Clinical Trials List
Protocol NumberMDV3100-13
NCT Number(ClinicalTrials.gov Identfier)NCT02319837
2015-11-01 - 2026-12-31
Phase III
Terminated7
ICD-10C61
Malignant neoplasm of prostate
A Phase 3, Randomized, Efficacy and Safety Study of Enzalutamide Plus Leuprolide, Enzalutamide Monotherapy, and Placebo Plus Leuprolide in Men With High-Risk Nonmetastatic Prostate Cancer Progressing After Definitive Therapy
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Trial Applicant
IQVIA RDS Taiwan Ltd.
-
Sponsor
Medivation, 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
- Shian-Shiang Wang Division of Urology
- 蔡世傳 Division of Nuclear Medicine
- Cheng-Kuang Yang Division of Urology
- 林萬鈺 Division of Nuclear Medicine
- 裘坤元 Division of Urology
- 熊小澐 Division of Radiology
- 歐宴泉 Division of Urology
- Chuan-Shu Chen Division of Urology
- Jian-Ri Li Division of Urology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Chao-Hsiang Chang Division of Urology
- 陳冠亨 Division of Urology
- Yi-Huei Chang Division of Urology
- Chi-Ping Huang Division of Urology
- Po-Fan Hsieh Division of Urology
- Wen-Chi Chen Division of Urology
- Chi-Rei Yang Division of Urology
- Chi-Shun Lien Division of Urology
- Chin-Chung Yeh Division of Urology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
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 Stop recruiting
Co-Principal Investigator
Audit
None
Linkou Chang Gung Medical Foundation
Taiwan National PI
林永昌
Co-Principal Investigator
- Rita cheng Division of Hematology & Oncology
- 范綱行 Division of Radiation Therapy
- 張英勛 Division of Hematology & Oncology
- See-Tong Pang Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
1 Stop recruiting
Audit
None
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- CHUNG-HSIN CHEN Division of Urology
- YEN-HENG LIN Division of Radiology
- 劉詩彬 Division of Urology
- - - Division of Urology
- Hong-Chiang Chang Division of Urology
- 戴槐青 Division of Urology
- CHING-CHU LU Division of Nuclear Medicine
- - - Division of Urology
- Chia-Hsien Chen Division of Radiology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
- Yi-Hsiu Huang Division of Urology
- 沈書慧 Division of Radiology
- Tzu-Ping Lin Division of Urology
- Hsiao-Jen Chung Division of Urology
- 朱力行 Division of Nuclear Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Prostate Cancer
Objectives
Primary:
To evaluate efficacy, as measured by metastasis-free survival (MFS)
Secondary:
To evaluate efficacy, as measured by the following:
– Key protected secondary endpoints:
Overall survival
Proportion of patients per group who remain treatment-free 2 years after suspension of study drug
treatment at week 37 due to undetectable prostate-specific antigen (PSA)
Time to castration resistance
– Proportion of patients per group with undetectable PSA 2 years after suspension of study drug
treatment at week 37 due to undetectable PSA
– Proportion of patients per group with undetectable PSA at 36 weeks on study drug
– Prostate cancer-specific survival
– Time to resumption of any hormonal therapy following suspension at week 37 due to undetectable
PSA
– Time to first symptomatic skeletal event
– Time to metastasis
– Time to clinically relevant pain
– Quality of life
To evaluate safety
Test Drug
Enzalutamide (formerly MDV3100)
Active Ingredient
Enzalutamide
Dosage Form
liquid-filled soft gelatin capsule
Dosage
40
Endpoints
Primary Efficacy Endpoint:
The primary efficacy endpoint is MFS using independent, blinded central radiology reviewer assessment of
radiographic progression. MFS is defined as the duration of time in months between randomization and the
earliest objective evidence of radiographic progression by central imaging or death on study (death within
168 days after permanent treatment discontinuation), whichever occurs first.
The primary endpoint analysis will be performed when at least 480 MFS events occur in the 2 blinded treatment
groups tested in the first hypothesis (1), at which time at least 690 MFS events are expected to occur in the
3 treatment groups combined. A 2-sided stratified log-rank test will compare treatment groups at the 0.05 level
of significance.
The primary efficacy endpoint is MFS using independent, blinded central radiology reviewer assessment of
radiographic progression. MFS is defined as the duration of time in months between randomization and the
earliest objective evidence of radiographic progression by central imaging or death on study (death within
168 days after permanent treatment discontinuation), whichever occurs first.
The primary endpoint analysis will be performed when at least 480 MFS events occur in the 2 blinded treatment
groups tested in the first hypothesis (1), at which time at least 690 MFS events are expected to occur in the
3 treatment groups combined. A 2-sided stratified log-rank test will compare treatment groups at the 0.05 level
of significance.
Inclution Criteria
Inclusion Criteria
Each patient eligible to participate in this study must meet all of the following criteria:
1. Age 18 years or older and willing and able to provide informed consent.
2. Histologically or cytologically confirmed adenocarcinoma of the prostate at initial
biopsy, without neuroendocrine differentiation, signet cell, or small cell features.
3. Prostate cancer initially treated by radical prostatectomy or radiotherapy (including
brachytherapy) or both, with curative intent.
4. PSA doubling time ≤ 9 months as calculated by the sponsor.
5. Screening PSA ≥ 2.0 ng/mL for patients who had radical prostatectomy as primary
treatment for prostate cancer or ≥ 5.0 ng/mL and greater than or equal to the nadir
+ 2 ng/mL for patients who had radiotherapy as primary treatment for prostate cancer.
6. Serum testosterone ≥ 150 ng/dL (5.2 nmol/L) at screening.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening.
8. Estimated life expectancy of ≥ 12 months.
9. Able to swallow the study drug and comply with study requirements including
independently completing study questionnaires.
10. Throughout study, the patient 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 or per local guidelines where these require additional description of
contraceptive methods. Two acceptable methods of birth control thus include the
following:
Condom (barrier method is required)
AND
One of the following is required:
– Established and ongoing use of oral, injected, or implanted hormonal method of
contraception by the female partner
– Placement of an intrauterine device or intrauterine system by the female partner
– Additional barrier method including contraceptive sponge and occlusive cap
(diaphragm or cervical/vault caps) with spermicidal
foam/gel/film/cream/suppository by the female partner
– Tubal ligation in the female partner performed at least 6 months before screening
– Vasectomy or other procedure resulting in infertility (eg, bilateral orchiectomy),
performed at least 6 months before screening
11. Throughout the study, the patient must use a condom if having sex with a pregnant
woman.
12. Must agree not to donate sperm from first dose of study drug through 3 months after the
last dose of study drug.
Each patient eligible to participate in this study must meet all of the following criteria:
1. Age 18 years or older and willing and able to provide informed consent.
2. Histologically or cytologically confirmed adenocarcinoma of the prostate at initial
biopsy, without neuroendocrine differentiation, signet cell, or small cell features.
3. Prostate cancer initially treated by radical prostatectomy or radiotherapy (including
brachytherapy) or both, with curative intent.
4. PSA doubling time ≤ 9 months as calculated by the sponsor.
5. Screening PSA ≥ 2.0 ng/mL for patients who had radical prostatectomy as primary
treatment for prostate cancer or ≥ 5.0 ng/mL and greater than or equal to the nadir
+ 2 ng/mL for patients who had radiotherapy as primary treatment for prostate cancer.
6. Serum testosterone ≥ 150 ng/dL (5.2 nmol/L) at screening.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening.
8. Estimated life expectancy of ≥ 12 months.
9. Able to swallow the study drug and comply with study requirements including
independently completing study questionnaires.
10. Throughout study, the patient 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 or per local guidelines where these require additional description of
contraceptive methods. Two acceptable methods of birth control thus include the
following:
Condom (barrier method is required)
AND
One of the following is required:
– Established and ongoing use of oral, injected, or implanted hormonal method of
contraception by the female partner
– Placement of an intrauterine device or intrauterine system by the female partner
– Additional barrier method including contraceptive sponge and occlusive cap
(diaphragm or cervical/vault caps) with spermicidal
foam/gel/film/cream/suppository by the female partner
– Tubal ligation in the female partner performed at least 6 months before screening
– Vasectomy or other procedure resulting in infertility (eg, bilateral orchiectomy),
performed at least 6 months before screening
11. Throughout the study, the patient must use a condom if having sex with a pregnant
woman.
12. Must agree not to donate sperm from first dose of study drug through 3 months after the
last dose of study drug.
Exclusion Criteria
Exclusion Criteria
Each patient eligible to participate in this study must NOT meet any of the following
exclusion criteria:
1. Prior or present evidence of distant metastatic disease as assessed by computed
tomography (CT) or magnetic resonance imaging (MRI) or chest x-ray for soft tissue
disease and whole-body radionuclide bone scan for bone disease. Patients with soft
tissue pelvic disease may be eligible if lesions do not qualify as target lesions (eg, lymph
nodes below aortic bifurcation are permissible if the short axis of the largest lymph node
is < 15 mm). If the screening bone scan shows a lesion suggestive of metastatic disease,
the patient will be eligible only if a second imaging modality (plain film, CT, or MRI)
does not show bone metastasis. If the imaging results are equivocal or consistent with
metastasis, the patient is not eligible for enrollment.
2. Prior hormonal therapy other than neoadjuvant/adjuvant therapy to treat prostate cancer
≤ 36 months in duration and ≥ 9 months before randomization.
3. Prior cytotoxic chemotherapy, aminoglutethimide, ketoconazole, abiraterone acetate, or
enzalutamide for prostate cancer.
4. Prior systemic biologic therapy, including immunotherapy, for prostate cancer.
5. Major surgery within 4 weeks before randomization date.
6. Treatment with 5-α reductase inhibitors (finasteride, dutasteride) within 4 weeks of
randomization.
7. For patients who had a prior prostatectomy, a suitable candidate for salvage radiotherapy
as determined by the investigator in consideration of appropriate guidelines
(eg, American Society for Radiation Oncology / American Urological Association
[ASTRO/AUA]; European Association of Urology [EAU]).
8. Participation in a clinical study of an investigational agent that inhibits the androgen
receptor or androgen synthesis (eg, TAK-700, ARN-509, ODM-201); patients who
received placebo are allowed.
9. Use of any other investigational agent within 4 weeks before randomization date.
10. Known or suspected brain metastasis or active leptomeningeal disease.
11. History of another invasive cancer within 3 years before screening, with the exception of
fully treated cancers with a remote probability of recurrence. The medical monitor and
investigator must agree that the possibility of recurrence is remote.
12. Absolute neutrophil count < 1500/µL, platelet count < 100,000/µL, or hemoglobin
< 10 g/dL (6.2 mmol/L) at screening. NOTE: May not have received any growth factors
or blood transfusions within 7 days before the hematology values obtained at screening.
13. Total bilirubin ≥ 1.5-times the upper limit of normal (except patients with documented
Gilbert’s disease), or alanine aminotransferase (ALT) or aspartate aminotransferase
(AST) ≥ 2.5-times the upper limit of normal at screening.
14. Creatinine > 2 mg/dL (177 µmol/L) at screening.
15. Albumin < 3.0 g/dL (30 g/L) at screening.
16. History of seizure or any condition that may predispose to seizure (eg, prior cortical
stroke or significant brain trauma). History of loss of consciousness or transient ischemic
attack within 12 months before randomization.
17. Clinically significant cardiovascular disease including the following:
Myocardial infarction within 6 months before screening
Unstable angina within 3 months before 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 (eg, 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
electrocardiogram (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. Gastrointestinal disorder affecting absorption.
19. Hypersensitivity reaction to enzalutamide or any of the capsule components, including
Labrasol, butylated hydroxyanisole, and butylated hydroxytoluene.
20. Contraindication to the use of leuprolide, such as a previous hypersensitivity reaction to
an LHRH analogue or any of the excipients in the leuprolide injection.
21. Ongoing drug or alcohol abuse as per investigator judgment.
22. Any concurrent disease, infection, or comorbid condition that interferes with the ability
of the patient to participate in the study, which places the patient at undue risk, or
complicates the interpretation of data, in the opinion of the investigator or medical
monitor.
Each patient eligible to participate in this study must NOT meet any of the following
exclusion criteria:
1. Prior or present evidence of distant metastatic disease as assessed by computed
tomography (CT) or magnetic resonance imaging (MRI) or chest x-ray for soft tissue
disease and whole-body radionuclide bone scan for bone disease. Patients with soft
tissue pelvic disease may be eligible if lesions do not qualify as target lesions (eg, lymph
nodes below aortic bifurcation are permissible if the short axis of the largest lymph node
is < 15 mm). If the screening bone scan shows a lesion suggestive of metastatic disease,
the patient will be eligible only if a second imaging modality (plain film, CT, or MRI)
does not show bone metastasis. If the imaging results are equivocal or consistent with
metastasis, the patient is not eligible for enrollment.
2. Prior hormonal therapy other than neoadjuvant/adjuvant therapy to treat prostate cancer
≤ 36 months in duration and ≥ 9 months before randomization.
3. Prior cytotoxic chemotherapy, aminoglutethimide, ketoconazole, abiraterone acetate, or
enzalutamide for prostate cancer.
4. Prior systemic biologic therapy, including immunotherapy, for prostate cancer.
5. Major surgery within 4 weeks before randomization date.
6. Treatment with 5-α reductase inhibitors (finasteride, dutasteride) within 4 weeks of
randomization.
7. For patients who had a prior prostatectomy, a suitable candidate for salvage radiotherapy
as determined by the investigator in consideration of appropriate guidelines
(eg, American Society for Radiation Oncology / American Urological Association
[ASTRO/AUA]; European Association of Urology [EAU]).
8. Participation in a clinical study of an investigational agent that inhibits the androgen
receptor or androgen synthesis (eg, TAK-700, ARN-509, ODM-201); patients who
received placebo are allowed.
9. Use of any other investigational agent within 4 weeks before randomization date.
10. Known or suspected brain metastasis or active leptomeningeal disease.
11. History of another invasive cancer within 3 years before screening, with the exception of
fully treated cancers with a remote probability of recurrence. The medical monitor and
investigator must agree that the possibility of recurrence is remote.
12. Absolute neutrophil count < 1500/µL, platelet count < 100,000/µL, or hemoglobin
< 10 g/dL (6.2 mmol/L) at screening. NOTE: May not have received any growth factors
or blood transfusions within 7 days before the hematology values obtained at screening.
13. Total bilirubin ≥ 1.5-times the upper limit of normal (except patients with documented
Gilbert’s disease), or alanine aminotransferase (ALT) or aspartate aminotransferase
(AST) ≥ 2.5-times the upper limit of normal at screening.
14. Creatinine > 2 mg/dL (177 µmol/L) at screening.
15. Albumin < 3.0 g/dL (30 g/L) at screening.
16. History of seizure or any condition that may predispose to seizure (eg, prior cortical
stroke or significant brain trauma). History of loss of consciousness or transient ischemic
attack within 12 months before randomization.
17. Clinically significant cardiovascular disease including the following:
Myocardial infarction within 6 months before screening
Unstable angina within 3 months before 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 (eg, 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
electrocardiogram (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. Gastrointestinal disorder affecting absorption.
19. Hypersensitivity reaction to enzalutamide or any of the capsule components, including
Labrasol, butylated hydroxyanisole, and butylated hydroxytoluene.
20. Contraindication to the use of leuprolide, such as a previous hypersensitivity reaction to
an LHRH analogue or any of the excipients in the leuprolide injection.
21. Ongoing drug or alcohol abuse as per investigator judgment.
22. Any concurrent disease, infection, or comorbid condition that interferes with the ability
of the patient to participate in the study, which places the patient at undue risk, or
complicates the interpretation of data, in the opinion of the investigator or medical
monitor.
The Estimated Number of Participants
-
Taiwan
75 participants
-
Global
1860 participants
