Study of Enzalutamide (Formerly MDV3100) as a Neoadjuvant Therapy for Patients Undergoing Prostatectomy for Localized Prostate Cancer

This study has been completed.
Sponsor:
Collaborator:
Astellas Pharma Inc
Information provided by (Responsible Party):
Medivation, Inc.
ClinicalTrials.gov Identifier:
NCT01547299
First received: February 27, 2012
Last updated: April 21, 2015
Last verified: April 2015
  Purpose

The purpose of this study is to determine if enzalutamide is an effective therapy in treating localized prostate cancer prior to prostatectomy.


Condition Intervention Phase
Prostate Cancer
Drug: Enzalutamide
Drug: Leuprolide
Drug: Dutasteride
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open-Label, Phase 2 Study of MDV3100 as a Neoadjuvant Therapy for Patients Undergoing Prostatectomy for Localized Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Medivation, Inc.:

Primary Outcome Measures:
  • Pathologic Complete Response Rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Pathologic complete response rate following triplet therapy (enzalutamide in combination with leuprolide and dutasteride) and enzalutamide alone when administered as neoadjuvant therapy for 6 months prior to prostatectomy in patients with localized prostate cancer. Pathologic complete response is defined as the absence of morphologically identifiable carcinoma in the prostatectomy specimen, as evaluated by the site pathologist using standard methods.


Secondary Outcome Measures:
  • Percentage of Patients With Positive Surgical Margins [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To determine the percentage of patients with positive surgical margins at prostatectomy as assessed by the local and central pathologist.

  • Percentage of Patients With Extracapsular Extension: Local Review [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To determine the percentage of patients with extracapsular extension at prostatectomy as assessed by the local pathologist.

  • Percentage of Patients With Extracapsular Extension: Central Review [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To determine the percentage of patients with extracapsular extension at prostatectomy as assessed by the central pathologist.

  • Percentage of Patients With Positive Seminal Vesicles [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To determine the percentage of patients with positive seminal vesicles at prostatectomy as assessed by the local and central pathologist.

  • Percentage of Patients With Positive Lymph Nodes [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To determine the percentage of patients with positive lymph nodes at prostatectomy as assessed by the local and central pathologist.

  • Prostate-Specific Antigen (PSA) Nadir [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To determine the effects on PSA as measured by the lowest postbaseline PSA value prior to prostatectomy.

  • Time to Prostate-Specific Antigen (PSA) Nadir [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To determine the effects on PSA as measured by the time to the lowest postbaseline PSA value prior to prostatectomy.

  • Percentage of Patients With Reduction in Prostate-Specific Antigen (PSA) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To determine the effects on PSA as measured by the percentage of patients with PSA < 0.2 ng/mL, and a 50% and 90% decrease in PSA value prior to prostatectomy.

  • Health-Related Quality of Life (HRQoL): The Expanded Prostate Cancer Index Composite (EPIC) Sexual Domain Summary Score [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    EPIC Sexual Domain is an HRQoL instrument that measures the effects of prostate cancer treatment on a patient's sexual function and sexual satisfaction. Best change from baseline category in EPIC sexual domain summary score is summarized below. Categories are worsened (decrease of at least 1 minimally important difference), stable (changed by less than 1 minimally important difference), or improved (increase of at least 1 minimally important difference). Minimally important difference is defined as one-half the standard deviation of the score of interest at baseline.

  • Health-Related Quality of Life (HRQoL): The Expanded Prostate Cancer Index Composite (EPIC) Sexual Function Subscale Score [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    EPIC Sexual Domain is an HRQoL instrument that measures the effects of prostate cancer treatment on a patient's sexual function and sexual satisfaction. Best change from baseline category in EPIC sexual function subscale score is summarized below. Categories are worsened (decrease of at least 1 minimally important difference), stable (changed by less than 1 minimally important difference), or improved (increase of at least 1 minimally important difference). Minimally important difference is defined as one-half the standard deviation of the score of interest at baseline.

  • Health-Related Quality of Life (HRQoL): The Expanded Prostate Cancer Index Composite (EPIC) Sexual Bother Subscale Score [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    EPIC Sexual Domain is an HRQoL instrument that measures the effects of prostate cancer treatment on a patient's sexual function and sexual satisfaction. Best change from baseline category in EPIC sexual bother subscale score is summarized below. Categories are worsened (decrease of at least 1 minimally important difference), stable (changed by less than 1 minimally important difference), or improved (increase of at least 1 minimally important difference). Minimally important difference is defined as one-half the standard deviation of the score of interest at baseline.

  • Health-Related Quality of Life (HRQoL): The Expanded Prostate Cancer Index Composite (EPIC) Hormonal Domain Summary Score [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    EPIC Hormonal Domain is an HRQoL instrument that measures the effects of prostate cancer treatment on a patient's hormonal function. Best change from baseline category in EPIC hormonal domain summary score is summarized below. Categories are worsened (decrease of at least 1 minimally important difference), stable (changed by less than 1 minimally important difference), or improved (increase of at least 1 minimally important difference). Minimally important difference is defined as one-half the standard deviation of the score of interest at baseline.

  • Health-Related Quality of Life (HRQoL): The Expanded Prostate Cancer Index Composite (EPIC) Hormonal Function Subscale Score [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    EPIC Hormonal Domain is an HRQoL instrument that measures the effects of prostate cancer treatment on a patient's hormonal function. Best change from baseline category in EPIC hormonal function subscale score is summarized below. Categories are worsened (decrease of at least 1 minimally important difference), stable (changed by less than 1 minimally important difference), or improved (increase of at least 1 minimally important difference). Minimally important difference is defined as one-half the standard deviation of the score of interest at baseline.

  • Health-Related Quality of Life (HRQoL): The Expanded Prostate Cancer Index Composite (EPIC) Hormonal Bother Subscale Score [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    EPIC Hormonal Domain is an HRQoL instrument that measures the effects of prostate cancer treatment on a patient's hormonal function. Best change from baseline category in EPIC hormonal bother subscale score is summarized below. Categories are worsened (decrease of at least 1 minimally important difference), stable (changed by less than 1 minimally important difference), or improved (increase of at least 1 minimally important difference). Minimally important difference is defined as one-half the standard deviation of the score of interest at baseline.

  • Health-Related Quality of Life (HRQoL): The Twelve-Item Short Form Version 2 General Health Domain Score [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    The Twelve-Item Short Form Version 2 is an HRQoL instrument that measures general health and well-being across physical and mental components. Best change from baseline category in general health domain score is summarized below. Categories are worsened (decrease of at least 1 minimally important difference), stable (changed by less than 1 minimally important difference), or improved (increase of at least 1 minimally important difference). Minimally important difference is defined as one-half the standard deviation of the score of interest at baseline.

  • Health-Related Quality of Life (HRQoL): The Twelve-Item Short Form Version 2 Physical Functioning Domain Score [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    The Twelve-Item Short Form Version 2 is an HRQoL instrument that measures general health and well-being across physical and mental components. Best change from baseline category in physical functioning domain score is summarized below. Categories are worsened (decrease of at least 1 minimally important difference), stable (changed by less than 1 minimally important difference), or improved (increase of at least 1 minimally important difference). Minimally important difference is defined as one-half the standard deviation of the score of interest at baseline.

  • Health-Related Quality of Life (HRQoL): The Twelve-Item Short Form Version 2 Role-Emotional Domain Score [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    The Twelve-Item Short Form Version 2 is an HRQoL instrument that measures general health and well-being across physical and mental components. Best change from baseline category in role-emotional domain score is summarized below. Categories are worsened (decrease of at least 1 minimally important difference), stable (changed by less than 1 minimally important difference), or improved (increase of at least 1 minimally important difference). Minimally important difference is defined as one-half the standard deviation of the score of interest at baseline.

  • Health-Related Quality of Life (HRQoL): The Twelve-Item Short Form Version 2 Mental Component Summary [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    The Twelve-Item Short Form Version 2 is an HRQoL instrument that measures general health and well-being across physical and mental components. Best change from baseline category in mental component summary is summarized below. Categories are worsened (decrease of at least 1 minimally important difference), stable (changed by less than 1 minimally important difference), or improved (increase of at least 1 minimally important difference). Minimally important difference is defined as one-half the standard deviation of the score of interest at baseline.

  • Pharmacodynamic Effects: Tissue Dihydrotestosterone (DHT) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To determine pharmacodynamic effects as measured by tissue DHT in prostatectomy specimens following radical prostatectomy.

  • Pharmacodynamic Effects: Tissue Testosterone [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To determine pharmacodynamic effects as measured by tissue testosterone in prostatectomy specimens following radical prostatectomy.

  • Pharmacodynamic Effects: Assessment of Apoptosis [ Time Frame: 6 months ] [ Designated as safety issue: No ]

    To determine the effects of triplet therapy and enzalutamide alone on apoptosis in prostatectomy specimens.

    Assessment of apoptosis was not performed due to limited amounts of tissue available.


  • Pharmacodynamic Effects: Assessment of Mitotic Index [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To determine the effects of triplet therapy and enzalutamide alone on mitotic index (rate of cell growth) in prostatectomy specimens.

  • Pharmacodynamic Effects: Assessment of Androgen Receptor Signaling [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To determine the effects of triplet therapy and enzalutamide alone on androgen receptor signaling in prostatectomy specimens.

  • Serum Dihydrotestosterone (DHT): Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Serum Dihydrotestosterone (DHT): 6 Months Postbaseline [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Change From Baseline in Serum Dihydrotestosterone (DHT) [ Time Frame: Baseline, 6 months ] [ Designated as safety issue: No ]
    To determine serum hormone effects as measured by change in DHT values from baseline to the completion of therapy.

  • Serum Testosterone: Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Serum Testosterone: 6 Months Postbaseline [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Change From Baseline in Serum Testosterone [ Time Frame: Baseline, 6 months ] [ Designated as safety issue: No ]
    To determine serum hormone effects as measured by change in testosterone at baseline and at completion of therapy.

  • Number of Patients With Adverse Events (AEs) That Led to Dose Interruption, Dose Reduction, and Study Drug Discontinuation [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    To assess the number of patients with AEs that led to permanent discontinuation of enzalutamide, temporary interruption of enzalutamide, dose reduction of enzalutamide, or study drug (enzalutamide, leuprolide, or dutasteride) discontinuation.


Enrollment: 52
Study Start Date: March 2012
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Enzalutamide alone
Enzalutamide 160 mg, orally, once daily
Drug: Enzalutamide
Other Name: MDV3100
Experimental: Enzalutamide & Leuprolide & Dutasteride
Enzalutamide 160 mg, orally, once daily and leuprolide 22.5 mg, intramuscular injection, every 3 months, and dutasteride, 0.5 mg, orally, once daily
Drug: Enzalutamide
Other Name: MDV3100
Drug: Leuprolide Drug: Dutasteride

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Willing to provide informed consent
  • 18 years of age or older
  • Histologically confirmed adenocarcinoma of the prostate
  • Must be a candidate for radical prostatectomy and considered surgically resectable

Exclusion Criteria:

  • Stage T4 prostate cancer by clinical or radiologic evaluation
  • Treatment with an investigational agent within 4 weeks prior to randomization
  • Received therapy for other neoplastic disorders within 5 years
  • Hypogonadism or severe androgen deficiency
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01547299

Locations
United States, Massachusetts
Boston, Massachusetts, United States, 02215
United States, Washington
Seattle, Washington, United States, 98195
Canada, British Columbia
Vancouver, British Columbia, Canada, V5Z 1M9
Canada, Ontario
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
Medivation, Inc.
Astellas Pharma Inc
  More Information

No publications provided

Responsible Party: Medivation, Inc.
ClinicalTrials.gov Identifier: NCT01547299     History of Changes
Other Study ID Numbers: MDV3100-07
Study First Received: February 27, 2012
Results First Received: March 30, 2015
Last Updated: April 21, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Medivation, Inc.:
prostate cancer
prostatectomy
neoadjuvant

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Prostatic Diseases
Urogenital Neoplasms
Dutasteride
Leuprolide
5-alpha Reductase Inhibitors
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Enzyme Inhibitors
Fertility Agents
Fertility Agents, Female
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses
Urological Agents

ClinicalTrials.gov processed this record on August 03, 2015