Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antineoplastic Agents

Reproductive Control Agents

All Drugs and Chemicals

Leuprolide

Dutasteride

Antineoplastic Agents, Hormonal

5-alpha Reductase Inhibitors

Enzyme Inhibitors

Hormones

Hormone Antagonists

Enzalutamide 160 mg, orally, once daily and leuprolide 22.5 mg, intramuscular injection, every 3 months, and dutasteride, 0.5 mg, orally, once daily

Enzalutamide

Pfizer CT.gov Call Center

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

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

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

To determine pharmacodynamic effects as measured by the amount of tissue DHT in prostatectomy specimens following radical prostatectomy.

To determine pharmacodynamic effects as measured by the amount of tissue testosterone in prostatectomy specimens following radical prostatectomy.

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.

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.

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.

To determine serum hormone effects as measured by change in DHT values from baseline to the completion of therapy.

To determine serum hormone effects as measured by change in testosterone at baseline and at completion of therapy.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.

Astellas Pharma Inc

Medivation LLC, a wholly owned subsidiary of Pfizer Inc.

Pfizer

Same event may appear as AE and serious AE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another or 1 participant may have experienced both serious and non-serious event during study. Safety data set included all participants who received at least one partial dose of study drug.

Participants were administered 160 mg of Enzalutamide orally once daily, 22.5 mg of Leuprolide every 3 months through intramuscular injection and 0.5 mg of Dutasteride orally once daily for up to 180 days.

Enzalutamide + Leuprolide + Dutasteride

Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days.

Total

Age, Continuous

Sex: Female, Male

William Novotny, MD, Sr. Director, Clinical Development

Local pathologist

Central pathologist

All participants randomly assigned to study treatment (intent-to-treat population) with a prostatectomy sample evaluated by the local and central pathologist. Here, "N" signifies number of participants evaluable for this specified outcome measure.

Pathologic Complete Response Rate

Percentage of Participants With Positive Surgical Margins

All participants randomly assigned to study treatment (intent-to-treat population) with a prostatectomy sample evaluated by the local pathologist. Here, "N" signifies number of participants evaluable for this specified outcome measure.

Percentage of Participants With Extracapsular Extension: Local Review

All participants randomly assigned to study treatment with a prostatectomy sample evaluated by the central pathologist. One participant in the Enzalutamide treatment arm was excluded from the analysis because the result reported by the central lab was indeterminate. Here, "N" signifies number of participants evaluable for this outcome measure.

Percentage of Participants With Extracapsular Extension: Central Review

Percentage of Participants With Positive Seminal Vesicles

Percentage of Participants With Positive Lymph Nodes

All participants randomly assigned to study treatment (intent-to-treat population) with a baseline PSA and at least one post baseline PSA. Here, "N" signifies number of participants evaluable for this specified outcome measure.

Prostate-Specific Antigen (PSA) Nadir

All participants randomly assigned to study treatment (intent-to-treat population) with a baseline PSA and at least one post baseline PSA.

Time to Prostate-Specific Antigen (PSA) Nadir

PSA < 0.2 ng/mL

50% decrease in PSA

90% decrease in PSA

Percentage of Participants With Reduction in Prostate-Specific Antigen (PSA)

Worsened

Stable

Improved

All participants randomly assigned to study treatment (intent-to-treat population) with a baseline and at least one post baseline score. Here, "N" signifies number of participants evaluable for this specified outcome measure.

Health-Related Quality of Life (HRQoL): Number of Participants With The Expanded Prostate Cancer Index Composite (EPIC) Sexual Domain Summary Score

Health-Related Quality of Life (HRQoL): Number of Participants With Expanded Prostate Cancer Index Composite (EPIC) Sexual Function Subscale Score

Health-Related Quality of Life (HRQoL): Number of Participants With Expanded Prostate Cancer Index Composite (EPIC) Sexual Bother Subscale Score

Health-Related Quality of Life (HRQoL): Number of Participants With Expanded Prostate Cancer Index Composite (EPIC) Hormonal Domain Summary Score

Health-Related Quality of Life (HRQoL): Number of Participants With Expanded Prostate Cancer Index Composite (EPIC) Hormonal Function Subscale Score

Health-Related Quality of Life (HRQoL): Number of Participants With Expanded Prostate Cancer Index Composite (EPIC) Hormonal Bother Subscale Score

Health-Related Quality of Life (HRQoL): Number of Participants With Twelve-Item Short Form Version 2 General Health Domain Score

Health-Related Quality of Life (HRQoL): Number of Participants With Twelve-Item Short Form Version 2 Physical Functioning Domain Score

Health-Related Quality of Life (HRQoL): Number of Participants With Twelve-Item Short Form Version 2 Role-Emotional Domain Score

Health-Related Quality of Life (HRQoL): Number of Participants With Twelve-Item Short Form Version 2 Mental Component Summary

All participants randomly assigned to study treatment (intent-to-treat population) with a prostatectomy sample evaluated by the central pathologist. Here, "N" signifies number of participants evaluable for this specified outcome measure.

Pharmacodynamic Effects: Tissue Dihydrotestosterone (DHT)

Pharmacodynamic Effects: Tissue Testosterone

Data for this outcome measure was not collected as assessment of apoptosis was not performed due to limited amounts of tissue samples available.

Pharmacodynamic Effects: Assessment of Apoptosis

Pharmacodynamic Effects: Assessment of Mitotic Index

All participants randomly assigned to study treatment (intent-to-treat population) with a prostatectomy sample evaluated by the local pathologist.

Pharmacodynamic Effects: Assessment of Androgen Receptor Signaling as Measured by Intensity of Androgen Receptor Immunohistochemical (IHC) Staining

All participants randomly assigned to study treatment (intent-to-treat population) with a baseline serum DHT result. Here, "N" signifies number of participants evaluable for this specified outcome measure.

Serum Dihydrotestosterone (DHT): Baseline

All participants randomly assigned to study treatment (intent-to-treat population) with 180 days post baseline serum DHT result. Here, "N" signifies number of participants evaluable for this specified outcome measure.

Serum Dihydrotestosterone (DHT): Day 180

All participants randomly assigned to study treatment (intent-to-treat population) with a serum DHT result at baseline and 180 days post baseline. Here, "N" signifies number of participants evaluable for this specified outcome measure.

Change From Baseline in Serum Dihydrotestosterone (DHT) at Day 180

All participants randomly assigned to study treatment (intent-to-treat population) with a baseline serum testosterone result. Here, "N" signifies number of participants evaluable for this specified outcome measure.

Serum Testosterone: Baseline

All participants randomly assigned to study treatment (intent-to-treat population) with a 180 days post baseline serum testosterone result. Here, "N" signifies number of participants evaluable for this specified outcome measure.

Serum Testosterone: Day 180

All participants randomly assigned to study treatment (intent-to-treat population) with a serum testosterone result at baseline and 180 days post baseline. Here, "N" signifies number of participants evaluable for this specified outcome measure.

Change From Baseline in Serum Testosterone at Day 180

Permanent Discontinuation of Enzalutamide

Temporary Interruption of Enzalutamide

Dose Reduction of Enzalutamide

Study Drug Discontinuation

All participants who received at least 1 partial dose of enzalutamide (safety population).

Number of Participants With Adverse Events (AEs) That Led to Dose Interruption, Dose Reduction, and Study Drug Discontinuation

Participants were administered 160 milligram (mg) of Enzalutamide orally once daily, 22.5 mg of Leuprolide every 3 months through intramuscular injection and 0.5 mg of Dutasteride orally once daily for up to 180 days.

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

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