A Study of Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC)

Study ID
STU 042016-056

Study Sites

  • Zale Lipshy University Hospital

Contact
Dendra Von Merveldt
214/645-8789
DENDRA.VONMERVELDT@UTSouthwestern.edu

Principal Investigator
Kevin Courtney, M.D., Ph.D.

Official Title

A Multinational, Phase 3, Randomized, Double-blind, Placebo-controlled Efficacy and Safety Study of Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC)

Brief Overview

The purpose of this study is to evaluate the efficacy of enzalutamide plus androgen deprivation therapy (ADT) as measured by radiographic progression-free survival (rPFS) based on central review. The study will also evaluate the safety of enzalutamide plus ADT in mHSPC.

Eligibility

Inclusion Criteria:
- Subject is considered an adult according to local regulation at the time of signing informed consent.
- Subject is diagnosed with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation, signet cell or small cell histology.
- Subject has metastatic prostate cancer documented by positive bone scan or metastatic lesions on computed tomography (CT) or magnetic resonance imaging (MRI) scan. Subjects whose disease spread is limited to regional pelvic lymph nodes are not eligible.
- Once randomized at day 1, subject must maintain ADT with an LHRH agonist or antagonist during study treatment or have a history of bilateral orchiectomy (i.e., medical or surgical castration).
- Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Exclusion Criteria:
- Subject has received any prior pharmacotherapy, radiation therapy or surgery for metastatic prostate cancer (the following exceptions are permitted):
- Up to 3 months of ADT with LHRH agonists or antagonists or orchiectomy with or without concurrent antiandrogens prior to day 1, with no radiographic evidence of disease progression or rising PSA levels prior to day 1;
- Subject may have 1 course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease if it was administered at least 4 weeks prior to day 1;
- Up to 6 cycles of docetaxel therapy with final treatment administration completed within 2 months of day 1 and no evidence of disease progression during or after the completion of docetaxel therapy;
- Up to 6 months of ADT with LHRH agonists or antagonists or orchiectomy with or without concurrent antiandrogens prior to day 1 if subject was treated with docetaxel, with no radiographic evidence of disease progression or rising PSA levels prior to day 1;
- Prior ADT given for < 39 months in duration and > 9 months before randomization as neoadjuvant/adjuvant therapy.
- Subject had a major surgery within 4 weeks prior to day 1.
- Subject received treatment with 5-α reductase inhibitors (finasteride, dutasteride) within 4 weeks prior to day 1.
- Subject received treatment with estrogens, cyprotoerone acetate or androgens within 4 weeks prior to day 1.
- Subject received treatment with systemic glucocorticoids greater than the equivalent of 10 mg per day of prednisone within 4 weeks prior to day 1.
- Subject received treatment with herbal medications that have known hormonal antiprostate cancer activity and/or are known to decrease PSA levels within 4 weeks prior to day 1.
- Subject received prior aminoglutethimide, ketoconazole, abiraterone acetate or enzalutamide for the treatment of prostate cancer or participation in a clinical study of an investigational agent that inhibits the AR or androgen synthesis (e.g., TAK-700, ARN-509, ODM-201).
- Subject has known or suspected brain metastasis or active leptomeningeal disease.
- Subject has absolute neutrophil count < 1500/μL, platelet count < 100000/μL or hemoglobin < 10 g/dL (6.2 mmol/L).
- Subject has total bilirubin (TBL) ≥ 1.5 x the upper limit of normal (ULN) (except subjects with documented Gilbert's disease), or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2.5 x the ULN .
- Subject has creatinine > 2 mg/dL (177 μmol/L).
- Subject has albumin < 3.0 g/dL (30 g/L).
- Subject has a history of seizure or any condition that may predispose to seizure.
- Subject has history of loss of consciousness or transient ischemic attack within 12 months prior to day 1.
- Subject has clinically significant cardiovascular disease.
- Subject received bisphosphonates or denosumab within 2 weeks prior to day 1 unless administered at stable dose or to treat diagnosed osteoporosis