Clinical Trials List
Protocol Number9785-CL-0335
NCT Number(ClinicalTrials.gov Identfier)NCT02677896
2016-08-01 - 2024-12-31
Phase III
Terminated5
ICD-10C61
Malignant neoplasm of prostate
ICD-9185
Malignant neoplasm of prostate
A Multinational, Phase 3, Randomized, Double-blind, Placebo-controlled Efficacy and Safety Study of Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Patients with Metastatic Hormone Sensitive Prostate Cancer (mHSPC)
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Trial Applicant
PPD DEVELOPMENT (HK) LIMITED
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Sponsor
Astellas Pharma Global Development, Inc.
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Chuan-Shu Chen Division of Urology
- Chia-Yen Lin Division of Urology
- Cheng-Che Chen Division of Urology
- Cheng-Kuang Yang Division of Urology
- 裘坤元 Division of Urology
- Shian-Shiang Wang Division of Urology
- 蔡世傳 Division of Nuclear Medicine
- 洪啟峰 Division of Urology
- 熊小澐 Division of Radiology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Tzu-chun Wei Division of Urology
- Yi-Hsiu Huang Division of Urology
- Tzu-Ping Lin Division of Urology
- 沈書慧 Division of Radiology
- Hsiao-Jen Chung Division of Urology
- 朱力行 Division of Nuclear Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Hsiang Ying Lee Division of Urology
- 黃俊農 Division of Urology
- Tsung-Yi Huang Division of Urology
The Actual Total Number of Participants Enrolled
0 Terminated
Linkou Chang Gung Medical Foundation
Taiwan National PI
馮思中
Co-Principal Investigator
- Yung-Chang Lin Division of Hematology & Oncology
- Rita cheng Division of Hematology & Oncology
- 張英勛 Division of Hematology & Oncology
- 黃成之 Division of Radiology
- 劉忠一 Division of Hematology & Oncology
- Jing-Ren Tseng Division of Nuclear Medicine
The Actual Total Number of Participants Enrolled
7 Terminated
Audit
None
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- 戴逸昇 Division of Urology
- CHING-CHU LU Division of Nuclear Medicine
- CHUNG-HSIN CHEN Division of Urology
- Ying-Chun Shen Division of Hematology & Oncology
- 劉詩彬 Division of Urology
- 葉亭均 Division of Urology
- 陳育青 Division of Radiology
- - - Division of Urology
- Yu-Chieh Tsai Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
Metastatic Hormone Sensitive Prostate Cancer (mHSPC)
Objectives
The objective of this phase 3 study is to evaluate the efficacy and safety of enzalutamide plus ADT
versus placebo plus ADT in subjects with mHSPC.
Primary Objective
To determine the benefit of enzalutamide plus ADT as compared to placebo plus ADT as
assessed by radiographic progression-free survival (rPFS) based on central review
Secondary Objectives
To determine the benefit of enzalutamide plus ADT as compared to placebo plus ADT as
assessed by overall survival (OS)
To determine the benefit of enzalutamide plus ADT as compared to placebo plus ADT as
assessed by time to first Symptomatic Skeletal Event (SSE)
To determine the benefit of enzalutamide plus ADT as compared to placebo plus ADT as
assessed by time to castration resistance
To determine the benefit of enzalutamide plus ADT as compared to placebo plus ADT as
assessed by Quality of Life (QoL) (as measured by Quality of Life Prostate-specific
Questionnaire [QLQ-PR25] / Functional Assessment of Cancer Therapy-Prostate [FACT-P]
and EuroQol Group-5 Dimension-5 Level Instrument [EQ-5D-5L])
To determine the benefit of enzalutamide plus ADT as compared to placebo plus ADT as
assessed by time to start of new antineoplastic therapy
To determine the benefit of enzalutamide plus ADT as compared to placebo plus ADT as
assessed by time to prostate-specific antigen (PSA) progression
To determine the benefit of enzalutamide plus ADT as compared to placebo plus ADT as
assessed by PSA undetectable rate (< 0.2 ng/mL)
To determine the benefit of enzalutamide plus ADT as compared to placebo plus ADT as
assessed by objective response rate (ORR)
To determine the benefit of enzalutamide plus ADT as compared to placebo plus ADT as
assessed by worsening of pain (as measured by Brief Pain Inventory-Short Form [BPI-SF])
Test Drug
Xtandi® Soft Capsules 40 mg
Active Ingredient
Enzalutamide
Dosage Form
Soft Capsule
Dosage
40mg
Endpoints
Primary Endpoints
rPFS (based on central review)
Secondary Endpoints
OS
Time to first SSE
Time to castration resistance
Time to deterioration of QoL
Time to initiation of new antineoplastic therapy
Time to PSA progression (≥ 2 ng/mL) (Prostate Cancer Clinical Trials Working Group 2 criteria)
PSA undetectable rate (< 0.2 ng/mL)
ORR
Time to pain progression
Safety Endpoints
Nature, frequency and severity of adverse events
Safety laboratory tests: biochemistry and hematology
Physical examination
ECG
Vital signs (blood pressure, pulse and temperature)
rPFS (based on central review)
Secondary Endpoints
OS
Time to first SSE
Time to castration resistance
Time to deterioration of QoL
Time to initiation of new antineoplastic therapy
Time to PSA progression (≥ 2 ng/mL) (Prostate Cancer Clinical Trials Working Group 2 criteria)
PSA undetectable rate (< 0.2 ng/mL)
ORR
Time to pain progression
Safety Endpoints
Nature, frequency and severity of adverse events
Safety laboratory tests: biochemistry and hematology
Physical examination
ECG
Vital signs (blood pressure, pulse and temperature)
Inclution Criteria
Inclusion:
Subject is eligible for the study if all of the following apply:
1. Institutional Review Board (IRB)-/Independent Ethics Committee (IEC)-approved written
informed consent and privacy language as per national regulations (e.g., Health Insurance
Portability Accountability Act authorization for United States sites) must be obtained from the
subject or legally authorized representative prior to any study-related procedures (including
withdrawal of prohibited medication, if applicable).
2. Subject is considered an adult according to local regulation at the time of signing informed
consent.
3. Subject is diagnosed with histologically or cytologically confirmed adenocarcinoma of the
prostate without neuroendocrine differentiation, signet cell or small cell histology. Specific to
subjects enrolled in France, histological diagnosis is required.
4. Subject has metastatic prostate cancer documented by positive bone scan or metastatic lesions on
CT or MRI scan. Subjects whose disease spread is limited to regional pelvic lymph nodes are
not eligible.
5. Once randomized at day 1, subject must maintain ADT with an LHRH agonist or antagonist
during study treatment or have a history of bilateral orchiectomy (i.e., medical or surgical
castration).
6. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at
screening.
7. Subject has an estimated life expectancy of ≥ 12 months as assessed by the Investigator.
8. Subject is able to swallow the study drug and comply with study requirements.
9. A sexually active male subject and his female partner who is of childbearing potential must use
2 acceptable methods of birth control (1 of which must include a condom as a barrier method of
contraception) from screening through 3 months after the last dose of study drug. Two
acceptable methods of birth control include condom (barrier method is required) AND 1 of the
following:
Consistent and correct usage of established, proper use of hormonal contraceptives that
inhibit ovulation by the female partner;
Established intrauterine device or intrauterine system by the female partner;
Tubal ligation in the female partner performed at least 6 months prior to subject’s screening
visit;
Vasectomy or other procedure resulting in infertility (e.g., bilateral orchiectomy) performed
at least 6 months prior to screening;
Calendar-based contraceptive methods (Knaus-Ogino or rhythm method applicable to
subjects enrolled in Japan only).
10. Subject must use a condom throughout the study if engaging in sexual intercourse with a
pregnant woman.
11. Subject must agree not to donate sperm from first dose of study drug through 3 months after the
last dose of study drug.
12. Subject agrees not to participate in another interventional study while on treatment.
Waivers to the inclusion criteria will NOT be allowed.
Subject is eligible for the study if all of the following apply:
1. Institutional Review Board (IRB)-/Independent Ethics Committee (IEC)-approved written
informed consent and privacy language as per national regulations (e.g., Health Insurance
Portability Accountability Act authorization for United States sites) must be obtained from the
subject or legally authorized representative prior to any study-related procedures (including
withdrawal of prohibited medication, if applicable).
2. Subject is considered an adult according to local regulation at the time of signing informed
consent.
3. Subject is diagnosed with histologically or cytologically confirmed adenocarcinoma of the
prostate without neuroendocrine differentiation, signet cell or small cell histology. Specific to
subjects enrolled in France, histological diagnosis is required.
4. Subject has metastatic prostate cancer documented by positive bone scan or metastatic lesions on
CT or MRI scan. Subjects whose disease spread is limited to regional pelvic lymph nodes are
not eligible.
5. Once randomized at day 1, subject must maintain ADT with an LHRH agonist or antagonist
during study treatment or have a history of bilateral orchiectomy (i.e., medical or surgical
castration).
6. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at
screening.
7. Subject has an estimated life expectancy of ≥ 12 months as assessed by the Investigator.
8. Subject is able to swallow the study drug and comply with study requirements.
9. A sexually active male subject and his female partner who is of childbearing potential must use
2 acceptable methods of birth control (1 of which must include a condom as a barrier method of
contraception) from screening through 3 months after the last dose of study drug. Two
acceptable methods of birth control include condom (barrier method is required) AND 1 of the
following:
Consistent and correct usage of established, proper use of hormonal contraceptives that
inhibit ovulation by the female partner;
Established intrauterine device or intrauterine system by the female partner;
Tubal ligation in the female partner performed at least 6 months prior to subject’s screening
visit;
Vasectomy or other procedure resulting in infertility (e.g., bilateral orchiectomy) performed
at least 6 months prior to screening;
Calendar-based contraceptive methods (Knaus-Ogino or rhythm method applicable to
subjects enrolled in Japan only).
10. Subject must use a condom throughout the study if engaging in sexual intercourse with a
pregnant woman.
11. Subject must agree not to donate sperm from first dose of study drug through 3 months after the
last dose of study drug.
12. Subject agrees not to participate in another interventional study while on treatment.
Waivers to the inclusion criteria will NOT be allowed.
Exclusion Criteria
Exclusion:
Subject will be excluded from participation if any of the following apply:
1. Subject has received any prior pharmacotherapy, radiation therapy or surgery for metastatic
prostate cancer (the following exceptions are permitted):
Up to 3 months of ADT with luteinizing hormone-releasing hormone (LHRH) agonists or
antagonists or orchiectomy with or without concurrent antiandrogens prior to day 1, with no
radiographic evidence of disease progression or rising PSA levels prior to day 1;
Subject may have 1 course of palliative radiation or surgical therapy to treat symptoms
resulting from metastatic disease if it was administered at least 4 weeks prior to day 1;
Up to 6 cycles of docetaxel therapy with final treatment administration completed within
2 months of day 1 and no evidence of disease progression during or after the completion of
docetaxel therapy;
Up to 6 months of ADT with LHRH agonists or antagonists or orchiectomy with or without
concurrent antiandrogens prior to day 1 if subject was treated with docetaxel, with no
radiographic evidence of disease progression or rising PSA levels prior to day 1;
Prior ADT given for < 39 months in duration and > 9 months before randomization as
neoadjuvant/adjuvant therapy.
2. Subject had a major surgery within 4 weeks prior to day 1.
3. Subject received treatment with 5-α reductase inhibitors (finasteride, dutasteride) within 4 weeks
prior to day 1.
4. Subject received treatment with estrogens, cyprotoerone acetate or androgens within 4 weeks
prior to day 1.
5. Subject received treatment with systemic glucocorticoids greater than the equivalent of 10 mg
per day of prednisone within 4 weeks prior to day 1.
6. Subject received treatment with herbal medications that have known hormonal antiprostate
cancer activity and/or are known to decrease PSA levels within 4 weeks prior to day 1.
7. Subject received prior aminoglutethimide, ketoconazole, abiraterone acetate or enzalutamide for
the treatment of prostate cancer or participation in a clinical study of an investigational agent that
inhibits the androgen receptor or androgen synthesis (e.g., TAK-700, ARN-509, ODM-201).
8. Subject received investigational agent within 4 weeks prior to day 1.
9. Subject has known or suspected brain metastasis or active leptomeningeal disease.
10. Subject has a history of another invasive cancer within 3 years of screening, with the exception
of fully treated cancers with a remote probability of recurrence based on Investigator assessment.
11. Subject has absolute neutrophil count < 1500/μL, platelet count < 100000/μL or hemoglobin
< 10 g/dL (6.2 mmol/L) at screening. NOTE: May not have received any growth factors within
7 days or blood transfusions within 28 days prior to the hematology values obtained at screening.
12. Subject has total bilirubin ≥ 1.5 x the upper limit of normal (except subjects with documented
Gilbert’s disease), or alanine aminotransferase or aspartate aminotransferase ≥ 2.5 x the upper
limit of normal at screening.
13. Subject has creatinine > 2 mg/dL (177 μmol/L) at screening.
14. Subject has albumin < 3.0 g/dL (30 g/L) at screening.
15. Subject has a history of seizure or any condition that may predispose to seizure (e.g., prior
cortical stroke or significant brain trauma, brain arteriovenous malformation).
16. Subject has history of loss of consciousness or transient ischemic attack within 12 months prior
to day 1.
17. Subject has clinically significant cardiovascular disease, including the following:
Myocardial infarction within 6 months prior to screening;
Unstable angina within 3 months prior to screening;
New York Heart Association class III or IV congestive heart failure or a history of New
York Heart Association class III or IV congestive heart failure unless a screening
echocardiogram or multigated acquisition scan performed within 3 months before the
randomization date demonstrates a left ventricular ejection fraction ≥ 45%;
History of clinically significant ventricular arrhythmias (e.g., sustained ventricular
tachycardia, ventricular fibrillation, torsades de pointes);
History of Mobitz II second-degree or third-degree heart block without a permanent
pacemaker in place;
Hypotension as indicated by systolic blood pressure < 86 mm Hg at screening;
Bradycardia as indicated by a heart rate of ≤ 45 beats per minute on the screening ECG;
Uncontrolled hypertension as indicated by a minimum of 2 consecutive blood pressure
measurements showing systolic blood pressure > 170 mm Hg or diastolic blood pressure
> 105 mm Hg at screening.
18. Subject has gastrointestinal disorder affecting absorption.
19. Subject has any concurrent disease, infection or comorbid condition that interferes with the
ability of the subject to participate in the study, which places the subject at undue risk or
complicates the interpretation of data in the opinion of the Investigator.
20. Subject received bisphosphonates or denosumab within 2 weeks prior to day 1 unless
administered at stable dose or to treat diagnosed osteoporosis.
21. Subject has shown a hypersensitivity reaction to the active pharmaceutical ingredient or any of
the study capsule components, including Labrasol®, butylated hydroxyanisole (BHA), and
butylated hydroxytoluene (BHT).
Waivers to the exclusion criteria will NOT be allowed.
Subject will be excluded from participation if any of the following apply:
1. Subject has received any prior pharmacotherapy, radiation therapy or surgery for metastatic
prostate cancer (the following exceptions are permitted):
Up to 3 months of ADT with luteinizing hormone-releasing hormone (LHRH) agonists or
antagonists or orchiectomy with or without concurrent antiandrogens prior to day 1, with no
radiographic evidence of disease progression or rising PSA levels prior to day 1;
Subject may have 1 course of palliative radiation or surgical therapy to treat symptoms
resulting from metastatic disease if it was administered at least 4 weeks prior to day 1;
Up to 6 cycles of docetaxel therapy with final treatment administration completed within
2 months of day 1 and no evidence of disease progression during or after the completion of
docetaxel therapy;
Up to 6 months of ADT with LHRH agonists or antagonists or orchiectomy with or without
concurrent antiandrogens prior to day 1 if subject was treated with docetaxel, with no
radiographic evidence of disease progression or rising PSA levels prior to day 1;
Prior ADT given for < 39 months in duration and > 9 months before randomization as
neoadjuvant/adjuvant therapy.
2. Subject had a major surgery within 4 weeks prior to day 1.
3. Subject received treatment with 5-α reductase inhibitors (finasteride, dutasteride) within 4 weeks
prior to day 1.
4. Subject received treatment with estrogens, cyprotoerone acetate or androgens within 4 weeks
prior to day 1.
5. Subject received treatment with systemic glucocorticoids greater than the equivalent of 10 mg
per day of prednisone within 4 weeks prior to day 1.
6. Subject received treatment with herbal medications that have known hormonal antiprostate
cancer activity and/or are known to decrease PSA levels within 4 weeks prior to day 1.
7. Subject received prior aminoglutethimide, ketoconazole, abiraterone acetate or enzalutamide for
the treatment of prostate cancer or participation in a clinical study of an investigational agent that
inhibits the androgen receptor or androgen synthesis (e.g., TAK-700, ARN-509, ODM-201).
8. Subject received investigational agent within 4 weeks prior to day 1.
9. Subject has known or suspected brain metastasis or active leptomeningeal disease.
10. Subject has a history of another invasive cancer within 3 years of screening, with the exception
of fully treated cancers with a remote probability of recurrence based on Investigator assessment.
11. Subject has absolute neutrophil count < 1500/μL, platelet count < 100000/μL or hemoglobin
< 10 g/dL (6.2 mmol/L) at screening. NOTE: May not have received any growth factors within
7 days or blood transfusions within 28 days prior to the hematology values obtained at screening.
12. Subject has total bilirubin ≥ 1.5 x the upper limit of normal (except subjects with documented
Gilbert’s disease), or alanine aminotransferase or aspartate aminotransferase ≥ 2.5 x the upper
limit of normal at screening.
13. Subject has creatinine > 2 mg/dL (177 μmol/L) at screening.
14. Subject has albumin < 3.0 g/dL (30 g/L) at screening.
15. Subject has a history of seizure or any condition that may predispose to seizure (e.g., prior
cortical stroke or significant brain trauma, brain arteriovenous malformation).
16. Subject has history of loss of consciousness or transient ischemic attack within 12 months prior
to day 1.
17. Subject has clinically significant cardiovascular disease, including the following:
Myocardial infarction within 6 months prior to screening;
Unstable angina within 3 months prior to screening;
New York Heart Association class III or IV congestive heart failure or a history of New
York Heart Association class III or IV congestive heart failure unless a screening
echocardiogram or multigated acquisition scan performed within 3 months before the
randomization date demonstrates a left ventricular ejection fraction ≥ 45%;
History of clinically significant ventricular arrhythmias (e.g., sustained ventricular
tachycardia, ventricular fibrillation, torsades de pointes);
History of Mobitz II second-degree or third-degree heart block without a permanent
pacemaker in place;
Hypotension as indicated by systolic blood pressure < 86 mm Hg at screening;
Bradycardia as indicated by a heart rate of ≤ 45 beats per minute on the screening ECG;
Uncontrolled hypertension as indicated by a minimum of 2 consecutive blood pressure
measurements showing systolic blood pressure > 170 mm Hg or diastolic blood pressure
> 105 mm Hg at screening.
18. Subject has gastrointestinal disorder affecting absorption.
19. Subject has any concurrent disease, infection or comorbid condition that interferes with the
ability of the subject to participate in the study, which places the subject at undue risk or
complicates the interpretation of data in the opinion of the Investigator.
20. Subject received bisphosphonates or denosumab within 2 weeks prior to day 1 unless
administered at stable dose or to treat diagnosed osteoporosis.
21. Subject has shown a hypersensitivity reaction to the active pharmaceutical ingredient or any of
the study capsule components, including Labrasol®, butylated hydroxyanisole (BHA), and
butylated hydroxytoluene (BHT).
Waivers to the exclusion criteria will NOT be allowed.
The Estimated Number of Participants
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Taiwan
50 participants
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Global
1100 participants
