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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02319837




Registration number
NCT02319837
Ethics application status
Date submitted
14/12/2014
Date registered
18/12/2014
Date last updated
28/04/2020

Titles & IDs
Public title
Safety and Efficacy Study of Enzalutamide Plus Leuprolide in Patients With Nonmetastatic Prostate Cancer (EMBARK)
Scientific title
A PHASE 3, RANDOMIZED, EFFICACY AND SAFETY STUDY OF ENZALUTAMIDE PLUS LEUPROLIDE, ENZALUTAMIDE MONOTHERAPY, AND PLACEBO PLUS LEUPROLIDE IN MEN WITH HIGH-RISK NONMETASTATIC PROSTATE CANCER PROGRESSING AFTER DEFINITIVE THERAPY
Secondary ID [1] 0 0
C3431004
Secondary ID [2] 0 0
MDV3100-13
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hormone Sensitive Prostate Cancer 0 0
Prostate Cancer 0 0
Cancer of the Prostate 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Enzalutamide
Treatment: Drugs - Placebo
Treatment: Drugs - Leuprolide

Experimental: Enzalutamide plus leuprolide - Enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily in combination with leuprolide administered as as a single intramuscular or subcutaneous injection once every 12 weeks

Experimental: Enzalutamide monotherapy - Enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily

Active Comparator: Placebo plus leuprolide - Enzalutamide placebo (placebo) capsules (identical in appearance to enzalutamide) administered as 4 capsules by mouth once daily in combination with leuprolide administered as a single intramuscular or subcutaneous injection once every 12 weeks


Treatment: Drugs: Enzalutamide


Treatment: Drugs: Placebo
Sugar pill to mimic enzalutamide

Treatment: Drugs: Leuprolide


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Metastasis-free survival (MFS) - Compared between enzalutamide plus leuprolide and placebo plus leuprolide.
Timepoint [1] 0 0
Up to approximatey 67 months
Secondary outcome [1] 0 0
Overall survival
Timepoint [1] 0 0
Up to approximately 96 months
Secondary outcome [2] 0 0
Time to castration resistance
Timepoint [2] 0 0
Up to approximately 67 months
Secondary outcome [3] 0 0
Composite of safety - Safety will be evaluated by the incidence of serious adverse events, incidence and severity of adverse events, incidence of permanent treatment discontinuation due to adverse events, and incidence of new clinically significant changes in clinical laboratory values and vital signs.
Timepoint [3] 0 0
Up to approximately 67 months
Secondary outcome [4] 0 0
Metastasis-free survival (MFS) - Compared between enzalutamide monotherapy versus placebo plus leuprolide.
Timepoint [4] 0 0
Up to approximately 67 months
Secondary outcome [5] 0 0
Time to prostate specific antigen (PSA) progression;
Timepoint [5] 0 0
Up to approximately 67 months
Secondary outcome [6] 0 0
Time to first use of new antineoplastic therapy
Timepoint [6] 0 0
Up to approximately 67 months
Secondary outcome [7] 0 0
Time to distant metastasis
Timepoint [7] 0 0
Up to approximately 67 months
Secondary outcome [8] 0 0
Proportion of patients per group who remain treatment free 2 years after suspension of study drug treatment at week 37 due to undetectable PSA
Timepoint [8] 0 0
From baseline (week 37) up to 67 months
Secondary outcome [9] 0 0
Proportion of patients per group with undetectable PSA 2 years after suspension of study drug treatment at week 37 due to undetectable PSA
Timepoint [9] 0 0
From baseline (week 37) up to 67 months
Secondary outcome [10] 0 0
Proportion of patients per group with undetectable PSA at 36 weeks on study drug
Timepoint [10] 0 0
At week 36
Secondary outcome [11] 0 0
Time to resumption of any hormonal therapy following suspension at week 37 due to undetectable PSA
Timepoint [11] 0 0
From baseline (week 37) up to 67 months
Secondary outcome [12] 0 0
Time to symptomatic progression
Timepoint [12] 0 0
Up to approximately 67 months
Secondary outcome [13] 0 0
Time to first symptomatic skeletal event
Timepoint [13] 0 0
Up to approximately 96 months
Secondary outcome [14] 0 0
Time to clinically relevant pain
Timepoint [14] 0 0
Up to approximately 67 months
Secondary outcome [15] 0 0
Quality of life via the Functional Assessment of Cancer Therapy Prostate (FACT P) questionnaire,
Timepoint [15] 0 0
Up to approximately 67 months
Secondary outcome [16] 0 0
Quality of life via the European Quality of Life 5 Dimensions 5 Levels Health Questionnaire (EQ 5D 5L),
Timepoint [16] 0 0
Up to approximately 67 months
Secondary outcome [17] 0 0
Quality of life via the Quality of Life Questionnaire Prostate 25 (QLQ PR25) module
Timepoint [17] 0 0
Up to approximately 67 months

Eligibility
Key inclusion criteria
- Histologically or cytologically confirmed adenocarcinoma of the prostate at initial
biopsy, without neuroendocrine differentiation, signet cell, or small cell features;

- Prostate cancer initially treated by radical prostatectomy or radiotherapy (including
brachytherapy) or both, with curative intent;

- PSA doubling time = 9 months;

- Screening PSA by the central laboratory = 1 ng/mL for patients who had radical
prostatectomy (with or without radiotherapy) as primary treatment for prostate cancer
and at least 2 ng/mL above the nadir for patients who had radiotherapy only as primary
treatment for prostate cancer;

- Serum testosterone = 150 ng/dL (5.2 nmol/L).
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior or present evidence of distant metastatic disease as assessed by radiographic
imaging;

- Prior hormonal therapy. Neoadjuvant/adjuvant therapy to treat prostate cancer = 36
months in duration and = 9 months before randomization, or a single dose or a short
course (= 6 months) of hormonal therapy given for rising PSA = 9 months before
randomization is allowed.;

- Prior cytotoxic chemotherapy, aminoglutethimide, ketoconazole, abiraterone acetate, or
enzalutamide for prostate cancer;

- Prior systemic biologic therapy, including immunotherapy, for prostate cancer;

- Major surgery within 4 weeks before randomization;

- Treatment with 5-a reductase inhibitors (finasteride, dutasteride) within 4 weeks of
randomization;

- Known or suspected brain metastasis or active leptomeningeal disease;

- History of another invasive cancer within 3 years before screening, with the exception
of fully treated cancers with a remote probability of recurrence

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,NEWQLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Genesis Cancer Care NSW - Gateshead
Recruitment hospital [2] 0 0
Lismore Base hospital - Lismore
Recruitment hospital [3] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [4] 0 0
Macquarie University - North Ryde
Recruitment hospital [5] 0 0
Genesis Cancer Care - North Sydney
Recruitment hospital [6] 0 0
Port Macquarie Base Hospital - Port Macquarie
Recruitment hospital [7] 0 0
Northern Cancer Institute - St Leonards
Recruitment hospital [8] 0 0
The Tweed Hospital - Tweed Heads
Recruitment hospital [9] 0 0
Australian Clinical Trials Pty Ltd - Wahroonga
Recruitment hospital [10] 0 0
Sydney Adventist Hospital - Wahroonga
Recruitment hospital [11] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [12] 0 0
Westmead Hospital - Westmead
Recruitment hospital [13] 0 0
Illawarra Cancer Care Centre - Wollongong
Recruitment hospital [14] 0 0
Crown Princess Mary Cancer Centre - Westmead
Recruitment hospital [15] 0 0
Icon Cancer Care Wesley - Auchenflower
Recruitment hospital [16] 0 0
Icon Cancer Care Chermside - Chermside
Recruitment hospital [17] 0 0
Icon Cancer Care South Brisbane - South Brisbane
Recruitment hospital [18] 0 0
Icon Cancer Foundation - South Brisbane
Recruitment hospital [19] 0 0
Icon Cancer Centre Southport - Southport
Recruitment hospital [20] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [21] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [22] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [23] 0 0
Austin Health - Heidelberg
Recruitment hospital [24] 0 0
Australian Urology Associates - Malvern
Recruitment hospital [25] 0 0
Sunshine Hospital - St Albans
Recruitment hospital [26] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
2290 - Gateshead
Recruitment postcode(s) [2] 0 0
2480 - Lismore
Recruitment postcode(s) [3] 0 0
2170 - Liverpool
Recruitment postcode(s) [4] 0 0
2109 - North Ryde
Recruitment postcode(s) [5] 0 0
2060 - North Sydney
Recruitment postcode(s) [6] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [7] 0 0
2065 - St Leonards
Recruitment postcode(s) [8] 0 0
2485 - Tweed Heads
Recruitment postcode(s) [9] 0 0
2076 - Wahroonga
Recruitment postcode(s) [10] 0 0
2298 - Waratah
Recruitment postcode(s) [11] 0 0
2145 - Westmead
Recruitment postcode(s) [12] 0 0
2500 - Wollongong
Recruitment postcode(s) [13] 0 0
4066 - Auchenflower
Recruitment postcode(s) [14] 0 0
4032 - Chermside
Recruitment postcode(s) [15] 0 0
4101 - South Brisbane
Recruitment postcode(s) [16] 0 0
4215 - Southport
Recruitment postcode(s) [17] 0 0
5000 - Adelaide
Recruitment postcode(s) [18] 0 0
3128 - Box Hill
Recruitment postcode(s) [19] 0 0
3168 - Clayton
Recruitment postcode(s) [20] 0 0
3084 - Heidelberg
Recruitment postcode(s) [21] 0 0
3144 - Malvern
Recruitment postcode(s) [22] 0 0
3021 - St Albans
Recruitment postcode(s) [23] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
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Alabama
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United States of America
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Alaska
Country [3] 0 0
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Arizona
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California
Country [5] 0 0
United States of America
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Colorado
Country [6] 0 0
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Connecticut
Country [7] 0 0
United States of America
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District of Columbia
Country [8] 0 0
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Florida
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United States of America
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Georgia
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United States of America
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Illinois
Country [11] 0 0
United States of America
State/province [11] 0 0
Indiana
Country [12] 0 0
United States of America
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Kansas
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United States of America
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Maryland
Country [14] 0 0
United States of America
State/province [14] 0 0
Michigan
Country [15] 0 0
United States of America
State/province [15] 0 0
Nebraska
Country [16] 0 0
United States of America
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Nevada
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United States of America
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New Jersey
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New York
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North Carolina
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Ohio
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Oklahoma
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Oregon
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Pennsylvania
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South Carolina
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Tennessee
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Texas
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Virginia
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Austria
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Upper Austria
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Austria
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Linz
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Austria
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Salzburg
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Austria
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Vienna
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RS
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Alberta
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Ontario
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Arhus N
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Copenhagen N
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Copenhagen
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Odense C
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Tampere
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Brest
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Lille cedex
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Montpellier cedex
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Nantes
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Paris cedex 10
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France
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Paris Cedex 14
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France
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Saint-Gregoire
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Suresnes
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France
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Villejuif cedex
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France
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Villejuif
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Cremona
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Faenza RA
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Lugo RA
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Italy
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Meldola (FC)
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Italy
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Napoli
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Italy
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Orbassano (TO)
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Italy
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Ravenna
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Italy
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Rimini
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Roma
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Trento
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Korea, Republic of
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Gyeonggi-do
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Gyeongsangnam-do
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Korea, Republic of
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Incheon
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Korea, Republic of
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Seoul
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Netherlands
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Amsterdam
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Ede
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Groningen
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Leeuwarden
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Maastricht
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Sneek
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Gdansk
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Slupsk
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Poland
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Torun
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Wroclaw
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Martin
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Nitra
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Presov
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Zilina
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Spain
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Barcelona
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Spain
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LA Coruna
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Cadiz
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Girona
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Madrid
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Spain
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Orense
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Spain
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Salamanca
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Spain
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Valencia
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Sweden
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Goteborg
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Sweden
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Malmo
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Sweden
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Orebro
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Sweden
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Stockholm
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Sweden
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Umea
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Sweden
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Uppsala
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Taiwan
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Kaohsiung
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Taiwan
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Taichung
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Taiwan
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Taipei
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Taiwan
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Taoyuan
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United Kingdom
State/province [118] 0 0
CITY OF Glasgow
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United Kingdom
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Devon
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United Kingdom
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Greater London
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United Kingdom
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Surrey
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United Kingdom
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WEST Midlands
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United Kingdom
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Bristol
Country [124] 0 0
United Kingdom
State/province [124] 0 0
Glasgow

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Pfizer
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Astellas Pharma Inc
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to assess enzalutamide plus leuprolide in patients with
high-risk nonmetastatic prostate cancer progressing after radical prostatectomy or
radiotherapy or both.
Trial website
https://clinicaltrials.gov/show/NCT02319837
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications