A Study of Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC)
NCT ID: NCT02677896
Last Updated: 2025-10-24
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
1150 participants
INTERVENTIONAL
2016-03-09
2024-07-31
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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Enzalutamide + Androgen Deprivation Therapy (ADT)
Participants received 160 mg enzalutamide orally once daily during double-blind treatment period until radiographic progression was documented or until the participants started an investigational agent or new therapy for treatment of prostate cancer or until any other discontinuation criterion was met. Eligible participants who received enzalutamide during double-blind treatment period and provided informed consent to take part in open-label period continued to receive 160 mg enzalutamide orally once daily in open-label period until disease progression, unacceptable toxicity or any other discontinuation criteria were met. ADT (either bilateral orchiectomy or Luteinizing hormone-releasing hormone (LHRH) agonist/antagonist) was maintained during study treatment as per standard of care and provided by the site's pharmacy stock.
Enzalutamide
Oral
Placebo + Androgen Deprivation Therapy (ADT)
Participants received matching placebo orally once daily during double-blind treatment period until radiographic progression was documented or until the participants started an investigational agent or new therapy for treatment of prostate cancer or until any other discontinuation criterion was met. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment as per standard of care and provided by the site's pharmacy stock.
Placebo
Oral
Placebo followed by Enzalutamide
Eligible participants who received enzalutamide matching placebo during double-blind treatment period and provided informed consent to take part in open-label period switched to receive 160 mg enzalutamide orally once daily in open-label period until disease progression, unacceptable toxicity or any other discontinuation criteria were met. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment as per standard of care and provided by the site's pharmacy stock.
Enzalutamide
Oral
Interventions
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Enzalutamide
Oral
Placebo
Oral
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Subject is diagnosed with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation, signet cell or small cell histology.
* Subject has metastatic prostate cancer documented by positive bone scan (for bone disease) or metastatic lesions on computed tomography (CT) or magnetic resonance imaging (MRI) scan (for soft tissue). Subjects whose disease spread is limited to regional pelvic lymph nodes are not eligible.
* Once randomized at day 1, subject must maintain ADT with an LHRH agonist or antagonist during study treatment or have a history of bilateral orchiectomy (i.e., medical or surgical castration).
* Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Subject received randomized double-blind treatment in ARCHES
* Subject has not met any of the discontinuation criteria in the main ARCHES protocol
* Subject is willing to maintain ADT with LHRH agonist or antagonist or has had a bilateral orchiectomy.
* Subject is able to swallow enzalutamide capsules whole and to comply with study requirements throughout the study
* Subject and subject's female partner agree to follow contraception and sperm donation requirements in main protocol
Exclusion Criteria
* Up to 3 months of ADT with LHRH agonists or antagonists or orchiectomy with or without concurrent antiandrogens prior to day 1, with no radiographic evidence of disease progression or rising PSA levels prior to day 1;
* Subject may have 1 course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease if it was administered at least 4 weeks prior to day 1;
* Up to 6 cycles of docetaxel therapy with final treatment administration completed within 2 months of day 1 and no evidence of disease progression during or after the completion of docetaxel therapy;
* Up to 6 months of ADT with LHRH agonists or antagonists or orchiectomy with or without concurrent antiandrogens prior to day 1 if subject was treated with docetaxel, with no radiographic evidence of disease progression or rising PSA levels prior to day 1;
* Prior ADT given for \< 39 months in duration and \> 9 months before randomization as neoadjuvant/adjuvant therapy.
* Subject had a major surgery within 4 weeks prior to day 1.
* Subject received treatment with 5-α reductase inhibitors (finasteride, dutasteride) within 4 weeks prior to day 1.
* Subject received treatment with estrogens, cyprotoerone acetate or androgens within 4 weeks prior to day 1.
* Subject received treatment with systemic glucocorticoids greater than the equivalent of 10 mg per day of prednisone within 4 weeks prior to day 1, intended for the treatment of prostate cancer.
* Subject received treatment with herbal medications that have known hormonal antiprostate cancer activity and/or are known to decrease PSA levels within 4 weeks prior to day 1.
* Subject received prior aminoglutethimide, ketoconazole, abiraterone acetate or enzalutamide for the treatment of prostate cancer or participation in a clinical study of an investigational agent that inhibits the AR or androgen synthesis (e.g., TAK-700, ARN-509, ODM-201).
* Subject has known or suspected brain metastasis or active leptomeningeal disease.
* Subject has absolute neutrophil count \< 1500/μL, platelet count \< 100000/μL or hemoglobin \< 10 g/dL (6.2 mmol/L).
* Subject has total bilirubin (TBL) ≥ 1.5 x the upper limit of normal (ULN) (except subjects with documented Gilbert's disease), or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2.5 x the ULN .
* Subject has creatinine \> 2 mg/dL (177 μmol/L).
* Subject has albumin \< 3.0 g/dL (30 g/L).
* Subject has a history of seizure or any condition that may predispose to seizure.
* Subject has history of loss of consciousness or transient ischemic attack within 12 months prior to day 1.
* Subject has clinically significant cardiovascular disease.
* Subject received bisphosphonates or denosumab within 2 weeks prior to day 1 unless administered at stable dose or to treat diagnosed osteoporosis
* Subject has taken commercially available enzalutamide (Xtandi).
* Subject's disease has progressed radiographically during the double-blind period of the study and treatment with study drug was stopped prior to study-wide unblinding. (Note: Subjects who progressed radiographically while in the double-blind portion of the study and continued treatment per protocol are allowed to participate in the open label extension.)
* After study-wide unblinding, subject has started any new investigational agent or anti-neoplastic therapy intended to treat prostate cancer
* Subject has any clinically significant disorder or condition including excessive alcohol or drug abuse, or secondary malignancy, which may interfere with study participation
* Subject has current or previously treated brain metastasis or active leptomeningeal disease
* Subject has a history of seizure or any condition that may increase the risk of seizure
18 Years
MALE
No
Sponsors
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Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
INDUSTRY
Astellas Pharma Global Development, Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Medical Director
Role: STUDY_DIRECTOR
Astellas Pharma Global Development, Inc.
Locations
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Site US10016
Homewood, Alabama, United States
Site US10007
Anchorage, Alaska, United States
Site US10008
Tucson, Arizona, United States
Site US10034
Fountain Valley, California, United States
Site US10056
La Jolla, California, United States
Site US10026
Santa Rosa, California, United States
Site US10035
Aurora, Colorado, United States
Site US10050
Denver, Colorado, United States
Site US10048
St. Petersburg, Florida, United States
Site US10054
Thomasville, Georgia, United States
Site US10015
Chicago, Illinois, United States
Site US10043
Springfield, Illinois, United States
Site US10045
Jeffersonville, Indiana, United States
Site US10020
West Des Moines, Iowa, United States
Site US10055
Kansas City, Kansas, United States
Site US10017
Towson, Maryland, United States
Site US10036
Omaha, Nebraska, United States
Site US10018
Lawrenceville, New Jersey, United States
Site US10025
Newburgh, New York, United States
Site US10029
Syracuse, New York, United States
Site US10068
Charlotte, North Carolina, United States
Site US10009
Concord, North Carolina, United States
Site US10014
Durham, North Carolina, United States
Site US10060
Greenville, North Carolina, United States
Site US10044
Middleburg Heights, Ohio, United States
Site US10011
Lancaster, Pennsylvania, United States
Site US10012
Myrtle Beach, South Carolina, United States
Site US10059
Nashville, Tennessee, United States
Site US10046
Dallas, Texas, United States
Site US10004
Dallas, Texas, United States
Site US10040
Virginia Beach, Virginia, United States
Site US10002
Burien, Washington, United States
Site US10013
Seattle, Washington, United States
Site US10028
Wenatchee, Washington, United States
Site AR54002
Rosario, Santa Fe Province, Argentina
Site AR54007
San Miguel de Tucumán, Tucumán Province, Argentina
Site AR54010
Buenos Aires, , Argentina
Site AU61016
Camperdown, New South Wales, Australia
Site AU61007
St Leonards, New South Wales, Australia
Site AU61006
Sydney, New South Wales, Australia
Site AU61009
Tweed Heads, New South Wales, Australia
Site AU61013
Waratah, New South Wales, Australia
Site AU61001
Woodville South, South Australia, Australia
Site AU61004
Ballarat, Victoria, Australia
Site AU61015
Clayton, Victoria, Australia
Site AU61017
Parkville, Victoria, Australia
Site AU61008
St Albans, Victoria, Australia
Site BE32001
Mons, Hainaut, Belgium
Site BE32012
Ghent, Oost-Vlaanderen, Belgium
Site BE32005
Kortrijk, West-Vlaanderen, Belgium
Site BE32008
Liège, , Belgium
Site BE32007
Yvoir, , Belgium
Site CA15016
Edmonton, Alberta, Canada
Site CA15024
Abbotsford, British Columbia, Canada
Site CA15003
Kelowna, British Columbia, Canada
Site CA15022
Kelowna, British Columbia, Canada
Site CA15010
Brampton, Ontario, Canada
Site CA15021
Kingston, Ontario, Canada
Site CA15013
Oakville, Ontario, Canada
Site CA15020
Toronto, Ontario, Canada
Site CA15023
Granby, Quebec, Canada
Site CA15004
Montreal, Quebec, Canada
Site CL56002
Temuco, Región de la Araucanía, Chile
Site CL56005
Viña del Mar, Región de Valparaíso, Chile
Site CL56001
Santiago, RM, Chile
Site CL56007
Providencia, Santiago Metropolitan, Chile
Site CL56004
Reñaca, Viña Del Mar, Chile
Site CL56003
Santiago, , Chile
Site DK45005
Aarhus, Central Jutland, Denmark
Site DK45008
Holstebro, Central Jutland, Denmark
Site DK45002
Copenhagen, Hovestaden, Denmark
Site DK45004
Aalborg, North Denmark, Denmark
Site DK45003
Herlev, , Denmark
Site DK45001
Odense C, , Denmark
Site FI35802
Helsinki, Etelä-Suomen Lääni, Finland
Site FI35804
Pori, Länsi-Suomen Lääni, Finland
Site FI35803
Seinäjoki, Länsi-Suomen Lääni, Finland
Site FI35801
Tampere, Oulun Laani, Finland
Site FI35806
Jakobstad, , Finland
Site FI35805
Oulu, , Finland
Site FI35807
Turku, , Finland
Site FR33010
Angers, Maine-et-Loire, France
Site FR33003
Créteil, Val-de-Marne, France
Site FR33006
Bordeaux, , France
Site FR33014
Caen, , France
Site FR33005
La Roche-sur-Yon, , France
Site FR33015
Le Mans, , France
Site FR33012
Lille, , France
Site FR33007
Lyon, , France
Site FR33011
Nîmes, , France
Site FR33001
Pierre-Bénite, , France
Site FR33009
Quimper, , France
Site FR33013
Saint-Mandé, , France
Site DE49002
Freiburg im Breisgau, Baden-Wurttemberg, Germany
Site DE49004
Nürtingen, Baden-Wurttemberg, Germany
Site DE49005
Bonn, , Germany
Site DE49014
Hamburg, , Germany
Site DE49013
Heidelberg, , Germany
Site IL97201
Kfar Saba, Central District, Israel
Site IL97211
Ẕerifin, Central District, Israel
Site IL97210
Beersheba, , Israel
Site IL97202
Haifa, , Israel
Site IL97205
Haifa, , Israel
Site IL97206
Jerusalem, , Israel
Site IT39005
Meldola, Emilia-Romagna, Italy
Site IT39004
Cremona, Lombardy, Italy
Site IT39003
Milan, Lombardy, Italy
Site IT39012
Milan, Lombardy, Italy
Site IT39007
Novara, Piedmont, Italy
Site IT39011
Trento, Trentino-Alto Adige, Italy
Site IT39008
Pisa, Tuscany, Italy
Site IT39006
Padua, Veneto, Italy
Site IT39009
Candiolo, , Italy
Site JP81003
Sakura, Chiba, Japan
Site JP81001
Maebashi, Gunma, Japan
Site JP81013
Kita-gun, Kagawa-ken, Japan
Site JP81007
Yokohama, Kanagawa, Japan
Site JP81016
Sendai, Miyagi, Japan
Site JP81010
Abeno-ku, Osaka, Japan
Site JP81011
Chuo-ku, Osaka, Japan
Site JP81012
Sayama, Osaka, Japan
Site JP81006
Bunkyo-ku, Tokyo, Japan
Site JP81004
Koto-ku, Tokyo, Japan
Site JP81005
Shinjuku-ku, Tokyo, Japan
Site JP81017
Ube, Yamaguchi, Japan
Site JP81002
Chiba, , Japan
Site JP81014
Fukuoka, , Japan
Site JP81015
Fukuoka, , Japan
Site JP81008
Kyoto, , Japan
Site JP81018
Nagasaki, , Japan
Site JP81020
Niigata, , Japan
Site JP81019
Yamagata, , Japan
Site NL31003
Nijmegen, Gelderland, Netherlands
Site NL31007
Nijmegen, Gelderland, Netherlands
Site NL31005
Eindhoven, North Brabant, Netherlands
Site NL31010
Alkmaar, North Holland, Netherlands
Site NL31008
Amsterdam, North Holland, Netherlands
Site NL31009
Zwolle, Overijssel, Netherlands
Site NL31002
Sneek, Provincie Friesland, Netherlands
Site NL31006
Rotterdam, South Holland, Netherlands
Site NZ64003
Tauranga, Bay of Plenty, New Zealand
Site NZ64008
Kensington, Northland, New Zealand
Site NZ64002
Dunedin, South Island, New Zealand
Site NZ64005
Nelson, Tasman District, New Zealand
Site NZ64004
Hamilton, , New Zealand
Site PL48007
Krakow, Lesser Poland Voivodeship, Poland
Site PL48003
Wroclaw, Lower Silesian Voivodeship, Poland
Site PL48011
Warsaw, Masovian Voivodeship, Poland
Site PL48005
Gdansk, Pomeranian Voivodeship, Poland
Site PL48010
Słupsk, Pomeranian Voivodeship, Poland
Site PL48001
Mysłowice, , Poland
Site RO40008
Cluj-Napoca, Cluj, Romania
Site RO40009
Cluj-Napoca, Cluj, Romania
Site RO40002
Floreşti, Cluj, Romania
Site RO40011
Timișoara, Timiș County, Romania
Site RO40007
Brasov, , Romania
Site RO40003
Bucharest, , Romania
Site RO40006
Bucharest, , Romania
Site RU70013
Ivanovo, , Russia
Site RU70001
Moscow, , Russia
Site RU70003
Moscow, , Russia
Site RU70014
Moscow, , Russia
Site RU70006
Omsk, , Russia
Site RU70005
Penza, , Russia
Site RU70007
Saint Petersburg, , Russia
Site RU70008
Saint Petersburg, , Russia
Site RU70009
Saint Petersburg, , Russia
Site RU70012
Saint Petersburg, , Russia
Site RU70016
Saint Petersburg, , Russia
Site SK42110
Bratislava, , Slovakia
Site SK42109
Košice, , Slovakia
Site SK42102
Michalovce, , Slovakia
Site SK42103
Nitra, , Slovakia
Site SK42101
Poprad, , Slovakia
Site SK42107
Trenčín, , Slovakia
Site SK42106
Žilina, , Slovakia
Site KR82008
Seongnam-si, Gyeonggi-do, South Korea
Site KR82007
Busan, , South Korea
Site KR82004
Incheon, , South Korea
Site KR82001
Seoul, , South Korea
Site KR82002
Seoul, , South Korea
Site KR82003
Seoul, , South Korea
Site ES34011
Salamanca, A Coruña, Spain
Site ES34010
Sabadell, Barcelona, Spain
Site ES34012
Barcelona, Catalonia, Spain
Site ES34014
Barcelona, Catalonia, Spain
Site ES34006
Pamplona, Navarre, Spain
Site ES34020
Oviedo, Principality of Asturias, Spain
Site ES34013
Valencia, Valencia, Spain
Site ES34001
Ávila, , Spain
Site ES34007
Barcelona, , Spain
Site ES34004
Madrid, , Spain
Site ES34019
Madrid, , Spain
Site SE46002
Örebro, Orebro Län, Sweden
Site SE46001
Malmo, Skåne County, Sweden
Site SE46006
Stockholm, Södermanland County, Sweden
Site SE46004
Sundsvall, Västernorrland County, Sweden
Site SE46007
Gothenburg, Västra Götaland County, Sweden
Site TW88601
Kaohsiung City, , Taiwan
Site TW88606
Taichung, , Taiwan
Site TW88605
Taipei, , Taiwan
Site TW88607
Taoyuan District, , Taiwan
Site GB44002
Withington, Manchester, United Kingdom
Countries
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References
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Armstrong AJ, Szmulewitz RZ, Petrylak DP, Holzbeierlein J, Villers A, Azad A, Alcaraz A, Alekseev B, Iguchi T, Shore ND, Rosbrook B, Sugg J, Baron B, Chen L, Stenzl A. ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy With Enzalutamide or Placebo in Men With Metastatic Hormone-Sensitive Prostate Cancer. J Clin Oncol. 2019 Nov 10;37(32):2974-2986. doi: 10.1200/JCO.19.00799. Epub 2019 Jul 22.
Azad AA, Petrylak DP, Iguchi T, Shore ND, Villers A, Gomez-Veiga F, Alcaraz A, Alekseev B, Szmulewitz RZ, Holzbeierlein J, Rosbrook B, Ma J, Zohren F, El-Chaar NN, Haas GP, Stenzl A, Armstrong AJ. Enzalutamide and Prostate-Specific Antigen Levels in Metastatic Prostate Cancer: A Secondary Analysis of the ARCHES Randomized Clinical Trial. JAMA Netw Open. 2025 May 1;8(5):e258751. doi: 10.1001/jamanetworkopen.2025.8751.
Armstrong AJ, Azad AA, Conduit C, Haas GP, Bland C, Davis ID. Enzalutamide in metastatic hormone-sensitive prostate cancer: A plain language summary of the ARCHES and ENZAMET follow-up studies. Future Oncol. 2025 Jan;21(1):15-24. doi: 10.1080/14796694.2024.2408101. Epub 2024 Oct 15.
Armstrong AJ, Iguchi T, Azad AA, Villers A, Alekseev B, Petrylak DP, Szmulewitz RZ, Alcaraz A, Shore ND, Holzbeierlein J, Gomez-Veiga F, Rosbrook B, Zohren F, Haas GP, Gourgiotti G, El-Chaar N, Stenzl A. The Efficacy of Enzalutamide plus Androgen Deprivation Therapy in Oligometastatic Hormone-sensitive Prostate Cancer: A Post Hoc Analysis of ARCHES. Eur Urol. 2023 Aug;84(2):229-241. doi: 10.1016/j.eururo.2023.04.002. Epub 2023 May 12.
Cella D, Ganguli A, Turnbull J, Rohay J, Morlock R. US Population Reference Values for Health-Related Quality of Life Questionnaires Based on Demographics of Patients with Prostate Cancer. Adv Ther. 2022 Aug;39(8):3696-3710. doi: 10.1007/s12325-022-02204-3. Epub 2022 Jun 22.
Armstrong AJ, Azad AA, Iguchi T, Szmulewitz RZ, Petrylak DP, Holzbeierlein J, Villers A, Alcaraz A, Alekseev B, Shore ND, Gomez-Veiga F, Rosbrook B, Zohren F, Yamada S, Haas GP, Stenzl A. Improved Survival With Enzalutamide in Patients With Metastatic Hormone-Sensitive Prostate Cancer. J Clin Oncol. 2022 May 20;40(15):1616-1622. doi: 10.1200/JCO.22.00193. Epub 2022 Apr 14.
Stenzl A, Dunshee C, De Giorgi U, Alekseev B, Iguchi T, Szmulewitz RZ, Flaig TW, Tombal B, Morlock R, Ivanescu C, Ramaswamy K, Saad F, Armstrong AJ. Effect of Enzalutamide plus Androgen Deprivation Therapy on Health-related Quality of Life in Patients with Metastatic Hormone-sensitive Prostate Cancer: An Analysis of the ARCHES Randomised, Placebo-controlled, Phase 3 Study. Eur Urol. 2020 Oct;78(4):603-614. doi: 10.1016/j.eururo.2020.03.019. Epub 2020 Apr 23.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
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Link to results and other applicable study documents on the Astellas Clinical Trials website.
Link to plain language summary of the study on the Trial Results Summaries website.
Other Identifiers
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2015-003869-28
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
9785-CL-0335
Identifier Type: -
Identifier Source: org_study_id
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