, Tombal B; ARASENS Trial Investigators. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med. 2022 Mar 24;386(12):1132-1142. doi: 10.1056/NEJMoa2119115. Epub 2022 Feb 17.

Helpful Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe
• 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): November 30, 2016
• Primary Completion (Actual): October 25, 2021
• Study Completion (Actual): April 11, 2023

Study Registration Dates

• First Submitted: June 6, 2016
• First Submitted That Met QC Criteria: June 10, 2016
• First Posted (Estimated): June 15, 2016

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: March 24, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• 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; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Docetaxel; Androgens
• Other Study ID Numbers: 17777; 2015-002590-38 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Availability of this study's data will later 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.vivli.org 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 member 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