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

Pfizer

Status and phase: Active, not recruiting; Phase 3

Conditions: Hormone Sensitive Prostate Cancer; Prostate Cancer; Cancer of the Prostate

Treatments: Drug: Enzalutamide; Drug: Leuprolide Open Label; Drug: Placebo (No longer applicable in Open Label study period)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02319837

MDV3100-13

C3431004 (Other Identifier)

2014-001634-28 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 1,068 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,068 participants in 3 patient groups

Enzalutamide plus leuprolide

Experimental group

Description:

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

Treatment:

Drug: Leuprolide Open Label

Drug: Enzalutamide

Enzalutamide monotherapy

Experimental group

Description:

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

Treatment:

Drug: Enzalutamide

Leuprolide plus placebo

Active Comparator group

Description:

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.

Treatment:

Drug: Placebo (No longer applicable in Open Label study period)