NCT02288247

Brief Summary

The purpose of the study was to understand if there was benefit in continued treatment with a medicine called enzalutamide, when starting treatment with docetaxel and prednisolone (a standard chemotherapy for prostate cancer), after the prostate cancer had gotten worse when treated with enzalutamide alone.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
688

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Dec 2014

Longer than P75 for phase_3

Geographic Reach
16 countries

89 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 7, 2014

Completed
4 days until next milestone

First Posted

Study publicly available on registry

November 11, 2014

Completed
20 days until next milestone

Study Start

First participant enrolled

December 1, 2014

Completed
5.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 30, 2020

Completed
1.6 years until next milestone

Results Posted

Study results publicly available

December 15, 2021

Completed
2.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 15, 2024

Completed
Last Updated

April 8, 2025

Status Verified

April 1, 2025

Enrollment Period

5.4 years

First QC Date

November 7, 2014

Results QC Date

September 29, 2021

Last Update Submit

April 4, 2025

Conditions

Keywords

MetastaticCastration-resistantDocetaxelChemotherapy- NaïveEnzalutamideProstate CancerChemotherapy Naïve Metastatic Castration Resistant Prostate CancerPrednisoloneXtandiMetastatic Castration Resistant Prostate Cancer

Outcome Measures

Primary Outcomes (1)

  • Progression Free Survival (PFS)

    PFS: time from randomization (Period 2 Week 1) to earliest progression event. Progression is defined as radiographic progression, unequivocal clinical progression, or death on study. Radiographic progression is defined for bone disease by appearance of ≥ 2 new lesions on whole-body radionuclide bone scan per Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria (i.e., unconfirmed progressive disease) that needs to be confirmed in the next assessment (i.e., progressive disease in the next assessment) or for soft tissue disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Unequivocal clinical progression is defined as new onset cancer pain requiring chronic administration of opiate analgesia or deterioration from prostate cancer of Eastern Cooperative Oncology Group (ECOG) performance status score to ≥ 3, or initiation of subsequent lines of cytotoxic chemotherapy or radiation therapy or surgical intervention due to complications of tumor progression.

    From date of randomization to the earliest of either documented disease progression (median duration: 35 weeks)

Secondary Outcomes (8)

  • Time to Prostate-specific Antigen (PSA) Progression

    From date of randomization to the first PSA value (median duration: 35 weeks)

  • Prostate-specific Antigen (PSA) Response

    Randomization, Week 13, any time after randomization in Period 2 (median of 35 weeks)

  • Objective Response Rate (ORR)

    From date of randomization up to median duration of 35 weeks

  • Time to Pain Progression

    From date of randomization up to median duration of 35 weeks

  • Time to Opiate Use for Cancer-related Pain

    From date of randomization up to median duration of 35 weeks

  • +3 more secondary outcomes

Study Arms (2)

Enzalutamide

EXPERIMENTAL

Participants (Pts) received OL enzalutamide 160 mg QD from Day 1 in Period 1 (P1) until they were either randomized to Period 2 (P2), were ineligible, experienced intolerable toxicity, withdrew, or died. Pts with confirmed disease progression in P1, meeting eligibility, were randomized to receive placebo/enzalutamide 160 mg QD with docetaxel 75 mg/m\^2 in 1hour infusion every 3 weeks \& prednisolone 5mg twice daily in P2. Docetaxel \& prednisolone were administered for upto 10 cycles (1 cycle=3 weeks) or more per investigator discretion, while placebo/enzalutamide continued until progression, toxicity, withdrawal, or death. Extension(EXT) phase was available for Pts in P1\& P2 who were not meeting primary endpoint. Enzalutamide continued until disease progression, intolerable toxicity, withdrawal, or death. Pts not entering EXT discontinued and received local care. Those benefiting from enzalutamide in EXT at study closure continued in study 9785-CL-0123 or via commercial enzalutamide.

Drug: EnzalutamideDrug: DocetaxelDrug: Prednisolone

Placebo

PLACEBO COMPARATOR

Participants received an OL treatment with enzalutamide 160 mg capsules, orally once daily from day 1 in period 1 until randomization to period 2 treatment, confirmation of ineligibility for period 2 treatment, intolerable toxicity, withdrawal, or death, whichever occurred first. Participants with confirmed disease progression on enzalutamide in period 1 and who continued to meet all eligibility criteria received placebo matched to enzalutamide, orally once daily in combination with docetaxel 75 mg/m\^2 in a one-hour infusion every 3 weeks and prednisolone 5 mg orally twice daily, DB in period 2. Docetaxel and prednisolone were administered up to 10 cycles (1 cycle = 3 weeks) or additional cycles as assessed by the investigator and enzalutamide was administered until disease progression, intolerable toxicity, withdrawal or death, whichever occurred first. Participants discontinued the study and received local standard of care.

Drug: DocetaxelDrug: PrednisoloneDrug: Placebo

Interventions

Oral

Also known as: Xtandi, ASP9785
Enzalutamide

intravenous infusion

EnzalutamidePlacebo

Oral

EnzalutamidePlacebo

Oral

Placebo

Eligibility Criteria

Age18 Years+
Sexmale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features;
  • Ongoing androgen deprivation therapy (ADT) with a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist at a stable dose and schedule within 4 weeks of initiation of investigational medicinal product (IMP), or bilateral orchiectomy (i.e., surgical or medical castration);
  • Metastatic disease documented by at least 2 bone lesions on bone scan, or soft tissue disease documented by computed tomography (CT)/magnetic resonance imaging (MRI);
  • Progressive disease at study entry defined as the following occurring in the setting of castrate levels of testosterone: Prostate specific antigen (PSA) progression defined by a minimum of three rising PSA levels with an interval of ≥ 1 week between each determination.
  • Asymptomatic or minimally symptomatic prostate cancer (Brief Pain Inventory - Short Form (BPI-SF) question 3 score of \< 4);
  • Eastern Cooperative Oncology Group (ECOG) performance score of 0-1;
  • Estimated life expectancy of ≥ 12 months;
  • Be suitable and willing to receive chemotherapy as part of the trial;
  • Able to swallow the IMP and comply with study requirements;
  • Subject agreed not to participate in another interventional study while on treatment.

You may not qualify if:

  • Prior treatment with the following agents for the treatment of prostate cancer: Aminoglutethimide; Ketoconazole; Abiraterone; Enzalutamide or participation in a clinical trial of enzalutamide; 223Ra, 89Sr, 153Sm, 186Re/188Re; Immunomodulatory therapies; Cytotoxic chemotherapy; Participation in a clinical trial of an investigational agent that inhibits the AR or androgen synthesis unless the treatment was placebo;
  • Current or prior treatment within 4 weeks prior to initiation of investigational medicinal product (IMP) with the following agents for the treatment of prostate cancer: Antiandrogens; 5-α reductase inhibitors; Estrogens; Anabolic steroids; Drugs with antiandrogenic properties; Progestational agents;
  • Subject had received investigational therapy within 28 days or 5 half-lives whichever was longer, prior to initiation of IMP;
  • Use of opiate analgesia for pain from prostate cancer within 4 weeks prior to initiation of IMP;
  • Radiation therapy to bone lesions or prostatic bed within 4 weeks prior to initiation of IMP;
  • Major surgery within 4 weeks prior to initiation of IMP;
  • History of seizure or any condition that may predispose to seizures at any time in the past. History of loss of consciousness or transient ischemic attack within 12 months prior to Screening;
  • Known or suspected brain metastasis or active leptomeningeal disease;
  • History of another malignancy within the previous 5 years other than non-melanoma skin cancer;
  • Clinically significant cardiovascular disease;
  • Gastrointestinal disorders affecting absorption;
  • Medical contraindications to the use of prednisolone or docetaxel;
  • Allergies to any of the active ingredients or excipients in the study drugs

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (89)

Site AT43004

Linz, 4010, Austria

Location

Site AT43001

Vienna, 1090, Austria

Location

Site BE32003

Bonheiden, 2820, Belgium

Location

Site BE32002

Liège, 4000, Belgium

Location

Site BE32004

Ottignies, 1340, Belgium

Location

Site CZ42004

Brno, 656 91, Czechia

Location

Site CZ42003

Olomouc, 77520, Czechia

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Site CZ42002

Plzeň -Lochotín, 30460, Czechia

Location

Site CZ42001

Prague, 12808, Czechia

Location

Site FR33012

Albi, 81000, France

Location

Site FR33003

Montpellier, 34298 cedex 5, France

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Site FR33002

Nîmes, 30907 cedex 2, France

Location

Site FR33008

Paris, 75014, France

Location

Site FR33014

Paris, 75014, France

Location

Site FR33004

Plérin, 22190, France

Location

Site FR33013

Quimper, 29000, France

Location

Site FR33011

Reims, 51056, France

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Site FR33005

Suresnes, 92151, France

Location

Site DE49018

Nürtingen, Baden-Wurttemberg, 72622, Germany

Location

Site DE49008

Aachen, 52074, Germany

Location

Site DE49010

Bergisch Gladbach, 51465, Germany

Location

Site DE49001

Hanover, 30625, Germany

Location

Site DE49006

Heidelberg, 69120, Germany

Location

Site DE49003

Mannheim, 68167, Germany

Location

Site DE49002

Münster, 48149, Germany

Location

Site DE49015

Tübingen, 72076, Germany

Location

Site DE49017

Ulm, 89075, Germany

Location

Site DE49004

Wuppertal, 42103, Germany

Location

Site GR30001

Heraklion, Crete, 70013, Greece

Location

Site GR30004

Heraklion, Crete, 71403, Greece

Location

Site GR30003

Athens, 14564, Greece

Location

Site GR30006

Athens, 155 62, Greece

Location

Site GR30005

Thessaloniki, 54007, Greece

Location

Site IT39001

Arezzo, 52100, Italy

Location

Site IT39012

Brescia, 25126, Italy

Location

Site IT39003

Milan, 20100, Italy

Location

Site IT39008

Naples, 80131, Italy

Location

Site IT39010

Pavia, 27100, Italy

Location

Site IT39005

Roma, 00128, Italy

Location

Site IT39004

Rome, 161, Italy

Location

Site IT39002

Terni, 05100, Italy

Location

Site NL31002

Amsterdam, 1066 CX, Netherlands

Location

Site NL31007

Blaricum, 1261 AN, Netherlands

Location

Site NL31004

Hoofddorp, 2134 TM, Netherlands

Location

Site NL31010

Nieuwegein, 3435 CM, Netherlands

Location

Site NL31003

Rotterdam, 3045 PM, Netherlands

Location

Site NO47005

Drammen, 3004, Norway

Location

Site NO47001

Kristiansand, 4615, Norway

Location

Site NO47004

Stavanger, 4011, Norway

Location

Site PL48004

Gdansk, 80-952, Poland

Location

Site PL48003

Krakow, 31-501, Poland

Location

Site PL48002

Lodz, 93-513, Poland

Location

Site PL48006

Warsaw, 02-507, Poland

Location

Site PL48005

Warsaw, 04-141, Poland

Location

Site RU70004

Obninsk, Kaluga Oblast, 24903, Russia

Location

Site RU70002

Moscow, 105077, Russia

Location

Site RU70001

Moscow, 115478, Russia

Location

Site RU70003

Moscow, 125284, Russia

Location

Site RU70005

Saint Petersburg, 197022, Russia

Location

Site RU70006

Saint Petersburg, 197758, Russia

Location

Site ES34005

Lugo, 27003, Spain

Location

Site ES34003

Madrid, 28007, Spain

Location

Site ES34001

Madrid, 28040, Spain

Location

Site ES34002

Madrid, 28041, Spain

Location

Site ES34010

Madrid, Spain

Location

Site ES34007

Málaga, 29010, Spain

Location

Site ES34009

Murcia, 30008, Spain

Location

Site ES34008

Santander, 39008, Spain

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Site ES34004

Seville, 41013, Spain

Location

Site ES34006

Valencia, 46009, Spain

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Site SE46002

Gothenburg, 413 45, Sweden

Location

Site SE46005

Kalmar, 39185, Sweden

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Site SE46003

Solna, 171 76, Sweden

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Site SE46004

Uppsala, 751 85, Sweden

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Site CH41005

Locarno, Canton Ticino, 6600, Switzerland

Location

Site CH41009

Zurich, CH-8038, Switzerland

Location

Site TR90001

Ankara, 06500, Turkey (Türkiye)

Location

Site TR90003

Istanbul, 34722, Turkey (Türkiye)

Location

Site TR90002

Izmir, 35340, Turkey (Türkiye)

Location

Site GB44010

Aberdeen, AB25 2ZN, United Kingdom

Location

Site GB44004

Cambridge, CB2 0QQ, United Kingdom

Location

Site GB44018

Cardiff, CF4 7XL, United Kingdom

Location

Site GB44014

Exeter, United Kingdom

Location

Site GB44003

London, SE1 9RT, United Kingdom

Location

Site GB44007

Metropolitan Borough of Wirral, CH63 4JY, United Kingdom

Location

Site GB44020

Northwood, HA62RN, United Kingdom

Location

Site GB44015

Norwich, NR4 7UY, United Kingdom

Location

Site GB44002

Nottingham, NG5 1PB, United Kingdom

Location

Site GB44017

Swansea, SA2 8QA, United Kingdom

Location

Related Publications (1)

  • Merseburger AS, Attard G, Astrom L, Matveev VB, Bracarda S, Esen A, Feyerabend S, Senkus E, Lopez-Brea Piqueras M, Boysen G, Gourgioti G, Martins K, Chowdhury S. Continuous enzalutamide after progression of metastatic castration-resistant prostate cancer treated with docetaxel (PRESIDE): an international, randomised, phase 3b study. Lancet Oncol. 2022 Nov;23(11):1398-1408. doi: 10.1016/S1470-2045(22)00560-5. Epub 2022 Oct 18.

Related Links

MeSH Terms

Conditions

Neoplasm MetastasisProstatic Neoplasms

Interventions

enzalutamideDocetaxelPrednisolone

Condition Hierarchy (Ancestors)

Neoplastic ProcessesNeoplasmsPathologic ProcessesPathological Conditions, Signs and SymptomsGenital Neoplasms, MaleUrogenital NeoplasmsNeoplasms by SiteGenital Diseases, MaleGenital DiseasesUrogenital DiseasesProstatic DiseasesMale Urogenital Diseases

Intervention Hierarchy (Ancestors)

TaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenesPregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic Compounds

Results Point of Contact

Title
Clinical Trial Disclosure
Organization
Astellas Pharma Europe Ltd. (APEL)

Study Officials

  • Medical Director

    Astellas Pharma Europe Ltd.

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 7, 2014

First Posted

November 11, 2014

Study Start

December 1, 2014

Primary Completion

April 30, 2020

Study Completion

March 15, 2024

Last Updated

April 8, 2025

Results First Posted

December 15, 2021

Record last verified: 2025-04

Data Sharing

IPD Sharing
Will share

Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

Shared Documents
STUDY PROTOCOL, SAP, CSR
Time Frame
Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
Access Criteria
Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
More information

Locations