Safety and Efficacy Study of Enzalutamide Plus Leuprolide in Patients With Nonmetastatic Prostate Cancer (EMBARK)

• ClinicalTrials.gov Identifier: NCT02319837
• Recruitment Status: Active, not recruiting
• First Posted: December 18, 2014
• Results First Posted: March 25, 2024
• Last Update Posted: March 25, 2024
• Sponsor: Pfizer
• Collaborators: Astellas Pharma Inc; Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
• Information provided by (Responsible Party): Pfizer

Study Description

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.

The randomized / blinded portion of the study is now completed following primary endpoint analyses. The study remains ongoing in open label format.

Condition or disease	Intervention/treatment	Phase
Hormone Sensitive Prostate Cancer; Prostate Cancer; Cancer of the Prostate	Drug: Enzalutamide; Drug: Placebo (No longer applicable in Open Label study period); Drug: Leuprolide Open Label	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1068 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: The randomized blinded portion of the study has concluded. The study is now being conducted open label manner.
• Primary Purpose: Treatment
• Official 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
• Actual Study Start Date: December 17, 2014
• Actual Primary Completion Date: January 31, 2023
• Estimated Study Completion Date: September 19, 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Enzalutamide plus leuprolide; Enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily in combination with leuprolide administered as a single intramuscular or subcutaneous injection once every 12 weeks	Drug: Enzalutamide; Other Names: MDV3100; Xtandi; Drug: Leuprolide Open Label; Other Names: Eligard; Leuprolide Acetate; Leuprorelin; Lupron
Experimental: Enzalutamide monotherapy; Enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily	Drug: Enzalutamide; Other Names: MDV3100; Xtandi
Active Comparator: Leuprolide plus placebo; 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. The randomized blinded portion of the study has concluded following primary endpoint analyses. In the Open Label Period the placebo is no longer applicable in this study arm, and patients continue to receive leuprolide alone.	Drug: Placebo (No longer applicable in Open Label study period); Sugar pill to mimic enzalutamide

Outcome Measures

Primary Outcome Measures :

1. Metastasis-free Survival (MFS) Compared Between Enzalutamide Plus Leuprolide and Placebo Plus Leuprolide [ Time Frame: From randomization until radiographic progression or death without radiographic progression, whichever occurred first (up to Month 98 when at least 197 MFS events occurred among the 3 treatment groups) ]
   MFS was defined as the duration of time in months between randomization and the earliest objective evidence of radiographic progression by central imaging or death without radiographic progression, whichever occurred first. Radiographic progression for soft tissue disease was defined by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1). Radiographic progression for bone disease was defined as the appearance of 1 or more metastatic lesions on bone scan (a bone scan assesses 5 regions of the skeleton, including skull, thorax, spine, pelvis, and extremities). Confirmation with a second imaging modality (plain film, computed tomography [CT], or magnetic resonance imaging [MRI]) was to be required when bone lesions were found in a single region on the bone scan. Appearance of metastatic lesions in 2 or more of the 5 regions on a bone scan was not to require confirmation with a second imaging modality.

Secondary Outcome Measures :

1. Metastasis-free Survival (MFS) Compared Between Enzalutamide Monotherapy and Placebo Plus Leuprolide [ Time Frame: From randomization until radiographic progression or death without radiographic progression, whichever occurred first (up to Month 98 when at least 197 MFS events occurred among the 3 treatment groups) ]
   MFS was defined as the duration of time in months between randomization and the earliest objective evidence of radiographic progression by central imaging or death without radiographic progression, whichever occurred first. Radiographic progression for soft tissue disease was defined by RECIST 1.1. Radiographic progression for bone disease was defined as the appearance of 1 or more metastatic lesions on bone scan (a bone scan assesses 5 regions of the skeleton, including skull, thorax, spine, pelvis, and extremities). Confirmation with a second imaging modality (plain film, CT, or MRI) was to be required when bone lesions were found in a single region on the bone scan. Appearance of metastatic lesions in 2 or more of the 5 regions on a bone scan was not to require confirmation with a second imaging modality.
2. Time to Prostate-specific Antigen (PSA) Progression [ Time Frame: From randomization until first PSA progression (up to Month 98) ]
   Time to PSA progression was defined as the time in months from randomization to the date of the first PSA value demonstrating progression, while participants were on study treatment, which was subsequently confirmed at least 3 weeks later. PSA progression date was defined as the date that a ≥25% increase and an absolute increase of ≥2 micrograms per liter (μg/L) (2 nanograms per milliliter [ng/mL]) above the nadir (or baseline for participants with no PSA decline by Week 25) that was confirmed by a second consecutive value at least 3 weeks later. For participants who had suspended treatment at Week 37 and later reinitiated treatment, baseline was reset as the last PSA assessment prior to or on the date of reinitiation of treatment.
3. Time to First Use of New Antineoplastic Therapy [ Time Frame: From randomization until first use of new antineoplastic therapy (up to Month 98) ]
   Time to first use of new antineoplastic therapy was defined as the time in months from randomization to first use of new antineoplastic therapy for prostate cancer.
4. Overall Survival (OS) [ Time Frame: From randomization until death due to any cause (up to Month 98 when at least 197 MFS events occurred among the 3 treatment groups) ]
   Overall survival was defined as the time in months between randomization and death due to any cause.
5. Time to Distant Metastasis [ Time Frame: From randomization until the earliest objective evidence of distant soft tissue metastases or metastatic bone disease (up to Month 98) ]
   The time to distant metastasis was defined as the time in months from randomization to the earliest objective evidence of distant soft tissue metastases or metastatic bone disease by blinded independent central review (BICR).
6. Percentage of Participants With Undetectable Prostate-specific Antigen (PSA) at 36 Weeks on Study Drug [ Time Frame: At Week 36 ]
   Undetectable PSA at 36 weeks was serum PSA levels <0.2 ng/mL at Week 36. Percentage of participants with undetectable PSA at 36 weeks on study drug was calculated as the number of participants with undetectable PSA at Week 36 divided by the number of participants with PSA values at Week 36, and multiplied by 100.
7. Percentage of Participants Who Remained Treatment-free 2 Years After Suspension of Study Treatment at Week 37 Due to Undetectable Prostate-specific Antigen (PSA) [ Time Frame: From randomization until 2 years after Week 37 (up to Month 34) ]
   Undetectable PSA at 36 weeks was serum PSA levels <0.2 ng/mL at Week 36. At Week 37, study treatment was suspended for participants whose PSA values were undetectable (<0.2 ng/mL) at Week 36 as determined by the central laboratory. Study treatment may have been suspended only once (at Week 37) due to undetectable PSA and was reinitiated if subsequent central laboratory PSA values increased to ≥2.0 ng/mL for participants with prior prostatectomy or ≥5.0 ng/mL for participants without prostatectomy. Percentage of participants who remained treatment-free 2 years after suspension of study treatment at Week 37 was calculated as the number of participants who remained treatment-free 2 years after suspension of study treatment at Week 37 divided by the number of participants with treatment suspension and multiplied by 100.
8. Percentage of Participants With Undetectable Prostate-specific Antigen (PSA) 2 Years After Suspension of Treatment at Week 37 Due to Undetectable PSA [ Time Frame: From randomization until 2 years after Week 37 (up to Month 34) ]
   Undetectable PSA at 36 weeks was serum PSA levels <0.2 ng/mL at Week 36. At Week 37, study treatment was suspended for participants whose PSA values were undetectable (<0.2 ng/mL) at Week 36 as determined by the central laboratory. Study treatment may have been suspended only once (at Week 37) due to undetectable PSA and was reinitiated if subsequent central laboratory PSA values increased to ≥2.0 ng/mL for participants with prior prostatectomy or ≥5.0 ng/mL for participants without prostatectomy. Percentage of participants with undetectable PSA 2 years after suspension of treatment at Week 37 due to undetectable PSA was calculated as the number of participants with undetectable PSA 2 years after suspension of treatment at Week 37 due to undetectable PSA divided by the number of participants with treatment suspension and multiplied by 100.
9. Time to Resumption of Any Hormonal Therapy Following Suspension at Week 37 Due to Undetectable Prostate-specific Antigen (PSA) [ Time Frame: From treatment suspension at Week 37 until resumption of any hormonal therapy (up to Month 98) ]
   Undetectable PSA at 36 weeks was serum PSA levels <0.2 ng/mL at Week 36. At Week 37, study treatment was suspended for participants whose PSA values were undetectable (<0.2 ng/mL) at Week 36 as determined by the central laboratory. Study treatment may have been suspended only once (at Week 37) due to undetectable PSA and was reinitiated if subsequent central laboratory PSA values increased to ≥2.0 ng/mL for participants with prior prostatectomy or ≥5.0 ng/mL for participants without prostatectomy. The time to resumption of any hormonal therapy following suspension at Week 37 due to undetectable PSA was defined as the time in months between the date of treatment suspension at Week 37 due to undetectable PSA and the date that hormonal therapy was restarted.
10. Time to Castration Resistance [ Time Frame: From randomization to the first occurrence of radiographic disease progression, PSA progression or SSE, whichever occurred first with castrate levels of testosterone (up to Month 98) ]
    Time to castration resistance applied only to participants receiving leuprolide treatment and was defined as the time in months from randomization to the first occurrence of radiographic disease progression by BICR, PSA progression or symptomatic skeletal event (SSE) whichever occurred first with castrate levels of testosterone (<50 ng/dL).
11. Time to Symptomatic Progression [ Time Frame: From randomization until the first development of events defined as symptomatic progression (up to Month 98) ]
    Time to symptomatic progression was defined as the time in months from randomization to development of a skeletal-related event, worsening of disease-related symptoms requiring initiation of a new antineoplastic therapy, or development of adverse events (AEs) and clinically significant signs and/or symptoms due to loco-regional tumor progression requiring opiate use, surgical intervention or radiation therapy, whichever occurred first.
12. Time to First Symptomatic Skeletal Event (SSE) [ Time Frame: From randomization until the first development of events defined as SSE (up to Month 98) ]
    Time to first symptomatic skeletal event was defined as the time in months from randomization to use of radiation therapy (external beam radiation therapy or radionuclides) or surgery to bone for prostate cancer, findings of clinically apparent pathologic bone fracture or of spinal cord compression, or new use of opiate and/or systemic antineoplastic therapy due to bone pain collected in the SSE case report form (CRF), whichever occurred first.
13. Time From Randomization to Onset of Clinically Relevant Pain Progression, Defined as a 2-point or Greater Increase From Baseline in the Brief Pain Inventory-Short Form (BPI-SF) Question 3 Score [ Time Frame: From randomization until a 2-point or greater increase from baseline in the BPI-SF question 3 score (up to Month 98) ]
    Time to clinically relevant pain progression was defined as the time from randomization to onset of pain progression, where clinically relevant pain progression was defined as a 2-point or greater increase from baseline in the BPI-SF question 3 score. BPI-SF is a self-administered questionnaire containing 9 main questions related to pain and analgesic medication use, where question 3 (paraphrased) is "On a scale of 0 [no pain] to 10 [pain as bad as you can imagine], please rate your pain at its worst in the last 24 hours" with higher score indicating worse pain.
14. Time From Randomization to First Assessment With at Least a 10-point Decline (Deterioration) From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score [ Time Frame: From randomization to first assessment with at least a 10-point decrease from baseline in the FACT-P total score (up to Month 98) ]
    Time to first deterioration of the FACT-P total score was defined as the time from randomization to first assessment with at least a 10-point decrease from baseline in the FACT-P total score. FACT-P total score is based on subscale scores of physical, social/family, emotional, and functional well-being, as well as 12 site-specific items to assess prostate-related symptoms, ranging 0-156, with higher score representing better quality of life.
15. Number of Participants With Treatment-emergent Adverse Events (TEAEs) (All-causality) During On-treatment Period, Modified Treatment Period, and Treatment Reinitiation Period - at PCD Cut-off Date of 31 January 2023 [ Time Frame: From first dose of study drug to the last dose + 30 days, or the day before initiation of a new antineoplastic treatment (up to Month 98) ]
    An AE was any untoward medical occurrence (eg, sign, symptom, illness, disease or injury) in a participant administered study drug or other protocol-imposed intervention, regardless of attribution. TEAEs were those events with onset dates occurring during the on-treatment period for the first time. On-treatment period was the time from the date of first dose of study treatment through a minimum of 30 days after last dose of study treatment, or the start day of new antineoplastic drug therapy minus 1 day. Modified TEAEs (mTEAEs) were AEs that occurred during the modified treatment period (events occurring or worsening during the treatment suspension period after 30 days of last dose prior to treatment suspension were excluded). Reinitiated TEAEs (rTEAEs) were AEs that occurred with a start date during the dosing period after suspension and reinitiation of study treatment as defined by the reinitiation treatment period.
16. Number of Participants With Grade 3 or Higher Treatment-emergent Adverse Events (TEAEs) (All-causality) - at PCD Cut-off Date of 31 January 2023 [ Time Frame: From first dose of study drug to the last dose + 30 days, or the day before initiation of a new antineoplastic treatment (up to Month 98) ]
    An AE was any untoward medical occurrence (e.g., sign, symptom, illness, disease or injury) in a participant administered study drug or other protocol-imposed intervention, regardless of attribution. TEAEs were those events with onset dates occurring during the on-treatment period for the first time. On-treatment period was defined as the time from the date of first dose of study treatment through a minimum of 30 days after last dose of study treatment, or the start day of new antineoplastic drug therapy minus 1 day. The severity of all TEAEs was evaluated by the investigator based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03: grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (potentially life-threatening) and grade 5 (death related to AE).
17. Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Treatment-related) During On-treatment Period, Modified Treatment Period, and Treatment Reinitiation Period - at PCD Cut-off Date of 31 January 2023 [ Time Frame: From first dose of study drug to the last dose + 30 days, or the day before initiation of a new antineoplastic treatment (up to Month 98) ]
    An AE was any untoward medical occurrence (eg, sign, symptom, illness, disease or injury) in a participant administered study drug or other protocol-imposed intervention, regardless of attribution. TEAEs were those with onset dates occurring during the on-treatment period for the first time. On-treatment period was the time from date of first dose of study treatment through at least 30 days after last dose of study treatment or start day of new antineoplastic drug therapy minus 1 day. Treatment-related TEAEs were TEAEs attributed to study drug (enzalutamide, placebo or leuprolide). mTEAEs were AEs that occurred during the modified treatment period (events occurring or worsening during the treatment suspension period after 30 days of last dose prior to treatment suspension were excluded). rTEAEs were AEs that occurred with a start date during the dosing period after suspension and reinitiation of study treatment (reinitiation treatment period).
18. Number of Participants With SAEs (All-causality) During On-treatment Period, Modified Treatment Period and Treatment Reinitiation Period and SAEs (Treatment-related) During On-treatment period-at PCD Cut-off 31 Jan 2023 [ Time Frame: From first dose of study drug to the last dose + 30 days, or the day before initiation of a new antineoplastic treatment (up to Month 98) ]
    An AE was any untoward medical occurrence in a participant administered study drug/other protocol-imposed intervention regardless of attribution. SAEs were AEs resulting in any of the following outcomes/deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent/significant disability/incapacity; congenital anomaly. On-treatment period was time from first dose date of study treatment through ≥30 days after last dose of study treatment or start day of new antineoplastic drug therapy -1 day. mSAEs were SAEs occurring during modified treatment period (events occurring/worsening during treatment suspension period after 30 days of last dose prior to treatment suspension were excluded). rSAEs were SAEs occurring with a start date during the dosing period after suspension and reinitiation of study treatment. Treatment-related SAEs were attributed to any study drug.
19. Number of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Enzalutamide or Placebo Discontinuation - at PCD Cut-off Date of 31 January 2023 [ Time Frame: From first dose of study drug to the last dose + 30 days, or the day before initiation of a new antineoplastic treatment (up to Month 98) ]
    An AE was any untoward medical occurrence (eg, sign, symptom, illness, disease or injury) in a participant administered study drug or other protocol-imposed intervention, regardless of attribution. TEAEs were those events with onset dates occurring during the on-treatment period for the first time. On-treatment period was the time from the date of first dose of study treatment through a minimum of 30 days after last dose of study treatment, or the start day of new antineoplastic drug therapy minus 1 day.
20. Number of Participants With Shifts From Grade ≤2 at Baseline to Grade 3 or Grade 4 Post-baseline in Hematology Laboratory Test Values - at PCD Cut-off Date of 31 January 2023 [ Time Frame: From first dose of study drug to the last dose + 30 days, or the day before initiation of a new antineoplastic treatment (up to Month 98) ]
    Participants who experienced hematology laboratory test abnormalities were summarized according to worst toxicity grade observed for each hematology laboratory test. Hematology laboratory abnormalities were graded according to CTCAE version 4.03 (Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death). This outcome measure calculated the number of participants with hematology laboratory abnormalities that were shifted from ≤Grade 2 at baseline to Grade 3 and Grade 4 post-baseline for the following parameters: hemoglobin, leukocytes, lymphocytes, neutrophils, platelets.
21. Number of Participants With Shifts From Grade ≤2 at Baseline to Grade 3 or Grade 4 Post-baseline in Chemistry Laboratory Test Values - at PCD Cut-off Date of 31 January 2023 [ Time Frame: From first dose of study drug to the last dose + 30 days, or the day before initiation of a new antineoplastic treatment (up to Month 98) ]
    Participants who experienced chemistry laboratory test abnormalities were summarized according to worst toxicity grade observed for each chemistry laboratory test. Chemistry laboratory abnormalities were graded according to CTCAE version 4.03 (Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death). This outcome measure calculated the number of participants with chemistry laboratory abnormalities that were shifted from ≤Grade 2 at baseline to Grade 3 and Grade 4 post-baseline for the following parameters: alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, calcium, creatine kinase, glucose, magnesium, phosphate, potassium, sodium.
22. Number of Participants With Potentially Clinically Significant Vital Signs - at PCD Cut-off Date of 31 January 2023 [ Time Frame: From first dose of study drug to the last dose + 30 days, or the day before initiation of a new antineoplastic treatment (up to Month 98) ]
    Participants with potentially clinically significant abnormalities in vital signs were summarized for the following parameters: systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR). Potentially clinically significant abnormalities were defined as (1) SBP (mmHg): >180 and increase from baseline >40; <90 and decrease from baseline >30; final visit or 2 consecutive visits change from baseline (CFB) ≥10, ≥15, ≥20; final visit or most extreme result ≥140, ≥180, ≥140 and ≥20 CFB, ≥180 and ≥20 CFB; (2) DBP (mmHg): >105 and increase from baseline >30; <50 and decrease from baseline >20; final visit or 2 consecutive visits CFB ≥5, ≥10, ≥15; final visit or most extreme result ≥90, ≥105, ≥90 and ≥15 CFB, ≥105 and ≥15 CFB; (3) HR (bpm): >120 and increase from baseline >30; <50 and decrease from baseline >20.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: No

Criteria

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).

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-α 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

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35233

University of Alabama at Birmingham, IDS Pharmacy

Birmingham, Alabama, United States, 35249

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35249

United States, Alaska

Alaska Urological Institute dba Alaska Clinical Research Center

Anchorage, Alaska, United States, 99503

United States, Arizona

Urological Associates of Southern Arizona, PC

Tucson, Arizona, United States, 85741

United States, California

Tower Hematology Oncology Medical Group

Beverly Hills, California, United States, 90211

Cedars-Senai OCC Pharmacy

Los Angeles, California, United States, 90048

Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute

Los Angeles, California, United States, 90048

University of California, Irvine Medical Center

Orange, California, United States, 92868

Sutter Medical Group, Vascular & Varicose Vein Center

Roseville, California, United States, 95661

Sutter Medical Group

Roseville, California, United States, 95661

UC Davis Comprehensive Cancer Center

Sacramento, California, United States, 95817

University of California Davis Medical Center

Sacramento, California, United States, 95817

University of California, Davis, School of Medicine

Sacramento, California, United States, 95817

United States, Colorado

The Urology Center of Colorado

Denver, Colorado, United States, 80211

Foothills Urology, P.C.

Golden, Colorado, United States, 80401

United States, Connecticut

Eastern Connecticut Hematology Oncology Associates

Norwich, Connecticut, United States, 06360

United States, District of Columbia

Johns Hopkins Kimmel Cancer Center/ Sibley Infusion

Washington, District of Columbia, United States, 20016

United States, Florida

Lakeland Regional Health Hollis Cancer Center

Lakeland, Florida, United States, 33805

United States, Georgia

Emory University Hospital

Atlanta, Georgia, United States, 30322

Investigational Drug Service

Atlanta, Georgia, United States, 30322

The Emory Clinic

Atlanta, Georgia, United States, 30322

Winship Cancer Institute, Emory University

Atlanta, Georgia, United States, 30322

United States, Illinois

Northwestern Medical Group

Chicago, Illinois, United States, 60611

Northwestern Memorial Hospital

Chicago, Illinois, United States, 60611

United States, Indiana

First Urology, PSC

Jeffersonville, Indiana, United States, 47130

United States, Kansas

The University of Kansas Hospital

Kansas City, Kansas, United States, 66160

Kansas City Urology Care, PA

Overland Park, Kansas, United States, 66211-1231

The University of Kansas Cancer Center and Medical Pavilion

Westwood, Kansas, United States, 66205

The University of Kansas Cancer Center, Investigational Drug Services

Westwood, Kansas, United States, 66205

GU Research Network/Wichita Urology Group

Wichita, Kansas, United States, 67226

United States, Maryland

John Hopkins University Hospital

Baltimore, Maryland, United States, 21287

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States, 21287

The Sidney Kimmel Cancer Center at Johns Hopkins Hospital- Oncology Investigational Drug Services

Baltimore, Maryland, United States, 21287

Chesapeake Urology Research Associates

Towson, Maryland, United States, 21204

United States, Michigan

Comprehensive Urology - Macomb Office

Macomb, Michigan, United States, 48044

Comprehensive Urology - Royal Oak (Stephenson) office

Royal Oak, Michigan, United States, 48067

United States, Nebraska

GU Research Network, LLC / Urology Cancer Center

Omaha, Nebraska, United States, 68130

United States, Nevada

VA Lahontan Valley Outpatient Clinic

Fallon, Nevada, United States, 89406

United States, New Jersey

Memorial Sloan Kettering Cancer Center Basking Ridge

Basking Ridge, New Jersey, United States, 07920

United States, New York

Memorial Sloan Kettering Cancer Center Commack

Commack, New York, United States, 11725

Memorial Sloan Kettering Cancer Center Westchester

Harrison, New York, United States, 10604

Memorial Hospital

New York, New York, United States, 10065

Sidney Kimmel Center for Prostate and Urologic Cancers

New York, New York, United States, 10065

Premier Medical Group of the Hudson Valley PC

Poughkeepsie, New York, United States, 12603

Memorial Sloan Kettering Cancer Center Rockville Centre

Rockville Centre, New York, United States, 11570

Associated Medical Professionals of New York, PLLC

Syracuse, New York, United States, 13210

Memorial Sloan Kettering Cancer Center Nassau

Uniondale, New York, United States, 11553

United States, North Carolina

Duke Investigational Chemotherapy Services

Durham, North Carolina, United States, 27710

Duke Nuclear Medicine

Durham, North Carolina, United States, 27710

Duke University Medical Center

Durham, North Carolina, United States, 27710

Alliance Urology Specialists, PA

Greensboro, North Carolina, United States, 27403

United States, Ohio

TriState Urologic Services PSC Inc., dba The Urology Group

Cincinnati, Ohio, United States, 45212

Mercy Health Jewish Hospital

Cincinnati, Ohio, United States, 45236

Clinical Research Solutions

Middleburg Heights, Ohio, United States, 44130

Southwest Urology

Middleburg Heights, Ohio, United States, 44130

United States, Oklahoma

OU Medical Center Presbyterian Tower

Oklahoma City, Oklahoma, United States, 73104

Stephenson Cancer Center

Oklahoma City, Oklahoma, United States, 73104

Stephenson Cancer Center

Oklahoma City, Oklahoma, United States, 73140

United States, Oregon

Oregon Imaging Center

Eugene, Oregon, United States, 97401

Oregon Urology Institute

Springfield, Oregon, United States, 97477

United States, Pennsylvania

Urologic Consultants of SE PA

Bala-Cynwyd, Pennsylvania, United States, 19004

Keystone Urology Specialists

Lancaster, Pennsylvania, United States, 17604

Lancaster Urology

Lancaster, Pennsylvania, United States, 17604

Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization

Philadelphia, Pennsylvania, United States, 19083

Jefferson Medical Oncology

Philadelphia, Pennsylvania, United States, 19107

Jefferson Urology Associates

Philadelphia, Pennsylvania, United States, 19107

Thomas Jefferson University Hospital, Bodine Buiding

Philadelphia, Pennsylvania, United States, 19107

Thomas Jefferson University, Medical Oncology

Philadelphia, Pennsylvania, United States, 19107

Thomas Jefferson University, Sidney Kimmel Cancer Center

Philadelphia, Pennsylvania, United States, 19107

United States, South Carolina

Carolina Urologic Research Center

Myrtle Beach, South Carolina, United States, 29572

United States, Tennessee

Vanderbilt Unversity Medical Center, Dept. of Urologic Surgery

Nashville, Tennessee, United States, 37232

Vanderbilt Unversity Medical Center, The Urology Clinic

Nashville, Tennessee, United States, 37232

United States, Texas

Urology Clinics of North Texas, PLLC

Dallas, Texas, United States, 75231

Houston Metro Urology

Houston, Texas, United States, 77027

Urology San Antonio Research

San Antonio, Texas, United States, 78229

United States, Virginia

Henrico Doctor's Hospital

Henrico, Virginia, United States, 23229

Virginia Urology

Richmond, Virginia, United States, 23235

Urology of Virginia, PLLC.

Virginia Beach, Virginia, United States, 23462

Australia, New South Wales

Genesis Cancer Care NSW

Gateshead, New South Wales, Australia, 2290

Lismore Base hospital

Lismore, New South Wales, Australia, 2480

Liverpool Hospital

Liverpool, New South Wales, Australia, 2170

Macquarie University

North Ryde, New South Wales, Australia, 2109

Genesis Cancer Care

North Sydney, New South Wales, Australia, 2060

Port Macquarie Base Hospital

Port Macquarie, New South Wales, Australia, 2444

GenesisCare North Shore

St Leonards, New South Wales, Australia, 2065

The Tweed Hospital

Tweed Heads, New South Wales, Australia, 2485

Australian Clinical Trials Pty Ltd

Wahroonga, New South Wales, Australia, 2076

Sydney Adventist Hospital

Wahroonga, New South Wales, Australia, 2076

Calvary Mater Newcastle

Waratah, New South Wales, Australia, 2298

Westmead Hospital

Westmead, New South Wales, Australia, 2145

Illawarra Cancer Care Centre

Wollongong, New South Wales, Australia, 2500

Australia, NEW

Crown Princess Mary Cancer Centre

Westmead, NEW, Australia, 2145

Australia, Queensland

Icon Cancer Care Wesley

Auchenflower, Queensland, Australia, 4066

Icon Cancer Care Chermside

Chermside, Queensland, Australia, 4032

Icon Cancer Care South Brisbane

South Brisbane, Queensland, Australia, 4101

Icon Cancer Foundation

South Brisbane, Queensland, Australia, 4101

Icon Cancer Centre Southport

Southport, Queensland, Australia, 4215

Australia, South Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia, 5000

Australia, Victoria

Box Hill Hospital

Box Hill, Victoria, Australia, 3128

Monash Medical Centre

Clayton, Victoria, Australia, 3168

Austin Health

Heidelberg, Victoria, Australia, 3084

Australian Urology Associates

Malvern, Victoria, Australia, 3144

Sunshine Hospital

St Albans, Victoria, Australia, 3021

Australia, Western Australia

Fiona Stanley Hospital

Murdoch, Western Australia, Australia, 6150

Austria

Hospital Barmherzige Schwestern Linz

Linz, Upper Austria, Austria, 4010

Hospital Barmherzige Schwestern Linz, Department of Urology

Linz, Austria, 4010

Ordensklinikum Linz GmbH

Linz, Austria, 4020

Department of Nuclear Medicine and Endocrinology, University Hospital Salzburg, Austria

Salzburg, Austria, 5020

Department of Radiology, University Hospital Salzburg, Austria

Salzburg, Austria, 5020

Department of Urology,Paracelsus Medical University Salzburg

Salzburg, Austria, 5020

AKH - Medizinische Universität Wien

Vienna, Austria, 1090

Department of Internal Medicine I, Medical university Vienna

Vienna, Austria, 1090

Brazil

Hospital São Rafael S.A

Salvador, BA, Brazil, 41253-190

Liga Paranaense de Combate ao Cancer - Hospital Erasto Gaertner

Curitiba, Parana, Brazil, 81520-060

CITO - Centro Integrado de Terapia Onco-Hematologica - Hospital de Clinicas de Passo Fundo

Passo Fundo, RS, Brazil, 99010-260

Hospital de Clinicas de Porto Alegre

Porto Alegre, RS, Brazil, 90035-903

CLINIONCO - Clinica de Oncologia de Porto Alegre Ltda.

Porto Alegre, RS, Brazil, 90430-090

Hospital Sao Lucas da PUCRS

Porto Alegre, RS, Brazil, 90610-0000

Fundacao Pio XII - Hospital de Cancer de Barretos

Barretos, SP, Brazil, 14784-400

Hospital das Clinicas da Faculdade de Ciencias Medicas da UNICAMP

Campinas, SP, Brazil, 13083-970

Centro de Estudos e Pesquisas de Hematologia e Oncologia - Faculdade de Medicina do ABC

Santo Andre, SP, Brazil, 09060-650

Oncosite - Centro de Pesquisa Clinica em Oncologia Ltda

Ijuí/RS, Brazil, 98700-000

Canada, Alberta

Prostate Cancer Centre

Calgary, Alberta, Canada, T2V 1P9

Cross Cancer Institute

Edmonton, Alberta, Canada, T6G 1Z2

Canada, British Columbia

Vancouver Prostate Centre

Vancouver, British Columbia, Canada, V5Z 1M9

Canada, Manitoba

Manitoba Prostate Centre CancerCare Manitoba

Winnipeg, Manitoba, Canada, R3E 0V9

Canada, Nova Scotia

Nova Scotia Health Authority

Halifax, Nova Scotia, Canada, B3H 2Y9

Canada, Ontario

The Male/Female Health and Research Centre, Royal Court Medical Centre

Barrie, Ontario, Canada, L4M 7G1

Kingston General Hospital

Kingston, Ontario, Canada, K7L 2V7

Centre for Applied Urological Research

Kingston, Ontario, Canada, K7L 3J7

Hotel Dieu Hospital

Kingston, Ontario, Canada, K7L 5G2

Urology Associates/ Urologic Medical Research

Kitchener, Ontario, Canada, N2N 2B9

London Health Sciences Centre - Victoria Hospital

London, Ontario, Canada, N6A 5W9

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada, M4N 3M5

University Health Network - Princess Margaret Cancer Centre

Toronto, Ontario, Canada, M5G 2M9

Canada, Quebec

Urology South Shore Research

Greenfield Park, Quebec, Canada, J4V 2H3

Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, Canada, H2X 3E4

McGill University Health Centre

Montreal, Quebec, Canada, H4A 3J1

Ultra-Med Inc.

Pointe-Claire, Quebec, Canada, H9R 4S3

Canada

CHU de Quebec - L'Hotel-Dieu de Quebec

Quebec, Canada, G1R 2J6

CHU de Quebec - L'Hotel-Dieu de Quebec - CRCEO

Quebec, Canada, G1R 3S1

Denmark

Aarhus University Hospital

Arhus N, Denmark, 8200

Rigshospitalet - Copenhagen University Hospital

Copenhagen N, Denmark, 2200

Rigshospitalet - Copenhagen University Hospital

Copenhagen, Denmark, 2100

Rigshospitalet, Dept of Radiology

Copenhagen, Denmark, 2100

Odense University Hospital

Odense C, Denmark, 5000

Vejle Sygehus

Vejle, Denmark, 7100

Finland

Helsingin yliopistollinen keskussairaala

Helsinki, Finland, 00290

Oulun yliopistollinen sairaala

Oulu, Finland, 90220

Satakunnan Keskussairaala

Pori, Finland, 28500

Seinaejoen Keskussairaala

Seinaejoki, Finland, 60220

Tampereen yliopistollinen sairaala

Tampere, Finland, 33520

France

ICO- site Paul Papin

Angers cedex 09, France, 49933

Clinique Pasteur - Lanroze Service Pharmacie

Brest, France, 29200

Clinique Pasteur - Lanroze

Brest, France, 29200

CHD Vendée

LA ROCHE SUR YON cedex 9, France, 85925

CHRU de Lille - Hopital Claude Huriez

Lille cedex, France, 59037

ICM Val d'Aurelle

Montpellier Cedex 5, France, 34298

CHU de Nantes - Hotel Dieu

Nantes, France, 44000

Hopital Saint-Louis

Paris cedex 10, France, 75475

Institut Mutualiste Montsouris

Paris Cedex 14, France, 75674

CHP Saint-Gregoire

Saint-Gregoire, France, 35760

ICO - site Rene Gauducheau

Saint-Herblain cedex, France, 44805

Hia Begin

Saint-Mande, France, 94160

Hopital Foch

Suresnes, France, 92151

Institut Gustave Roussy

Villejuif cedex, France, 94805

Institut Gustave Roussy

Villejuif, France, 94800

Italy

Farmacia, Azienda Socio Sanitaria Territoriale di Cremona

Cremona, Italy, 26100

Struttura Complessa di Oncologia, Azienda Socio Sanitaria Territoriale di Cremona

Cremona, Italy, 26100

UO di Radiologia, Azienda Socio Sanitaria Territoriale di Cremona

Cremona, Italy, 26100

UO di Oncologia,Ospedale Civile degli Infermi

Faenza RA, Italy, 48018

UO di Radiologia, Ospedale Civile degli Infermi

Faenza RA, Italy, 48018

UO di Oncologia, Ospedale Civile Umberto I

Lugo RA, Italy, 48022

Uo di Radiologia, Ospedale Civile Umberto I

Lugo RA, Italy, 48022

Laboratorio Farmaci Antiblastici, IRCCS Istituto

Meldola (FC), Italy, 47014

U.O. Oncologia Medica, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola (FC), Italy, 47014

UO Radiologia,IRCCS Istituto Scientifico Romagnolo Per lO Studio e la Cura dei Tumori (IRST)

Meldola (FC), Italy, 47014

Istituto Nazionale Tumori Fondazione G. Pascale/Oncologia Medica A

Napoli, Italy, 80131

S.C.D.U. Oncologia Medica, A.O.U. San Luigi Gonzaga

Orbassano (TO), Italy, 10043

S.C.D.U. Radiodiagnostica, A.O.U. San Luigi Gonzaga

Orbassano (TO), Italy, 10043

Servizio di Farmacia, Ospedale Santa Maria delle Croci

Ravenna, Italy, 48121

Servizio di Radiologia, Ospedale Santa Maria Delle Croci

Ravenna, Italy, 48121

UO di Oncologia Medica, Ospedale Santa Maria delle Croci

Ravenna, Italy, 48121

Farmacia Interna, Ospedale degli Infermi

Rimini, Italy, 47923

UO Oncologia, Ospedale degli Infermi

Rimini, Italy, 47923

Azienda Ospedaliera S, Camillo Forlanini, UOC per il governo clinico in Oncologia Medica,pad,Flajani

Roma, Italy, 00152

U.O. di Oncologia Medica, Ospedale Santa Chiara

Trento, Italy, 38122

U.O. Medicina Nucleare, Ospedale Santa Chiara

Trento, Italy, 38122

U.O. Radiologia, Ospedale Santa Chiara

Trento, Italy, 38122

Korea, Republic of

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620

Pusan National University Yangsan Hospital

Yangsan-si, Gyeongsangnam-do, Korea, Republic of, 50612

Chonnam National University Hwasun Hospital

Hwasun-gun, Jeollanam-do, Korea, Republic of, 58128

Gachon University Gil Medical Center

Incheon, Korea, Republic of, 21565

Severance Hospital. Yonsei University Health System

Seoul, Korea, Republic of, 03722

Asan Medical Center

Seoul, Korea, Republic of, 05505

Gangnam Severance Hospital, Yonsei University Health System

Seoul, Korea, Republic of, 06273

Samsung Medical Center

Seoul, Korea, Republic of, 06351

Netherlands

VU Medical Centrum, Department of Urology

Amsterdam, Netherlands, 1081 HV

Academisch Medisch Centrum

Amsterdam, Netherlands, 1105AZ

Gelderse Vallei Ziekenhuis

Ede, Netherlands, 6710 HN

Catharina Ziekenhuis Eindhoven

Eindhoven, Netherlands, 5623 EJ

University Medical Centrum Groningen, Department Urologie

Groningen, Netherlands, 9713 GZ

Medisch Centrum Leeuwarden

Leeuwarden, Netherlands, 8934 AD

Maastricht University Medical Center, Department of Urology

Maastricht, Netherlands, 6229 HX

Antonius Ziekenhuis

Sneek, Netherlands, 8601 ZK

Poland

Uniwersyteckie Centrum Kliniczne Klinika Onkologii i Radioterapii

Gdansk, Poland, 80-952

Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku Sp. z o. o.

Slupsk, Poland, 76-200

Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku Sp. z o.o., Oddzial Urologiczny

Slupsk, Poland, 76-200

Kujawsko-Pomorskie Centrum Urologicznw Sp z o.o

Torun, Poland, 87-100

Centrum Medyczne Melita Medical

Wroclaw, Poland, 50-449

EMC Instytut Medyczny Spolka Akcyjna

Wroclaw, Poland, 54-144

Slovakia

Fakultna nemocnica s poliklinikou F.D.Roosevelta

Banska Bystrica, Slovakia, 975 17

CUIMED, s.r.o., Urologicka ambulancia

Bratislava, Slovakia, 851 05

Vychodoslovensky onkologicky ustav, a.s.

Kosice, Slovakia, 041 91

Univerzitna nemocnica Martin

Martin, Slovakia, 036 59

UROEXAM, spol. s r.o.

Nitra, Slovakia, 949 01

MILAB

Presov, Slovakia, 080 81

Fakultna nemocnica s poliklinikou Zilina

Zilina, Slovakia, 012 07

Spain

Althaia, Xarxa Assistencial Universitària de Manresa

Manresa, Barcelona, Spain, 08243

Hospital Universitari Son Espases

Palma de Mallorca, Islas Baleares, Spain, 07010

Complejo Hospitalario Universitario de Santiago

Santiago de Compostela, LA Coruna, Spain, 15706

Hospital del Mar

Barcelona, Spain, 08003

Hospital Clinic i Provincial de Barcelona, Dr. Antonio Alcaraz Asensio

Barcelona, Spain, 08036

Hospital Universitario Puerta del Mar

Cadiz, Spain, 11009

ICO Girona; Hospital Universitari de Girona Dr. Josep Trueta. Servicio de Oncologia

Girona, Spain, 17007

Hospital Universitario de La Princesa

Madrid, Spain, 28006

Hospital General Universitario Gregorio Maranon. Servicio de Oncologia.

Madrid, Spain, 28007

Centro Oncologico MD Anderson International Espana

Madrid, Spain, 28033

Hospital Universitario Ramon Y Cajal

Madrid, Spain, 28034

Hospital Universitario 12 de Octubre

Madrid, Spain, 28041

Althaia, Xarxa Assistencial Universitària de Manresa

Manresa, Spain, 08243

Complejo Hospitalario Universitario de Orense

Orense, Spain, 32005

Corporacio Sanitaria Parc Tauli

Sabadell, Spain, 08208

Hospital Clinico Universitario de Salamanca

Salamanca, Spain, 37007

Instituto Valenciano de Oncologia IVO

Valencia, Spain, 46009

Sweden

Sahlgrenska Universitetssjukhuset, Sahlgrenska

Goteborg, Sweden, 413 45

Skanes Universitetssjukhus

Malmo, Sweden, 205 02

Universitetssjukhuset Orebro

Orebro, Sweden, 70 185

Sodersjukhuset AB

Stockholm, Sweden, 118 83

Karolinska Universitetssjukhuset Solna

Stockholm, Sweden, 17176

Norrlands Universitetssjukhus

Umea, Sweden, 90 185

Norrlands Universitetssjukhus

Umea, Sweden, 90185

Akademiska Sjukhuset

Uppsala, Sweden, 751 85

Taiwan

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung, Taiwan, 807

China Medical University Hospital

Taichung, Taiwan, 40447

Taichung Veterans General Hospital

Taichung, Taiwan, 40705

National Taiwan University Hospital

Taipei, Taiwan, 10002

Chang Gung Memorial Hospital, Linkou

Taoyuan, Taiwan, 333

United Kingdom

Ross Hall Hospital

Glasgow, CITY OF Glasgow, United Kingdom, G52 3NQ

Royal Devon & Exeter Hospital

Wonford, Exeter, Devon, United Kingdom, EX2 5DW

Royal Free Hospital

London, Greater London, United Kingdom, NW3 2QG

The Royal Marsden NHS Foundation Trust

Sutton, Surrey, United Kingdom, SM2 5PT

Cancer Centre, Queen Elizabeth Hospital

Birmingham, WEST Midlands, United Kingdom, B15 2TH

University Hospitals Bristol NHS Foundation Trust

Bristol, United Kingdom, BS2 8ED

Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom, G12 OYN

Sponsors and Collaborators

Pfizer

Astellas Pharma Inc

Medivation LLC, a wholly owned subsidiary of Pfizer Inc.

Investigators

• Study Director: Pfizer Pfizer CT.gov Call Center; Pfizer

  Study Documents (Full-Text)

Documents provided by Pfizer:

Study Protocol  [PDF] May 18, 2023

Statistical Analysis Plan  [PDF] June 2, 2023

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Freedland SJ, De Giorgi U, Gleave M, Rosbrook B, Shen Q, Sugg J, Haas GP, Shore ND. A phase 3 randomised study of enzalutamide plus leuprolide and enzalutamide monotherapy in high-risk non-metastatic hormone-sensitive prostate cancer with rising PSA after local therapy: EMBARK study design. BMJ Open. 2021 Aug 12;11(8):e046588. doi: 10.1136/bmjopen-2020-046588.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT02319837
• Other Study ID Numbers: MDV3100-13; C3431004 ( Other Identifier: Alias Study Number ); 2014-001634-28 ( EudraCT Number )
• First Posted: December 18, 2014
• Results First Posted: March 25, 2024
• Last Update Posted: March 25, 2024
• Last Verified: March 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Leuprolide; Fertility Agents, Female; Fertility Agents; Reproductive Control Agents; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents