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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02319837
Recruitment Status : Active, not recruiting
First Posted : December 18, 2014
Last Update Posted : July 31, 2019
Sponsor:
Collaborators:
Astellas Pharma Inc
Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE December 14, 2014
First Posted Date  ICMJE December 18, 2014
Last Update Posted Date July 31, 2019
Actual Study Start Date  ICMJE December 17, 2014
Estimated Primary Completion Date July 7, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 13, 2018)
Metastasis-free survival (MFS) [ Time Frame: Up to approximatey 67 months ]
Compared between enzalutamide plus leuprolide and placebo plus leuprolide.
Original Primary Outcome Measures  ICMJE
 (submitted: December 17, 2014)
Metastasis-free survival (MFS) [ Time Frame: During Study Period up to 56 months ]
Change History Complete list of historical versions of study NCT02319837 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 13, 2018)
  • Overall survival [ Time Frame: Up to approximately 96 months ]
  • Time to castration resistance [ Time Frame: Up to approximately 67 months ]
  • Composite of safety [ Time Frame: Up to approximately 67 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.
  • Metastasis-free survival (MFS) [ Time Frame: Up to approximately 67 months ]
    Compared between enzalutamide monotherapy versus placebo plus leuprolide.
  • Time to prostate specific antigen (PSA) progression; [ Time Frame: Up to approximately 67 months ]
  • Time to first use of new antineoplastic therapy [ Time Frame: Up to approximately 67 months ]
  • Time to distant metastasis [ Time Frame: Up to approximately 67 months ]
  • Proportion of patients per group who remain treatment free 2 years after suspension of study drug treatment at week 37 due to undetectable PSA [ Time Frame: From baseline (week 37) up to 67 months ]
  • Proportion of patients per group with undetectable PSA 2 years after suspension of study drug treatment at week 37 due to undetectable PSA [ Time Frame: From baseline (week 37) up to 67 months ]
  • Proportion of patients per group with undetectable PSA at 36 weeks on study drug [ Time Frame: At week 36 ]
  • Time to resumption of any hormonal therapy following suspension at week 37 due to undetectable PSA [ Time Frame: From baseline (week 37) up to 67 months ]
  • Time to symptomatic progression [ Time Frame: Up to approximately 67 months ]
  • Time to first symptomatic skeletal event [ Time Frame: Up to approximately 96 months ]
  • Time to clinically relevant pain [ Time Frame: Up to approximately 67 months ]
  • Quality of life via the Functional Assessment of Cancer Therapy Prostate (FACT P) questionnaire, [ Time Frame: Up to approximately 67 months ]
  • Quality of life via the European Quality of Life 5 Dimensions 5 Levels Health Questionnaire (EQ 5D 5L), [ Time Frame: Up to approximately 67 months ]
  • Quality of life via the Quality of Life Questionnaire Prostate 25 (QLQ PR25) module [ Time Frame: Up to approximately 67 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 17, 2014)
  • 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 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 (2 ng/mL) 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 measure of incidence and severity of adverse events, serious adverse events, [ Time Frame: During Study Period up to 56 months ]
    incidence of permanent treatment discontinuation due to adverse events, and incidence of new clinically significant changes in clinical laboratory values and vital signs.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Study of Enzalutamide Plus Leuprolide in Patients With Nonmetastatic Prostate Cancer (EMBARK)
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Hormone Sensitive Prostate Cancer
  • Prostate Cancer
  • Cancer of the Prostate
Intervention  ICMJE
  • Drug: Enzalutamide
    Other Names:
    • MDV3100
    • Xtandi
  • Drug: Placebo
    Sugar pill to mimic enzalutamide
  • Drug: Leuprolide
    Other Names:
    • Eligard
    • Leuprolide Acetate
    • Leuprorelin
    • Lupron
Study Arms  ICMJE
  • 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
    Interventions:
    • Drug: Enzalutamide
    • Drug: Leuprolide
  • Experimental: Enzalutamide monotherapy
    Enzalutamide (160 mg) administered as four 40-mg capsules by mouth once daily
    Intervention: Drug: Enzalutamide
  • 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
    Interventions:
    • Drug: Placebo
    • Drug: Leuprolide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 29, 2019)
1068
Original Estimated Enrollment  ICMJE
 (submitted: December 17, 2014)
1860
Estimated Study Completion Date  ICMJE July 31, 2023
Estimated Primary Completion Date July 7, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Gender Based Eligibility: Yes
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Brazil,   Canada,   Denmark,   Finland,   France,   Italy,   Korea, Republic of,   Netherlands,   Poland,   Slovakia,   Spain,   Sweden,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02319837
Other Study ID Numbers  ICMJE MDV3100-13
C3431004 ( Other Identifier: Alias Study Number )
2014-001634-28 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
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
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE
  • Astellas Pharma Inc
  • Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
Investigators  ICMJE
Study Director: Pfizer Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP