A Study to Assess the Benefit of Treatment Beyond Progression With Enzalutamide in Men Who Are Starting Treatment With Docetaxel After Worsening of Their Prostate Cancer When Taking Enzalutamide Alone

NCT ID: NCT02288247

Last Updated: 2025-04-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 688 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-01
• Study Completion Date: 2024-03-15

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.

Detailed Description

The study was conducted in consecutive periods of open label treatment with enzalutamide followed by randomized double-blind treatment with continued enzalutamide or placebo, in combination with docetaxel and prednisolone.

Open Label (Period 1)

Participants received open label treatment (OL) with enzalutamide. At week 13, all participants were assessed by prostate-specific antigen (PSA) and imaging. Participants with no confirmed PSA response or evidence of radiographic progression were ineligible for participation in Period 2 and typically had safety follow up; however, Period 1 treatment continued for some participants as long as the investigator considered it to be of clinical benefit (stopping on initiation of any new antineoplastic therapy). Participants with confirmed PSA response continued Period 1 until disease progression.

Enrollment to Period 2 ceased after approximately 274 participants had been enrolled or 182 primary endpoint events had been reached, whichever occurred first. Participants who were not randomized into period 2 at this time continued to receive open label treatment in an extension period.

Randomization (Double Blind [DB]) (Period 2)

Participants with confirmed disease progression on enzalutamide alone who continued to meet all eligibility criteria proceeded to randomization. Treatment allocation was in a 1:1 ratio, stratified by disease progression in Period 1 to the following treatments:

• Enzalutamide with docetaxel and prednisolone
• Placebo with docetaxel and prednisolone

Any ongoing participants in Period 2 at the point of unblinding in the enzalutamide+docetaxel arm that were still receiving and benefitting from enzalutamide treatment, had the option to continue treatment via an extension period.

Conditions

Metastatic Castration Resistant Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Enzalutamide

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.

Group Type: EXPERIMENTAL

Enzalutamide

Intervention Type: DRUG

Oral

Docetaxel

Intervention Type: DRUG

intravenous infusion

Prednisolone

Intervention Type: DRUG

Oral

Placebo

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.

Group Type: PLACEBO_COMPARATOR

Docetaxel

Intervention Type: DRUG

intravenous infusion

Prednisolone

Intervention Type: DRUG

Oral

Placebo

Intervention Type: DRUG

Oral

Interventions

Enzalutamide

Oral

Intervention Type: DRUG

Docetaxel

intravenous infusion

Intervention Type: DRUG

Prednisolone

Oral

Intervention Type: DRUG

Placebo

Oral

Intervention Type: DRUG

Other Intervention Names

Xtandi; ASP9785

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Medivation LLC, a wholly owned subsidiary of Pfizer Inc.

INDUSTRY

Sponsor Role: collaborator

Astellas Pharma Europe Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Astellas Pharma Europe Ltd.

Locations

Site AT43004

Linz, , Austria

Site AT43001

Vienna, , Austria

Site BE32003

Bonheiden, , Belgium

Site BE32002

Liège, , Belgium

Site BE32004

Ottignies, , Belgium

Site CZ42004

Brno, , Czechia

Site CZ42003

Olomouc, , Czechia

Site CZ42002

Plzeň -Lochotín, , Czechia

Site CZ42001

Prague, , Czechia

Site FR33012

Albi, , France

Site FR33003

Montpellier, , France

Site FR33002

Nîmes, , France

Site FR33008

Paris, , France

Site FR33014

Paris, , France

Site FR33004

Plérin, , France

Site FR33013

Quimper, , France

Site FR33011

Reims, , France

Site FR33005

Suresnes, , France

Site DE49018

Nürtingen, Baden-Wurttemberg, Germany

Site DE49008

Aachen, , Germany

Site DE49010

Bergisch Gladbach, , Germany

Site DE49001

Hanover, , Germany

Site DE49006

Heidelberg, , Germany

Site DE49003

Mannheim, , Germany

Site DE49002

Münster, , Germany

Site DE49015

Tübingen, , Germany

Site DE49017

Ulm, , Germany

Site DE49004

Wuppertal, , Germany

Site GR30001

Heraklion, Crete, Greece

Site GR30004

Heraklion, Crete, Greece

Site GR30003

Athens, , Greece

Site GR30006

Athens, , Greece

Site GR30005

Thessaloniki, , Greece

Site IT39001

Arezzo, , Italy

Site IT39012

Brescia, , Italy

Site IT39003

Milan, , Italy

Site IT39008

Naples, , Italy

Site IT39010

Pavia, , Italy

Site IT39005

Roma, , Italy

Site IT39004

Rome, , Italy

Site IT39002

Terni, , Italy

Site NL31002

Amsterdam, , Netherlands

Site NL31007

Blaricum, , Netherlands

Site NL31004

Hoofddorp, , Netherlands

Site NL31010

Nieuwegein, , Netherlands

Site NL31003

Rotterdam, , Netherlands

Site NO47005

Drammen, , Norway

Site NO47001

Kristiansand, , Norway

Site NO47004

Stavanger, , Norway

Site PL48004

Gdansk, , Poland

Site PL48003

Krakow, , Poland

Site PL48002

Lodz, , Poland

Site PL48006

Warsaw, , Poland

Site PL48005

Warsaw, , Poland

Site RU70004

Obninsk, Kaluga Oblast, Russia

Site RU70002

Moscow, , Russia

Site RU70001

Moscow, , Russia

Site RU70003

Moscow, , Russia

Site RU70005

Saint Petersburg, , Russia

Site RU70006

Saint Petersburg, , Russia

Site ES34005

Lugo, , Spain

Site ES34003

Madrid, , Spain

Site ES34001

Madrid, , Spain

Site ES34002

Madrid, , Spain

Site ES34010

Madrid, , Spain

Site ES34007

Málaga, , Spain

Site ES34009

Murcia, , Spain

Site ES34008

Santander, , Spain

Site ES34004

Seville, , Spain

Site ES34006

Valencia, , Spain

Site SE46002

Gothenburg, , Sweden

Site SE46005

Kalmar, , Sweden

Site SE46003

Solna, , Sweden

Site SE46004

Uppsala, , Sweden

Site CH41005

Locarno, Canton Ticino, Switzerland

Site CH41009

Zurich, , Switzerland

Site TR90001

Ankara, , Turkey (Türkiye)

Site TR90003

Istanbul, , Turkey (Türkiye)

Site TR90002

Izmir, , Turkey (Türkiye)

Site GB44010

Aberdeen, , United Kingdom

Site GB44004

Cambridge, , United Kingdom

Site GB44018

Cardiff, , United Kingdom

Site GB44014

Exeter, , United Kingdom

Site GB44003

London, , United Kingdom

Site GB44007

Metropolitan Borough of Wirral, , United Kingdom

Site GB44020

Northwood, , United Kingdom

Site GB44015

Norwich, , United Kingdom

Site GB44002

Nottingham, , United Kingdom

Site GB44017

Swansea, , United Kingdom

Countries

Austria; Belgium; Czechia; France; Germany; Greece; Italy; Netherlands; Norway; Poland; Russia; Spain; Sweden; Switzerland; Turkey (Türkiye); United Kingdom

References

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.

Reference Type: DERIVED

PMID: 36265504 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.trialsummaries.com/Study/StudyDetails?id=14680&tenant=MT_AST_9011

Link to plain language summary of the study on the Trial Results Summaries website

Other Identifiers

2013-004711-50

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

9785-MA-1001

Identifier Type: -

Identifier Source: org_study_id