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: March 30, 2015
Last verified: March 2015

February 27, 2012
March 30, 2015
March 2012
November 2013   (final data collection date for primary outcome measure)
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.
Pathological Complete Response Rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
To assess the pathological complete response rate following triplet therapy (MDV3100 in combination with leuprolide and dutasteride) and MDV3100 alone when administered as neoadjuvant therapy for 6 months prior to prostatectomy in patients with localized prostate cancer
Complete list of historical versions of study NCT01547299 on ClinicalTrials.gov Archive Site
  • 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: The Expanded Prostate Cancer Index Composite (EPIC) Sexual Domain Summary Score [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Best change from baseline category in EPIC sexual domain summary score. 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: The Expanded Prostate Cancer Index Composite (EPIC) Sexual Function Subscale Score [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Best change from baseline category in EPIC sexual function subscale score. 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: The Expanded Prostate Cancer Index Composite (EPIC) Sexual Bother Subscale Score [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Best change from baseline category in EPIC sexual bother subscale score. 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: The Expanded Prostate Cancer Index Composite (EPIC) Hormonal Domain Summary Score [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Best change from baseline category in EPIC hormonal domain summary score. 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: The Expanded Prostate Cancer Index Composite (EPIC) Hormonal Function Subscale Score [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Best change from baseline category in EPIC hormonal function subscale score. 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: The Expanded Prostate Cancer Index Composite (EPIC) Hormonal Bother Subscale Score [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Best change from baseline category in EPIC hormonal bother subscale score. 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: The Twelve-Item Short Form Version 2 General Health Domain Score [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Best change from baseline category in general health domain score. 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: The Twelve-Item Short Form Version 2 Physical Functioning Domain Score [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Best change from baseline category in physical functioning domain score. 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: The Twelve-Item Short Form Version 2 Role Emotional Domain Score [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Best change from baseline category in role emotional domain score. 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: The Twelve-Item Short Form Version 2 Mental Component Summary [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Best change from baseline category in mental component summary. 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.
  • Safety and Tolerability: Adverse Events (AEs) Leading to Dose Interruption, Dose Reduction, and Study Drug Discontinuation [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    To assess the safety and tolerability of triplet therapy and enzalutamide alone in the neoadjuvant setting by assessment of adverse events leading to permanent discontinuation of enzalutamide, temporary interruption of enzalutamide, dose reduction of enzalutamide, or study drug (enzalutamide, leuprolide, or dutasteride) discontinuation.
  • PSA [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
    To determine the effects on prostate-specific antigen (PSA) (including median nadir value, percentage of patients achieving PSA < 0.2 ng/mL, the proportion of patients achieving 50% and 90% decrease in PSA, and time to PSA nadir) for triplet therapy and MDV3100 alone
  • Determine the rate of positive surgical margins [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To determine the rate of positive surgical margins, extracapsular extension, positive seminal vesicles and lymph nodes at the time of prostatectomy for triplet therapy and MDV3100 alone.
  • Pharmacodynamics [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To determine the effects of triplet therapy and MDV3100 alone on selected pharmacodynamic markers on prostatectomy specimens including apoptosis, mitotic index, androgen receptor signaling, and others.
  • Determine effects on testosterone and dihydrotestosterone (DHT) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To determine the effects on testosterone and dihydrotestosterone (DHT) (including median values of testosterone and DHT during and at completion of therapy) for triplet therapy and MDV3100 alone
  • Assess the safety and tolerability of triplet therapy and MDV3100 alone [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    To assess the safety and tolerability of triplet therapy and MDV3100 alone in the neoadjuvant setting. Safety and tolerability will be documented throughout the study by assessment of adverse events, vital signs, electrocardiograms (ECGs), and laboratory assessments
Not Provided
Not Provided
 
Study of Enzalutamide (Formerly MDV3100) as a Neoadjuvant Therapy for Patients Undergoing Prostatectomy for Localized Prostate Cancer
A Randomized, Open-Label, Phase 2 Study of MDV3100 as a Neoadjuvant Therapy for Patients Undergoing Prostatectomy for Localized Prostate Cancer

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

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Prostate Cancer
  • Drug: Enzalutamide
    Other Name: MDV3100
  • Drug: Leuprolide
  • Drug: Dutasteride
  • Experimental: Enzalutamide alone
    Enzalutamide 160 mg, orally, once daily
    Intervention: Drug: Enzalutamide
  • 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
    Interventions:
    • Drug: Enzalutamide
    • Drug: Leuprolide
    • Drug: Dutasteride
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
52
November 2013
November 2013   (final data collection date for primary outcome measure)

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
Male
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT01547299
MDV3100-07
No
Medivation, Inc.
Medivation, Inc.
Astellas Pharma Inc
Not Provided
Medivation, Inc.
March 2015

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