We updated the design of this site on September 25th. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

This study is currently recruiting participants.
Verified August 2017 by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
Sponsor:
ClinicalTrials.gov Identifier:
NCT02677896
First Posted: February 9, 2016
Last Update Posted: August 17, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Medivation, Inc.
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
  Purpose
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.

Condition Intervention Phase
Metastatic Hormone Sensitive Prostate Cancer Drug: Enzalutamide Drug: Placebo Phase 3

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

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):

Primary Outcome Measures:
  • Radiographic progression-free survival (rPFS) [ Time Frame: Up to 4 years ]
    Defined as the time from randomization to the first objective evidence of radiographic disease progression as assessed by central review or death (defined as death from any cause within 24 weeks from study drug discontinuation), whichever comes first.


Secondary Outcome Measures:
  • Overall survival (OS) [ Time Frame: Up to 7 years ]
    Defined as the time from randomization to death from any cause.

  • Time to first symptomatic skeletal event (SSE) [ Time Frame: Up to 4 years ]
    Defined as the time from randomization to the occurrence of the first SSE. SSE is defined as radiation or surgery to bone, clinically apparent pathological bone fracture or spinal cord compression.

  • Time to castration resistance [ Time Frame: Up to 4 years ]
    Defined as the time from randomization to the first castration-resistant event (radiographic disease progression, prostate-specific antigen (PSA) progression or SSE), whichever occurs first.

  • Time to deterioration of quality of life (QoL) [ Time Frame: Up to 4 years ]
    Defined as time from randomization to a 10-point reduction of the Functional Assessment of Cancer Therapy - Prostate (FACT-P) total score

  • Time to initiation of a new antineoplastic therapy [ Time Frame: Up to 4 years ]
    Defined as time from randomization to the initiation of antineoplastic subsequent to the study treatments.

  • Time to PSA progression [ Time Frame: Up to 4 years ]
    PSA progression is defined as a ≥ 2 µg/L (2 ng/mL) above the nadir.

  • PSA undetectable rate [ Time Frame: Up to 4 years ]
    Defined as percentage of subjects with detectable (< 0.2 ng/mL) during study treatment.

  • Objective response rate [ Time Frame: Up to 4 years ]
    Defined as the percentage of subjects with measureable disease at baseline who achieved a complete or partial response in their soft tissue disease using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria.

  • Time to pain progression [ Time Frame: Up to 4 years ]
    Defined as time from randomization to an increase of 30% in pain severity score from baseline using the Brief Pain Inventory-Short Form (BPI-SF)


Estimated Enrollment: 1100
Actual Study Start Date: March 7, 2016
Estimated Study Completion Date: December 2023
Estimated Primary Completion Date: April 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Enzalutamide plus androgen deprivation therapy (ADT)
Subjects will receive enzalutamide once daily. ADT (either bilateral orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonist/antagonist) will be maintained during study treatment as per standard of care (SOC) and provided by the site's pharmacy stock.
Drug: Enzalutamide
Oral
Other Name: Xtandi
Placebo Comparator: Placebo plus androgen deprivation therapy (ADT)
Subjects will receive matching placebo once daily. ADT (either bilateral orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonist/antagonist) will be maintained during study treatment as per standard of care (SOC) and provided by the site's pharmacy stock.
Drug: Placebo
Oral

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


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

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02677896


Contacts
Contact: Astellas Pharma Global Development 800-888-7704 ext 5473 astellas.registration@astellas.com

  Show 232 Study Locations
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Medivation, Inc.
Investigators
Study Director: Medical Director Astellas Pharma Global Development, Inc.
  More Information

Responsible Party: Astellas Pharma Global Development, Inc.
ClinicalTrials.gov Identifier: NCT02677896     History of Changes
Other Study ID Numbers: 9785-CL-0335
2015-003869-28 ( EudraCT Number )
First Submitted: February 5, 2016
First Posted: February 9, 2016
Last Update Posted: August 17, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):
Androgen Deprivation Therapy (ADT)
Metastatic hormone sensitive prostate cancer
Xtandi
Enzalutamide

Additional relevant MeSH terms:
Prostatic Neoplasms
Hypersensitivity
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Immune System Diseases
Hormones
Estrogens, Conjugated (USP)
Methyltestosterone
Prolactin Release-Inhibiting Factors
Androgens
Ascorbic Acid
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Vitamins
Micronutrients
Growth Substances
Estrogens
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anabolic Agents