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

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: September 15, 2023

Interventions

  • Drug: Enzalutamide
  • Drug: Placebo
    • Sugar pill to mimic enzalutamide
  • Drug: Leuprolide

Arms, Groups and Cohorts

  • 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

Clinical Trial Outcome Measures

Primary Measures

  • Metastasis-free survival (MFS)
    • Time Frame: Up to approximatey 67 months
    • Compared between enzalutamide plus leuprolide and placebo plus leuprolide.

Secondary Measures

  • 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

Participating in This Clinical Trial

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

Gender Eligibility: Male

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Pfizer
  • Collaborator
    • Astellas Pharma Inc
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Pfizer Pfizer CT.gov Call Center, Study Director, Pfizer

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