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

NCT02677896

Last updated date
Study Location
Site US10016
Homewood, Alabama, 35209, United States
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Metastatic Hormone Sensitive Prostate Cancer
Sex
Male
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- 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 (for bone disease) or metastatic lesions on computed tomography (CT) or magnetic resonance imaging (MRI) scan (for soft tissue). 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.

Inclusion Criteria for Open-Label Extension:

- Subject received randomized double-blind treatment in ARCHES

- Subject has not met any of the discontinuation criteria in the main ARCHES protocol

- Subject is willing to maintain ADT with LHRH agonist or antagonist or has had a bilateral orchiectomy.

- Subject is able to swallow enzalutamide capsules whole and to comply with study requirements throughout the study

- Subject and subject's female partner agree to follow contraception and sperm donation requirements in main protocol

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- 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, intended for the
treatment of prostate cancer.


- 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


Exclusion Criteria for Open-Label Extension:


- Subject has taken commercially available enzalutamide (Xtandi).


- Subject's disease has progressed radiographically during the double-blind period of
the study and treatment with study drug was stopped prior to study-wide unblinding.
(Note: Subjects who progressed radiographically while in the double-blind portion of
the study and continued treatment per protocol are allowed to participate in the open
label extension.)


- After study-wide unblinding, subject has started any new investigational agent or
anti-neoplastic therapy intended to treat prostate cancer


- Subject has any clinically significant disorder or condition including excessive
alcohol or drug abuse, or secondary malignancy, which may interfere with study
participation


- Subject has current or previously treated brain metastasis or active leptomeningeal
disease


- Subject has a history of seizure or any condition that may increase the risk of
seizure

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Metastatic Hormone Sensitive Prostate CancerA Study of Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC)
NCT02677896
  1. Homewood, Alabama
  2. Anchorage, Alaska
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  77. Seinäjoki, Länsi-Suomen Lääni
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  120. Chuo-ku, Osaka
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  123. Koto-ku, Tokyo
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  203. Withington, Manchester
Male
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE A Study of Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC)
Official Title  ICMJE 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 Summary The purpose of this study was 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 also evaluated the safety of enzalutamide plus ADT in mHSPC.
Detailed Description Following unblinding at the end of the double-blind period and demonstration of a statistically significant advantage of enzalutamide over placebo when added to ADT as assessed by the primary endpoint of rPFS, subjects were eligible to transition to an open-label portion of the study.
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 Metastatic Hormone Sensitive Prostate Cancer
Intervention  ICMJE
  • Drug: Enzalutamide
    Oral
    Other Name: Xtandi
  • Drug: Placebo
    Oral
Study Arms  ICMJE
  • Experimental: Enzalutamide + Androgen Deprivation Therapy (ADT)
    Participants received enzalutamide orally once daily. ADT (either bilateral orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonist/antagonist) was maintained during study treatment as per standard of care and provided by the site's pharmacy stock.
    Intervention: Drug: Enzalutamide
  • Placebo Comparator: Placebo + Androgen Deprivation Therapy (ADT)
    Participants received matching placebo orally once daily. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment as per standard of care and provided by the site's pharmacy stock.
    Intervention: Drug: Placebo
Publications * Armstrong AJ, Szmulewitz RZ, Petrylak DP, Holzbeierlein J, Villers A, Azad A, Alcaraz A, Alekseev B, Iguchi T, Shore ND, Rosbrook B, Sugg J, Baron B, Chen L, Stenzl A. ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy With Enzalutamide or Placebo in Men With Metastatic Hormone-Sensitive Prostate Cancer. J Clin Oncol. 2019 Nov 10;37(32):2974-2986. doi: 10.1200/JCO.19.00799. Epub 2019 Jul 22.

*   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: January 26, 2018)
1150
Original Estimated Enrollment  ICMJE
 (submitted: February 5, 2016)
1100
Estimated Study Completion Date  ICMJE May 2021
Actual Primary Completion Date October 14, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 (for bone disease) or metastatic lesions on computed tomography (CT) or magnetic resonance imaging (MRI) scan (for soft tissue). 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.

Inclusion Criteria for Open-Label Extension:

  • Subject received randomized double-blind treatment in ARCHES
  • Subject has not met any of the discontinuation criteria in the main ARCHES protocol
  • Subject is willing to maintain ADT with LHRH agonist or antagonist or has had a bilateral orchiectomy.
  • Subject is able to swallow enzalutamide capsules whole and to comply with study requirements throughout the study
  • Subject and subject's female partner agree to follow contraception and sperm donation requirements in main protocol

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-? 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, intended for the treatment of prostate cancer.
  • 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/?L, platelet count < 100000/?L 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 ?mol/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

Exclusion Criteria for Open-Label Extension:

  • Subject has taken commercially available enzalutamide (Xtandi).
  • Subject's disease has progressed radiographically during the double-blind period of the study and treatment with study drug was stopped prior to study-wide unblinding. (Note: Subjects who progressed radiographically while in the double-blind portion of the study and continued treatment per protocol are allowed to participate in the open label extension.)
  • After study-wide unblinding, subject has started any new investigational agent or anti-neoplastic therapy intended to treat prostate cancer
  • Subject has any clinically significant disorder or condition including excessive alcohol or drug abuse, or secondary malignancy, which may interfere with study participation
  • Subject has current or previously treated brain metastasis or active leptomeningeal disease
  • Subject has a history of seizure or any condition that may increase the risk of seizure
Sex/Gender  ICMJE
Sexes Eligible for Study:Male
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 Argentina,   Australia,   Belgium,   Canada,   Chile,   Denmark,   Finland,   France,   Germany,   Israel,   Italy,   Japan,   Korea, Republic of,   Netherlands,   New Zealand,   Poland,   Romania,   Russian Federation,   Slovakia,   Spain,   Sweden,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02677896
Other Study ID Numbers  ICMJE 9785-CL-0335
2015-003869-28 ( 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:Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
Supporting Materials:Study Protocol
Supporting Materials:Statistical Analysis Plan (SAP)
Supporting Materials:Clinical Study Report (CSR)
Time Frame:Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
Access Criteria:Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
URL:https://www.clinicalstudydatarequest.com/
Responsible Party Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
Study Sponsor  ICMJE Astellas Pharma Global Development, Inc.
Collaborators  ICMJE Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
Investigators  ICMJE
Study Director:Medical DirectorAstellas Pharma Global Development, Inc.
PRS Account Astellas Pharma Inc
Verification Date July 2020

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