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

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ClinicalTrials.gov Identifier: NCT01547299
Recruitment Status : Completed
First Posted : March 7, 2012
Results First Posted : April 10, 2015
Last Update Posted : December 20, 2017
Sponsor:
Collaborators:
Astellas Pharma Inc
Medivation, Inc.
Information provided by (Responsible Party):
Pfizer

February 27, 2012
March 7, 2012
March 30, 2015
April 10, 2015
December 20, 2017
March 31, 2012
November 30, 2013   (Final data collection date for primary outcome measure)
Pathologic Complete Response Rate [ Time Frame: Day 180 ]
Pathologic complete response rate was defined as percentage of participants with pathologic complete response. Pathologic complete response rate following triplet therapy (enzalutamide in combination with leuprolide and dutasteride) and enzalutamide alone when administered as neoadjuvant therapy for 180 days prior to prostatectomy in participants with localized prostate cancer. Pathologic complete response was defined as the absence of morphologically identifiable carcinoma in the prostatectomy specimen, as assessed by the local and central pathologist.
Pathological Complete Response Rate [ Time Frame: 6 months ]
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 Participants With Positive Surgical Margins [ Time Frame: Day 180 ]
    To determine the percentage of participants with positive surgical margins at prostatectomy as assessed by the local and central pathologist. Surgical margin, also known as tumor free margin referred to the visible normal tissue or skin margin that was removed with the surgical excision of a tumor, growth, or malignancy. The margin was described as positive when the pathologist finds cancer cells at the edge of the tissue, suggesting that all of the cancer has not been removed.
  • Percentage of Participants With Extracapsular Extension: Local Review [ Time Frame: Day 180 ]
    To determine the percentage of participants with extracapsular extension at prostatectomy as assessed by the local pathologist. Extracapsular extension was defined as prostate cancer cells when extended into the prostate capsule or outer lining of the prostate gland.
  • Percentage of Participants With Extracapsular Extension: Central Review [ Time Frame: Day 180 ]
    To determine the percentage of participants with extracapsular extension at prostatectomy as assessed by the central pathologist. Extracapsular extension was defined as prostate cancer cells when extended into the prostate capsule or outer lining of the prostate gland.
  • Percentage of Participants With Positive Seminal Vesicles [ Time Frame: Day 180 ]
    To determine the percentage of participants with positive seminal vesicles at prostatectomy as assessed by the local and central pathologist. Seminal vesicles or seminal glands, were defined as a pair of simple tubular glands located within the pelvis. They secrete fluid that partly composes the semen. Seminal vesicles with cancer cells in them were called positive seminal vesicles.
  • Percentage of Participants With Positive Lymph Nodes [ Time Frame: Day 180 ]
    To determine the percentage of participants with positive lymph nodes at prostatectomy as assessed by the local and central pathologist. Lymph nodes were small clumps of immune cells that act as filters for the lymphatic system. Lymph nodes with cancer cells in them were called positive lymph nodes.
  • Prostate-Specific Antigen (PSA) Nadir [ Time Frame: Day 195 ]
    To determine the effects on PSA as measured by the lowest post baseline PSA value prior to prostatectomy. Prostate-specific antigen (PSA) was a protein produced by normal, as well as malignant, cells of the prostate gland. The PSA nadir was the participant's lowest observed post baseline PSA value.
  • Time to Prostate-Specific Antigen (PSA) Nadir [ Time Frame: Day 195 ]
    To determine the effects on PSA as measured by the time to the lowest post baseline PSA value prior to prostatectomy. Prostate-specific antigen (PSA) was a protein produced by normal, as well as malignant, cells of the prostate gland. The PSA nadir was the participant's lowest observed post baseline PSA value.
  • Percentage of Participants With Reduction in Prostate-Specific Antigen (PSA) [ Time Frame: Day 195 ]
    To determine the effects on PSA as measured by the percentage of participants with PSA less than (<) 0.2 nanogram per milliliter (ng/mL), and a 50 percent (%) and 90% decrease in PSA value prior to prostatectomy. Prostate-specific antigen (PSA) was a protein produced by normal, as well as malignant, cells of the prostate gland.
  • Health-Related Quality of Life (HRQoL): Number of Participants With The Expanded Prostate Cancer Index Composite (EPIC) Sexual Domain Summary Score [ Time Frame: Day 180 ]
    EPIC sexual domain was HRQoL instrument that measured the effects of prostate cancer treatment on a participant's sexual function and sexual satisfaction. Sexual domain summary score was measured on a scale ranged from 0 (worst) to 100 (best) with higher scores representing better sexual function and satisfaction. Best change from baseline category in EPIC sexual domain summary score ranged from worsened to improved where worsened indicated decrease of at least 1 minimally important difference, stable indicated changed by less than 1 minimally important difference and improved indicated increase of at least 1 minimally important difference. Minimally important difference was defined as one-half of the standard deviation of baseline score. Number of participants within each category are reported below.
  • Health-Related Quality of Life (HRQoL): Number of Participants With Expanded Prostate Cancer Index Composite (EPIC) Sexual Function Subscale Score [ Time Frame: Day 180 ]
    EPIC sexual function subscale was HRQoL instrument that measured the effects of prostate cancer treatment on a participant's sexual function and sexual satisfaction. EPIC sexual function subscale was a component of sexual domain that was evaluated on a distinct set of questions. It was measured on a scale ranged from 0 (worst) to 100 (best) with higher scores representing better sexual function. Best change from baseline category in EPIC sexual function subscale score ranged from worsened to improved where worsened indicated decrease of at least 1 minimally important difference, stable indicated changed by less than 1 minimally important difference and improved indicated increase of at least 1 minimally important difference. Minimally important difference was defined as one-half of the standard deviation of baseline score. Number of participants within each category are reported below.
  • Health-Related Quality of Life (HRQoL): Number of Participants With Expanded Prostate Cancer Index Composite (EPIC) Sexual Bother Subscale Score [ Time Frame: Day 180 ]
    EPIC sexual bother subscale was HRQoL instrument that measured the effects of prostate cancer treatment on a participant's sexual function and sexual satisfaction. EPIC sexual bother subscale was a component of sexual domain that was evaluated on a distinct set of questions. It was measured on a scale ranged from 0 (worst) to 100 (best) with higher scores representing less sexual bother and difficulty. Best change from baseline category in EPIC sexual bother subscale score ranged from worsened to improved where worsened indicated decrease of at least 1 minimally important difference, stable indicated changed by less than 1 minimally important difference and improved indicated increase of at least 1 minimally important difference. Minimally important difference was defined as one-half of the standard deviation of baseline score. Number of participants within each category are reported below.
  • Health-Related Quality of Life (HRQoL): Number of Participants With Expanded Prostate Cancer Index Composite (EPIC) Hormonal Domain Summary Score [ Time Frame: Day 180 ]
    EPIC Hormonal Domain was HRQoL instrument that measured the effects of prostate cancer treatment on a participant's hormonal function. It was measured on a scale ranged from 0 (worst) to 100 (best) scale with higher scores representing better hormonal function. Best change from baseline category in EPIC hormonal domain summary score ranged from worsened to improved where worsened indicated decrease of at least 1 minimally important difference, stable indicated changed by less than 1 minimally important difference and improved indicated increase of at least 1 minimally important difference. Minimally important difference was defined as one-half of the standard deviation baseline score. Number of participants within each category are reported below.
  • Health-Related Quality of Life (HRQoL): Number of Participants With Expanded Prostate Cancer Index Composite (EPIC) Hormonal Function Subscale Score [ Time Frame: Day 180 ]
    EPIC hormonal function subscale score was HRQoL instrument that measured the effects of prostate cancer treatment on a participant's hormonal function. EPIC hormonal function subscale was a component of hormonal domain that was evaluated on a distinct set of questions. It was measured on a scale ranged from 0 (worst) to 100 (best) scale with higher scores representing better hormonal function. Best change from baseline category in EPIC hormonal function subscale score ranged from worsened to improved where worsened indicated decrease of at least 1 minimally important difference, stable indicated changed by less than 1 minimally important difference and improved indicated increase of at least 1 minimally important difference. Minimally important difference was defined as one-half of the standard deviation baseline score. Number of participants within each category are reported below.
  • Health-Related Quality of Life (HRQoL): Number of Participants With Expanded Prostate Cancer Index Composite (EPIC) Hormonal Bother Subscale Score [ Time Frame: Day 180 ]
    EPIC hormonal bother subscale score was HRQoL instrument that measured the effects of prostate cancer treatment on a participant's hormonal function. EPIC hormonal bother subscale was a component of hormonal domain that was evaluated on a distinct set of questions. It was measured on a scale ranged from 0 (worst) to 100 (best) scale with higher scores representing less hormonal bothering. Best change from baseline category in EPIC hormonal bother subscale score ranged from worsened to improved where worsened indicated decrease of at least 1 minimally important difference, stable indicated changed by less than 1 minimally important difference and improved indicated increase of at least 1 minimally important difference. Minimally important difference was defined as one-half of the standard deviation baseline score. Number of participants within each category are reported below.
  • Health-Related Quality of Life (HRQoL): Number of Participants With Twelve-Item Short Form Version 2 General Health Domain Score [ Time Frame: Day 180 ]
    The Twelve-Item Short Form Version 2 was HRQoL instrument that measured general health and well-being across physical and mental components. The general health domain score contained 1 item scored on a scale of 1 to 5 where 1=excellent to 5=poor health, where higher score indicated worse health status. Best change from baseline category in general health domain score ranged from 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 was defined as one-half the standard deviation of the score of interest at baseline.
  • Health-Related Quality of Life (HRQoL): Number of Participants With Twelve-Item Short Form Version 2 Physical Functioning Domain Score [ Time Frame: Day 180 ]
    The Twelve-Item Short Form Version 2 was HRQoL instrument that measured general health and well-being across physical and mental components. The physical functioning domain score contained 2 items each scored on a scale of 1 to 5 where 1=excellent physical functioning to 5=poor physical functioning. Physical functioning domain total score ranged from 1 to 10, where higher scores indicated poor physical functioning. Best change from baseline category in physical functioning domain score ranged from 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 was defined as one-half the standard deviation of the score of interest at baseline.
  • Health-Related Quality of Life (HRQoL): Number of Participants With Twelve-Item Short Form Version 2 Role-Emotional Domain Score [ Time Frame: Day 180 ]
    The Twelve-Item Short Form Version 2 was HRQoL instrument that measured general health and well-being across physical and mental components. The mental health domain score had 2 items scored on a scale of 1 to 5, where higher scores indicated worse mental status. The total score ranged from 1 to 10, where higher scores indicated worse mental status. Best change from baseline category in mental component summary ranged from 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 was defined as one-half the standard deviation of the score of interest at baseline.
  • Health-Related Quality of Life (HRQoL): Number of Participants With Twelve-Item Short Form Version 2 Mental Component Summary [ Time Frame: Day 180 ]
    The Twelve-Item Short Form Version 2 was HRQoL instrument that measured general health and well-being across physical and mental components. The mental health domain score had 2 items scored on a scale of 1 to 5 where for 1 item 1=all of the time person felt calm and peaceful to 5=none of the time person felt calm and peaceful. The score ranged from 1 to 5, where higher scores meant worse mental status. For other item 1=all of the time person felt downhearted and blue to 5=none of the time person felt downhearted and blue. The score ranged from 1 to 5, where higher scores meant better mental status. Best change from baseline category in mental component summary ranged from 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 was defined as one-half the standard deviation of the score of interest at baseline.
  • Pharmacodynamic Effects: Tissue Dihydrotestosterone (DHT) [ Time Frame: Day 180 ]
    To determine pharmacodynamic effects as measured by the amount of tissue DHT in prostatectomy specimens following radical prostatectomy.
  • Pharmacodynamic Effects: Tissue Testosterone [ Time Frame: Day 180 ]
    To determine pharmacodynamic effects as measured by the amount of tissue testosterone in prostatectomy specimens following radical prostatectomy.
  • Pharmacodynamic Effects: Assessment of Apoptosis [ Time Frame: Day 180 ]
    To determine the effects of triplet therapy and enzalutamide alone on apoptosis in prostatectomy specimens. Apoptosis was a process of biochemical events that lead to characteristic cell changes and death.
  • Pharmacodynamic Effects: Assessment of Mitotic Index [ Time Frame: Day 180 ]
    Assessment was performed to determine the effects of triplet therapy and enzalutamide alone on mitotic index. Mitotic index was defined as the ratio between the numbers of cells in a population undergoing mitosis to the number of cells in a population not undergoing mitosis in prostatectomy specimens.
  • Pharmacodynamic Effects: Assessment of Androgen Receptor Signaling as Measured by Intensity of Androgen Receptor Immunohistochemical (IHC) Staining [ Time Frame: Day 180 ]
    To determine the effects of triplet therapy and enzalutamide alone on androgen receptor signaling in prostatectomy specimens. Androgen receptor (AR) was a type of nuclear receptor that was activated by binding either of the androgenic hormones, testosterone, or dihydrotestosterone in the cytoplasm and then translocating into the nucleus. Androgen receptor (AR) signaling represented the major therapeutic target for treating metastatic prostate cancer. Assessment of androgen receptor signaling was measured by intensity of androgen receptor IHC staining and were graded as 0 (absent), 1 (weak), 2 (moderate) and 3 (strong). Percentage of participants within each grade are reported below.
  • Serum Dihydrotestosterone (DHT): Baseline [ Time Frame: Baseline ]
  • Serum Dihydrotestosterone (DHT): Day 180 [ Time Frame: Day 180 ]
  • Change From Baseline in Serum Dihydrotestosterone (DHT) at Day 180 [ Time Frame: Day 180 ]
    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 ]
  • Serum Testosterone: Day 180 [ Time Frame: Day 180 ]
  • Change From Baseline in Serum Testosterone at Day 180 [ Time Frame: Day 180 ]
    To determine serum hormone effects as measured by change in testosterone at baseline and at completion of therapy.
  • Number of Participants With Adverse Events (AEs) That Led to Dose Interruption, Dose Reduction, and Study Drug Discontinuation [ Time Frame: From baseline up to 210 days ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
  • PSA [ Time Frame: 6 months ]
    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 ]
    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 ]
    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 ]
    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 ]
    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
Intervention Model: Parallel Assignment
Masking: None (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
50
November 30, 2013
November 30, 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
Sexes Eligible for Study: Male
Gender Based Eligibility: Yes
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Canada,   United States
 
 
NCT01547299
MDV3100-07
C3431019 ( Other Identifier: Alias Study Number )
No
Not Provided
Plan to Share IPD: Yes
Plan Description: Information relating to our policy on data sharing and the process for requesting data can be found at the following link: http://www.pfizer.com/research/clinical_trials/trial_data_and_results/data_requests
URL: http://
Pfizer
Pfizer
  • Astellas Pharma Inc
  • Medivation, Inc.
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
November 2017

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