Study of Enzalutamide (Formerly MDV3100) as a Neoadjuvant Therapy for Patients Undergoing Prostatectomy for Localized Prostate Cancer
Study Details
Study Description
Brief Summary
The purpose of this study is to determine if enzalutamide is an effective therapy in treating localized prostate cancer prior to prostatectomy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Enzalutamide alone Enzalutamide 160 mg, orally, once daily |
Drug: Enzalutamide
Other Names:
|
| 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 Names:
Drug: Leuprolide
Drug: Dutasteride
|
Outcome Measures
Primary Outcome Measures
- Pathologic Complete Response Rate [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.
Secondary Outcome Measures
- Percentage of Participants With Positive Surgical Margins [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 [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 [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 [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 [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 [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 [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) [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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) [Day 180]
To determine pharmacodynamic effects as measured by the amount of tissue DHT in prostatectomy specimens following radical prostatectomy.
- Pharmacodynamic Effects: Tissue Testosterone [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 [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 [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 [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 [Baseline]
- Serum Dihydrotestosterone (DHT): Day 180 [Day 180]
- Change From Baseline in Serum Dihydrotestosterone (DHT) at Day 180 [Day 180]
To determine serum hormone effects as measured by change in DHT values from baseline to the completion of therapy.
- Serum Testosterone: Baseline [Baseline]
- Serum Testosterone: Day 180 [Day 180]
- Change From Baseline in Serum Testosterone at Day 180 [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 [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.
Eligibility Criteria
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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Boston | Massachusetts | United States | 02215 | |
| 2 | Seattle | Washington | United States | 98195 | |
| 3 | Vancouver | British Columbia | Canada | V5Z 1M9 | |
| 4 | Toronto | Ontario | Canada | M5G 2M9 |
Sponsors and Collaborators
- Pfizer
- Astellas Pharma Inc
- Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- MDV3100-07
- C3431019
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Period Title: Overall Study | ||
| STARTED | 25 | 27 |
| COMPLETED | 23 | 25 |
| NOT COMPLETED | 2 | 2 |
Baseline Characteristics
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide | Total |
|---|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. | Total of all reporting groups |
| Overall Participants | 25 | 27 | 52 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
60.8
(6.95)
|
61.4
(7.65)
|
61.1
(7.26)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
0
0%
|
0
0%
|
0
0%
|
| Male |
25
100%
|
27
100%
|
52
100%
|
Outcome Measures
| Title | Pathologic Complete Response Rate |
|---|---|
| Description | 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. |
| Time Frame | Day 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 23 | 25 |
| Local pathologist |
8.7
34.8%
|
0.0
0%
|
| Central pathologist |
4.3
17.2%
|
0.0
0%
|
| Title | Percentage of Participants With Positive Surgical Margins |
|---|---|
| Description | 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. |
| Time Frame | Day 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 23 | 25 |
| Local pathologist |
4.3
17.2%
|
12.0
44.4%
|
| Central pathologist |
21.7
86.8%
|
16.0
59.3%
|
| Title | Percentage of Participants With Extracapsular Extension: Local Review |
|---|---|
| Description | 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. |
| Time Frame | Day 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 23 | 25 |
| Number (95% Confidence Interval) [percentage of participants] |
26.1
104.4%
|
36.0
133.3%
|
| Title | Percentage of Participants With Extracapsular Extension: Central Review |
|---|---|
| Description | 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. |
| Time Frame | Day 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 23 | 24 |
| Number (95% Confidence Interval) [percentage of participants] |
56.5
226%
|
70.8
262.2%
|
| Title | Percentage of Participants With Positive Seminal Vesicles |
|---|---|
| Description | 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. |
| Time Frame | Day 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 23 | 25 |
| Local pathologist |
30.4
121.6%
|
36.0
133.3%
|
| Central pathologist |
30.4
121.6%
|
36.0
133.3%
|
| Title | Percentage of Participants With Positive Lymph Nodes |
|---|---|
| Description | 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. |
| Time Frame | Day 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 23 | 25 |
| Local pathologist |
26.1
104.4%
|
4.0
14.8%
|
| Central pathologist |
26.1
104.4%
|
4.0
14.8%
|
| Title | Prostate-Specific Antigen (PSA) Nadir |
|---|---|
| Description | 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 Frame | Day 195 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 24 | 25 |
| Median (Full Range) [microgram per liter (mcg/L)] |
0.04
|
0.51
|
| Title | Time to Prostate-Specific Antigen (PSA) Nadir |
|---|---|
| Description | 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. |
| Time Frame | Day 195 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants randomly assigned to study treatment (intent-to-treat population) with a baseline PSA and at least one post baseline PSA. |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 25 | 27 |
| Median (Full Range) [days] |
5.09
|
6.01
|
| Title | Percentage of Participants With Reduction in Prostate-Specific Antigen (PSA) |
|---|---|
| Description | 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. |
| Time Frame | Day 195 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants randomly assigned to study treatment (intent-to-treat population) with a baseline PSA and at least one post baseline PSA. |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 25 | 27 |
| PSA < 0.2 ng/mL |
92.0
368%
|
29.6
109.6%
|
| 50% decrease in PSA |
100.0
400%
|
100.0
370.4%
|
| 90% decrease in PSA |
100.0
400%
|
63.0
233.3%
|
| Title | Health-Related Quality of Life (HRQoL): Number of Participants With The Expanded Prostate Cancer Index Composite (EPIC) Sexual Domain Summary Score |
|---|---|
| Description | 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. |
| Time Frame | Day 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 16 | 16 |
| Worsened |
11
44%
|
10
37%
|
| Stable |
4
16%
|
6
22.2%
|
| Improved |
1
4%
|
0
0%
|
| Title | Health-Related Quality of Life (HRQoL): Number of Participants With Expanded Prostate Cancer Index Composite (EPIC) Sexual Function Subscale Score |
|---|---|
| Description | 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. |
| Time Frame | Day 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 15 | 17 |
| Worsened |
11
44%
|
12
44.4%
|
| Stable |
4
16%
|
5
18.5%
|
| Improved |
0
0%
|
0
0%
|
| Title | Health-Related Quality of Life (HRQoL): Number of Participants With Expanded Prostate Cancer Index Composite (EPIC) Sexual Bother Subscale Score |
|---|---|
| Description | 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. |
| Time Frame | Day 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 16 | 16 |
| Worsened |
7
28%
|
5
18.5%
|
| Stable |
9
36%
|
7
25.9%
|
| Improved |
0
0%
|
4
14.8%
|
| Title | Health-Related Quality of Life (HRQoL): Number of Participants With Expanded Prostate Cancer Index Composite (EPIC) Hormonal Domain Summary Score |
|---|---|
| Description | 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. |
| Time Frame | Day 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 16 | 18 |
| Worsened |
10
40%
|
10
37%
|
| Stable |
3
12%
|
7
25.9%
|
| Improved |
3
12%
|
1
3.7%
|
| Title | Health-Related Quality of Life (HRQoL): Number of Participants With Expanded Prostate Cancer Index Composite (EPIC) Hormonal Function Subscale Score |
|---|---|
| Description | 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. |
| Time Frame | Day 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 16 | 18 |
| Worsened |
11
44%
|
11
40.7%
|
| Stable |
2
8%
|
7
25.9%
|
| Improved |
3
12%
|
0
0%
|
| Title | Health-Related Quality of Life (HRQoL): Number of Participants With Expanded Prostate Cancer Index Composite (EPIC) Hormonal Bother Subscale Score |
|---|---|
| Description | 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. |
| Time Frame | Day 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 16 | 18 |
| Worsened |
9
36%
|
6
22.2%
|
| Stable |
5
20%
|
11
40.7%
|
| Improved |
2
8%
|
1
3.7%
|
| Title | Health-Related Quality of Life (HRQoL): Number of Participants With Twelve-Item Short Form Version 2 General Health Domain Score |
|---|---|
| Description | 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. |
| Time Frame | Day 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 16 | 18 |
| Worsened |
5
20%
|
5
18.5%
|
| Stable |
9
36%
|
6
22.2%
|
| Improved |
2
8%
|
7
25.9%
|
| Title | Health-Related Quality of Life (HRQoL): Number of Participants With Twelve-Item Short Form Version 2 Physical Functioning Domain Score |
|---|---|
| Description | 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. |
| Time Frame | Day 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 16 | 18 |
| Worsened |
3
12%
|
2
7.4%
|
| Stable |
12
48%
|
15
55.6%
|
| Improved |
1
4%
|
1
3.7%
|
| Title | Health-Related Quality of Life (HRQoL): Number of Participants With Twelve-Item Short Form Version 2 Role-Emotional Domain Score |
|---|---|
| Description | 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. |
| Time Frame | Day 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 16 | 18 |
| Worsened |
3
12%
|
1
3.7%
|
| Stable |
9
36%
|
10
37%
|
| Improved |
4
16%
|
7
25.9%
|
| Title | Health-Related Quality of Life (HRQoL): Number of Participants With Twelve-Item Short Form Version 2 Mental Component Summary |
|---|---|
| Description | 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. |
| Time Frame | Day 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 16 | 17 |
| Worsened |
4
16%
|
1
3.7%
|
| Stable |
8
32%
|
11
40.7%
|
| Improved |
4
16%
|
5
18.5%
|
| Title | Pharmacodynamic Effects: Tissue Dihydrotestosterone (DHT) |
|---|---|
| Description | To determine pharmacodynamic effects as measured by the amount of tissue DHT in prostatectomy specimens following radical prostatectomy. |
| Time Frame | Day 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 23 | 25 |
| Mean (Standard Deviation) [picogram per milligram] |
0.04
(0.01)
|
3.34
(1.57)
|
| Title | Pharmacodynamic Effects: Tissue Testosterone |
|---|---|
| Description | To determine pharmacodynamic effects as measured by the amount of tissue testosterone in prostatectomy specimens following radical prostatectomy. |
| Time Frame | Day 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 23 | 25 |
| Mean (Standard Deviation) [picogram per milligram] |
0.18
(0.13)
|
0.90
(0.86)
|
| Title | Pharmacodynamic Effects: Assessment of Apoptosis |
|---|---|
| Description | 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. |
| Time Frame | Day 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data for this outcome measure was not collected as assessment of apoptosis was not performed due to limited amounts of tissue samples available. |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 0 | 0 |
| Title | Pharmacodynamic Effects: Assessment of Mitotic Index |
|---|---|
| Description | 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. |
| Time Frame | Day 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 22 | 25 |
| Mean (Standard Deviation) [ratio] |
0.9
(1.51)
|
2.6
(2.81)
|
| Title | Pharmacodynamic Effects: Assessment of Androgen Receptor Signaling as Measured by Intensity of Androgen Receptor Immunohistochemical (IHC) Staining |
|---|---|
| Description | 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. |
| Time Frame | Day 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants randomly assigned to study treatment (intent-to-treat population) with a prostatectomy sample evaluated by the local pathologist. |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 25 | 27 |
| 0 |
0.0
0%
|
0.0
0%
|
| 1 |
5.6
22.4%
|
0.0
0%
|
| 2 |
27.8
111.2%
|
5.3
19.6%
|
| 3 |
66.7
266.8%
|
94.7
350.7%
|
| Title | Serum Dihydrotestosterone (DHT): Baseline |
|---|---|
| Description | |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 23 | 27 |
| Median (Full Range) [ng/mL] |
0.34
|
0.29
|
| Title | Serum Dihydrotestosterone (DHT): Day 180 |
|---|---|
| Description | |
| Time Frame | Day 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 25 | 25 |
| Median (Full Range) [ng/mL] |
0.01
|
0.51
|
| Title | Change From Baseline in Serum Dihydrotestosterone (DHT) at Day 180 |
|---|---|
| Description | To determine serum hormone effects as measured by change in DHT values from baseline to the completion of therapy. |
| Time Frame | Day 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 23 | 25 |
| Median (Full Range) [ng/mL] |
-0.33
|
0.25
|
| Title | Serum Testosterone: Baseline |
|---|---|
| Description | |
| Time Frame | Baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 23 | 27 |
| Median (Full Range) [ng/mL] |
4.10
|
3.69
|
| Title | Serum Testosterone: Day 180 |
|---|---|
| Description | |
| Time Frame | Day 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 25 | 25 |
| Median (Full Range) [ng/mL] |
0.12
|
9.76
|
| Title | Change From Baseline in Serum Testosterone at Day 180 |
|---|---|
| Description | To determine serum hormone effects as measured by change in testosterone at baseline and at completion of therapy. |
| Time Frame | Day 180 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 23 | 25 |
| Median (Full Range) [ng/mL] |
-4.00
|
5.74
|
| Title | Number of Participants With Adverse Events (AEs) That Led to Dose Interruption, Dose Reduction, and Study Drug Discontinuation |
|---|---|
| Description | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. |
| Time Frame | From baseline up to 210 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 partial dose of enzalutamide (safety population). |
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide |
|---|---|---|
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. |
| Measure Participants | 25 | 27 |
| Permanent Discontinuation of Enzalutamide |
0
0%
|
0
0%
|
| Temporary Interruption of Enzalutamide |
3
12%
|
0
0%
|
| Dose Reduction of Enzalutamide |
0
0%
|
0
0%
|
| Study Drug Discontinuation |
0
0%
|
0
0%
|
Adverse Events
| Time Frame | From baseline to 30 days after the last dose of study drug, up to 210 days. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | 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. | |||
| Arm/Group Title | Enzalutamide + Leuprolide + Dutasteride | Enzalutamide | ||
| Arm/Group Description | 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. | Participants were administered 160 mg of Enzalutamide orally once daily for up to 180 days. | ||
All Cause Mortality |
||||
| Enzalutamide + Leuprolide + Dutasteride | Enzalutamide | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Enzalutamide + Leuprolide + Dutasteride | Enzalutamide | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/25 (12%) | 2/27 (7.4%) | ||
| Infections and infestations | ||||
| Pelvic abscess | 0/25 (0%) | 1/27 (3.7%) | ||
| Clostridial infection | 1/25 (4%) | 0/27 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Postoperative ileus | 1/25 (4%) | 0/27 (0%) | ||
| Vascular disorders | ||||
| Lymphocele | 1/25 (4%) | 1/27 (3.7%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Enzalutamide + Leuprolide + Dutasteride | Enzalutamide | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 25/25 (100%) | 27/27 (100%) | ||
| Gastrointestinal disorders | ||||
| Diarrhoea | 6/25 (24%) | 5/27 (18.5%) | ||
| Constipation | 4/25 (16%) | 2/27 (7.4%) | ||
| Nausea | 4/25 (16%) | 2/27 (7.4%) | ||
| Abdominal pain | 2/25 (8%) | 0/27 (0%) | ||
| Haematochezia | 0/25 (0%) | 2/27 (7.4%) | ||
| Rectal haemorrhage | 0/25 (0%) | 2/27 (7.4%) | ||
| General disorders | ||||
| Fatigue | 15/25 (60%) | 19/27 (70.4%) | ||
| Oedema peripheral | 2/25 (8%) | 2/27 (7.4%) | ||
| Pyrexia | 2/25 (8%) | 2/27 (7.4%) | ||
| Chills | 2/25 (8%) | 1/27 (3.7%) | ||
| Infections and infestations | ||||
| Nasopharyngitis | 4/25 (16%) | 2/27 (7.4%) | ||
| Sinusitis | 3/25 (12%) | 1/27 (3.7%) | ||
| Urinary tract infection | 3/25 (12%) | 1/27 (3.7%) | ||
| Diverticulitis | 2/25 (8%) | 1/27 (3.7%) | ||
| Upper respiratory tract infection | 2/25 (8%) | 1/27 (3.7%) | ||
| Injury, poisoning and procedural complications | ||||
| Incision site pain | 4/25 (16%) | 5/27 (18.5%) | ||
| Investigations | ||||
| Oestradiol increased | 0/25 (0%) | 3/27 (11.1%) | ||
| Weight decreased | 1/25 (4%) | 2/27 (7.4%) | ||
| Alanine aminotransferase increased | 2/25 (8%) | 0/27 (0%) | ||
| Aspartate aminotransferase increased | 2/25 (8%) | 0/27 (0%) | ||
| Blood creatinine increased | 0/25 (0%) | 2/27 (7.4%) | ||
| Weight increased | 0/25 (0%) | 2/27 (7.4%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 2/25 (8%) | 3/27 (11.1%) | ||
| Hypokalaemia | 1/25 (4%) | 3/27 (11.1%) | ||
| Hyperglycaemia | 1/25 (4%) | 2/27 (7.4%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Myalgia | 4/25 (16%) | 0/27 (0%) | ||
| Musculoskeletal pain | 2/25 (8%) | 1/27 (3.7%) | ||
| Arthralgia | 2/25 (8%) | 0/27 (0%) | ||
| Nervous system disorders | ||||
| Headache | 3/25 (12%) | 3/27 (11.1%) | ||
| Memory impairment | 3/25 (12%) | 3/27 (11.1%) | ||
| Restless leg syndrome | 3/25 (12%) | 3/27 (11.1%) | ||
| Amnesia | 0/25 (0%) | 3/27 (11.1%) | ||
| Mental impairment | 1/25 (4%) | 2/27 (7.4%) | ||
| Psychiatric disorders | ||||
| Insomnia | 9/25 (36%) | 6/27 (22.2%) | ||
| Libido decreased | 8/25 (32%) | 4/27 (14.8%) | ||
| Anxiety | 4/25 (16%) | 1/27 (3.7%) | ||
| Depression | 2/25 (8%) | 1/27 (3.7%) | ||
| Renal and urinary disorders | ||||
| Pollakiuria | 6/25 (24%) | 4/27 (14.8%) | ||
| Urinary incontinence | 2/25 (8%) | 5/27 (18.5%) | ||
| Incontinence | 3/25 (12%) | 3/27 (11.1%) | ||
| Nocturia | 3/25 (12%) | 1/27 (3.7%) | ||
| Dysuria | 0/25 (0%) | 2/27 (7.4%) | ||
| Micturition urgency | 2/25 (8%) | 0/27 (0%) | ||
| Urinary retention | 0/25 (0%) | 2/27 (7.4%) | ||
| Reproductive system and breast disorders | ||||
| Gynaecomastia | 3/25 (12%) | 17/27 (63%) | ||
| Breast tenderness | 2/25 (8%) | 9/27 (33.3%) | ||
| Erectile dysfunction | 2/25 (8%) | 6/27 (22.2%) | ||
| Breast pain | 0/25 (0%) | 7/27 (25.9%) | ||
| Nipple pain | 1/25 (4%) | 3/27 (11.1%) | ||
| Penile pain | 2/25 (8%) | 0/27 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 1/25 (4%) | 2/27 (7.4%) | ||
| Nasal congestion | 0/25 (0%) | 2/27 (7.4%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Dry skin | 0/25 (0%) | 3/27 (11.1%) | ||
| Vascular disorders | ||||
| Hot flush | 24/25 (96%) | 7/27 (25.9%) | ||
| Hypertension | 3/25 (12%) | 3/27 (11.1%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
PI agrees not to independently publish the results before the publication of the multi-center PI paper. Sponsor shall review and comment 30 days prior to submission or disclosure. If publication or disclosure contains Sponsor Confidential Information, other than study data, PI agrees to remove Confidential Information from publication or disclosure. Sponsor may request that PI delay such publication for an additional 60 days to protect the patentability of any invention described.
Results Point of Contact
| Name/Title | William Novotny, MD, Sr. Director, Clinical Development |
|---|---|
| Organization | Medivation, Inc. |
| Phone | 415- 983-3066 |
| william.novotny@medivation.com |
- MDV3100-07
- C3431019