AzTrials
AzTrials

Metastatic Castration Resistant Prostate CancerPhase 3PRESIDENCT02288247

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

A Phase 3 study testing Enzalutamide, Docetaxel and Prednisolone in people with Metastatic Castration Resistant Prostate Cancer, run by Astellas Pharma Europe Ltd. at 89 sites in 16 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Enzalutamide, Docetaxel and Prednisolone
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
688 participants
Where
89 sitesin 16 countries
Study dates
1 Dec 2014to 15 Mar 2024
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
Show all 10Show fewer
  • 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.

Who cannot join

  • 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;
Show all 13Show fewer
  • 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

Trial locations and contacts

89 sites in 16 countries.

89 sites in 16 countries

Germany10 sites

  • Site DE49008

    Aachen, 52074

  • Site DE49010

    Bergisch Gladbach, 51465

  • Site DE49001

    Hanover, 30625

  • Site DE49006

    Heidelberg, 69120

  • Site DE49003

    Mannheim, 68167

  • Site DE49002

    Münster, 48149

  • Site DE49018

    Nürtingen, Baden-Wurttemberg, 72622

  • Site DE49015

    Tübingen, 72076

  • Site DE49017

    Ulm, 89075

  • Site DE49004

    Wuppertal, 42103

Other trials in Germany

Spain10 sites

  • Site ES34005

    Lugo, 27003

  • Site ES34003

    Madrid, 28007

  • Site ES34001

    Madrid, 28040

  • Site ES34002

    Madrid, 28041

  • Site ES34010

    Madrid

  • Site ES34007

    Málaga, 29010

  • Site ES34009

    Murcia, 30008

  • Site ES34008

    Santander, 39008

  • Site ES34004

    Seville, 41013

  • Site ES34006

    Valencia, 46009

Other trials in Spain

United Kingdom10 sites

  • Site GB44010

    Aberdeen, AB25 2ZN

  • Site GB44004

    Cambridge, CB2 0QQ

  • Site GB44018

    Cardiff, CF4 7XL

  • Site GB44014

    Exeter

  • Site GB44003

    London, SE1 9RT

  • Site GB44007

    Metropolitan Borough of Wirral, CH63 4JY

  • Site GB44020

    Northwood, HA62RN

  • Site GB44015

    Norwich, NR4 7UY

  • Site GB44002

    Nottingham, NG5 1PB

  • Site GB44017

    Swansea, SA2 8QA

Other trials in United Kingdom

France9 sites

  • Site FR33012

    Albi, 81000

  • Site FR33003

    Montpellier, 34298 cedex 5

  • Site FR33002

    Nîmes, 30907 cedex 2

  • Site FR33008

    Paris, 75014

  • Site FR33014

    Paris, 75014

  • Site FR33004

    Plérin, 22190

  • Site FR33013

    Quimper, 29000

  • Site FR33011

    Reims, 51056

  • Site FR33005

    Suresnes, 92151

Other trials in France

Italy8 sites

  • Site IT39001

    Arezzo, 52100

  • Site IT39012

    Brescia, 25126

  • Site IT39003

    Milan, 20100

  • Site IT39008

    Naples, 80131

  • Site IT39010

    Pavia, 27100

  • Site IT39005

    Roma, 00128

  • Site IT39004

    Rome, 161

  • Site IT39002

    Terni, 05100

Other trials in Italy

Russia6 sites

  • Site RU70002

    Moscow, 105077

  • Site RU70001

    Moscow, 115478

  • Site RU70003

    Moscow, 125284

  • Site RU70004

    Obninsk, Kaluga Oblast, 24903

  • Site RU70005

    Saint Petersburg, 197022

  • Site RU70006

    Saint Petersburg, 197758

Other trials in Russia

Greece5 sites

  • Site GR30003

    Athens, 14564

  • Site GR30006

    Athens, 155 62

  • Site GR30001

    Heraklion, Crete, 70013

  • Site GR30004

    Heraklion, Crete, 71403

  • Site GR30005

    Thessaloniki, 54007

Other trials in Greece

Netherlands5 sites

  • Site NL31002

    Amsterdam, 1066 CX

  • Site NL31007

    Blaricum, 1261 AN

  • Site NL31004

    Hoofddorp, 2134 TM

  • Site NL31010

    Nieuwegein, 3435 CM

  • Site NL31003

    Rotterdam, 3045 PM

Other trials in Netherlands

Poland5 sites

  • Site PL48004

    Gdansk, 80-952

  • Site PL48003

    Krakow, 31-501

  • Site PL48002

    Lodz, 93-513

  • Site PL48006

    Warsaw, 02-507

  • Site PL48005

    Warsaw, 04-141

Other trials in Poland

Czechia4 sites

  • Site CZ42004

    Brno, 656 91

  • Site CZ42003

    Olomouc, 77520

  • Site CZ42002

    Plzeň -Lochotín, 30460

  • Site CZ42001

    Prague, 12808

Other trials in Czechia

Sweden4 sites

  • Site SE46002

    Gothenburg, 413 45

  • Site SE46005

    Kalmar, 39185

  • Site SE46003

    Solna, 171 76

  • Site SE46004

    Uppsala, 751 85

Other trials in Sweden

Belgium3 sites

  • Site BE32003

    Bonheiden, 2820

  • Site BE32002

    Liège, 4000

  • Site BE32004

    Ottignies, 1340

Other trials in Belgium

Norway3 sites

  • Site NO47005

    Drammen, 3004

  • Site NO47001

    Kristiansand, 4615

  • Site NO47004

    Stavanger, 4011

Other trials in Norway

Turkey (Türkiye)3 sites

  • Site TR90001

    Ankara, 06500

  • Site TR90003

    Istanbul, 34722

  • Site TR90002

    Izmir, 35340

Other trials in Turkey (Türkiye)

Austria2 sites

  • Site AT43004

    Linz, 4010

  • Site AT43001

    Vienna, 1090

Other trials in Austria

Switzerland2 sites

  • Site CH41005

    Locarno, Canton Ticino, 6600

  • Site CH41009

    Zurich, CH-8038

Other trials in Switzerland

About this study

Official title: A Randomized, Double Blind, Placebo-Controlled, Phase IIIb Study of the Efficacy and Safety of Continuing Enzalutamide in Chemotherapy Naïve Metastatic Castration Resistant Prostate Cancer Patients Treated With Docetaxel Plus Prednisolone Who Have Progressed on Enzalutamide Alone

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.

Read the 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.

Being tested
Enzalutamide, Docetaxel, Prednisolone, Placebo
Keywords
Metastatic, Castration-resistant, Docetaxel, Chemotherapy- Naïve, Enzalutamide, Prostate Cancer, Chemotherapy Naïve Metastatic Castration Resistant Prostate Cancer, Prednisolone, Xtandi, Metastatic Castration Resistant Prostate Cancer
Medical subject headings
Neoplasm Metastasis, Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02288247
Study groupRoleWhat they receive
EnzalutamideExperimentalParticipants (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.
Receives: Drug: Enzalutamide; Drug: Docetaxel; Drug: Prednisolone
PlaceboPlacebo comparatorParticipants 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.
Receives: Drug: Docetaxel; Drug: Prednisolone; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (8)

  1. Time to Prostate-specific Antigen (PSA) Progression

    Time to PSA progression, defined as the time from randomization (Period 2 Week 1) to the date of the first PSA value in Period 2 demonstrating progression (Period 2). The PSA progression date is defined as the date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir recorded in Period 2 is documented, which must be confirmed by a second consecutive value obtained at least 3 weeks later.

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

  2. Prostate-specific Antigen (PSA) Response

    PSA response, defined as a decrease in percentage change from randomization (Period 2 Week 1) of 50% or more. PSA response was derived at Week 13 and at any time after randomization in Period 2. PSA response at any time is defined as a decrease in percentage change from randomization (Period 2 Week 1) at any time after randomization of 50% or more. Percentage of participants with PSA response was reported.

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

  3. Objective Response Rate (ORR)

    ORR, defined as the best overall radiographic response after randomization (Period 2 Week 1) as per Investigator assessments of response for soft tissue disease per RECIST 1.1, in participants who had a measurable tumor. ORR was reported as the percentage of participants with complete response (CR) or partial response (PR). CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters.

    Measured: From date of randomization up to median duration of 35 weeks

  4. Time to Pain Progression

    The time to an increase of >=30% from randomization (Period 2 Week 1) in average BPI-SF item scores (items 3, 4, 5, 6) at two consecutive evaluations >=3 weeks apart without decrease in analgesic score according to the World health Organization (WHO). Only participants with an average pain intensity item score >=4 were considered. The BPI-SF was an instrument to document pain-related functional impairment and contains 7 questions which included pain intensity [(items 3, 4, 5 and 6): worst pain, least pain, average pain and current pain, with scales from 0 (no pain) to 10 (pain as bad as you can imagine)] and pain interference ](items 9A to 9G): general activity, mood, walking ability, normal work, relations with other people, sleep and enjoyment of life, with scales from 0 (does not interfere) to 10 (completely interferes)]. The BPI-SF total score for pain intensity was calculated as the mean of the 4 scores for the 4 items of pain intensity.

    Measured: From date of randomization up to median duration of 35 weeks

  5. Time to Opiate Use for Cancer-related Pain

    Time to opiate use for cancer-related pain, defined as the time from randomization (Period 2 Week 1) to initiation of chronic administration of opiate analgesia [parenteral opiate use for ≥7 days or use of WHO Analgesic Ladder Level 3 oral opiates for ≥3 weeks].

    Measured: From date of randomization up to median duration of 35 weeks

  6. Time to First Skeletal-related Event (SRE)

    Time to first SRE, defined as the time from randomization (Period 2 Week 1) to radiation therapy or surgery to bone, pathologic bone fracture, spinal cord compression, or change of antineoplastic therapy to treat bone pain.

    Measured: From date of randomization up to median duration of 35 weeks

  7. Change From Baseline in Functional Assessment of Cancer Therapy - Prostate (FACT-P)

    FACT-P quality of life questionnaire is a multi-dimensional, self-reported quality of life instrument specifically designed for use with prostate cancer participants. It consists of 27 core items which assess participant function in four domains rated on 0 to 4 Likert-type scale: physical well-being (PWB) (7 items; 0 [worst] to 4 [better], score range 0-28), social/family well-being (SWB) (7 items; 0 [worst] to 4 [better], score range 0-28), emotional well-being (EWB) (6 items; 0 [worst] to 4 [better], score range 0-24), and functional well-being (FWB) (7 items; 0 [worst] to 4 [better], score range 0-28), which is further supplemented by 12 site-specific items to assess for prostate-related symptoms (Prostate Cancer Subscale [PCS] 12 items rated on Likert-type scale 0 [worst] to 4 [better], score range 0-48). The total domain scores and PCS subscale score are then combined to a global quality of life score ranging between 0 to 156; higher scores representing better quality of life.

    Measured: Period 2: Baseline, weeks 1, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181

  8. Change From Baseline in EuroQOL 5-dimension 5-level Questionnaire [EQ-5D-5L] Visual Analog Scale (VAS)

    The EQ-5D-5L VAS records the participant's self-rated health on a vertical visual analogue scale, where the endpoints are labelled from 0 (worst health imaginable) to 100 (best health imaginable).

    Measured: Period 2: Baseline, weeks 1, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Nov 2014 (estimated)
  2. Study start1 Dec 2014
  3. Primary completion30 Apr 2020
  4. Study completion15 Mar 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
688 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02288247
Sponsor's protocol ID
9785-MA-1001
Other IDs
2013-004711-50
Acronym
PRESIDE
Status last verified
Apr 2025
First submitted
7 Nov 2014
Last updated
8 Apr 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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/.

Publications

  • 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.

    PubMed 36265504

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Enzalutamide, Docetaxel and Prednisolone in people with Metastatic Castration Resistant Prostate Cancer, run by Astellas Pharma Europe Ltd. at 89 sites in 16 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 89 sites in Germany, Spain, United Kingdom, France, Italy and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) (time frame: From date of randomization to the earliest of either documented disease progression (median duration: 35 weeks)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02288247, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in