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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2017 by Medivation, Inc.
Astellas Pharma Inc
Information provided by (Responsible Party):
Medivation, Inc. Identifier:
First received: December 14, 2014
Last updated: April 7, 2017
Last verified: March 2017
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.

Condition Intervention Phase
Hormone Sensitive Prostate Cancer
Prostate Cancer
Cancer of the Prostate
Drug: Enzalutamide
Drug: Placebo
Drug: Leuprolide
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
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

Resource links provided by NLM:

Further study details as provided by Medivation, Inc.:

Primary Outcome Measures:
  • Metastasis-free survival (MFS) [ Time Frame: During Study Period up to 56 months ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: During Study Period up to 110 months ]
  • Proportion of patients per group who remain treatment-free 2 years after suspension of study drug treatment at week 37 due to undetectable Prostate-Specific Antigen (PSA). [ Time Frame: During Study Period up to 56 months ]
  • Time to castration resistance [ Time Frame: During Study Period up to 56 months ]
    The time to castration resistance is defined as the time from randomization to the date of the first PSA increase while on study drug treatment that is >= 25% and >= 2 μg/L above the nadir or screening value, whichever is lower, and that is confirmed by a second consecutive value obtained at least 3 weeks later.

  • Prostate cancer-specific survival [ Time Frame: During Study Period up to 110 months ]
  • Time to first symptomatic skeletal event [ Time Frame: During Study Period up to 56 months ]
  • Composite of safety [ Time Frame: During Study Period up to 56 months ]
    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.

Estimated Enrollment: 1860
Study Start Date: December 2014
Estimated Study Completion Date: December 2020
Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: Enzalutamide
Other Names:
  • MDV3100
  • Xtandi
Drug: Leuprolide
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: 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
Drug: Placebo
Sugar pill to mimic enzalutamide
Drug: Leuprolide
Other Names:
  • Eligard
  • Leuprolide Acetate
  • Leuprorelin
  • Lupron


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT02319837

Contact: Medivation Clinical Operations +1 (415) 543-3470
Contact: Medivation Clinical Trial Disclosure

  Show 177 Study Locations
Sponsors and Collaborators
Medivation, Inc.
Astellas Pharma Inc
Study Director: Medical Director Medivation, Inc.
  More Information

Responsible Party: Medivation, Inc. Identifier: NCT02319837     History of Changes
Other Study ID Numbers: MDV3100-13
Study First Received: December 14, 2014
Last Updated: April 7, 2017

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents processed this record on April 27, 2017