An Asian Study to Evaluate Efficacy and Safety of Oral Enzalutamide in Progressive Metastatic Prostate Cancer Participants

Asian Multinational Phase 3, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of Oral Enzalutamide in Chemotherapy Naïve Subjects With Progressive Metastatic Prostate Cancer Who Have Failed Androgen Deprivation Therapy

Purpose of the study was to assess the effect of enzalutamide on time to Prostate Specific Antigen (PSA) progression as compared to placebo in chemotherapy naïve participants with progressive metastatic prostate cancer who have failed androgen deprivation therapy.

Study Overview

• Status: Completed
• Conditions: Progressive Metastatic Prostate Cancer
• Intervention / Treatment: Drug: Placebo; Drug: Enzalutamide

Detailed Description

The study was a multinational Phase 3, randomized, double-blind, placebo-controlled efficacy and safety study of oral enzalutamide (formerly MDV3100) in asymptomatic or mildly symptomatic participants with progressive metastatic prostate cancer who have disease progression despite androgen deprivation therapy. In order to join the study, participants could not have been previously treated with cytotoxic chemotherapy. Approximately 30 Chinese participants were allocated to the pharmacokinetic (PK) cohort. Participants in the PK cohort were required to be hospitalized from Day 1 before the randomization date to at least the completion of all the assessments planned on Day 3. All participants in the PK cohort underwent blood sampling for the PK analysis. Data reported in the results section was based on data cutoff dates of 20 Sept 2015 for efficacy and safety data and 20 Jan 2016 for PK outcome measures. The study completed double-blind period and is now in the open-label period.

• Study Type: Interventional
• Enrollment (Actual): 395
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • CN00103
  • Beijing, China
    • CN00104
  • Beijing, China
    • CN00106
  • Beijing, China
    • CN00111
  • Beijing, China
    • CN00112
  • Beijing, China
    • CN00114
  • Beijing, China
    • CN00115
  • Beijing, China
    • CN00127
  • Changsha, China
    • CN00121
  • Hangzhou, China
    • CN00107
  • Nanjing, China
    • CN00110
  • Nanjing, China
    • CN00117
  • Shanghai, China
    • CN00102
  • Shanghai, China
    • CN00105
  • Shanghai, China
    • CN00108
  • Shanghai, China
    • CN00113
  • Shanghai, China
    • CN00126
  • Suzhou, China
    • CN00119
  • Tianjin, China
    • CN00125
  • Wenzhou, China
    • CN00118
  • Wuhan, China
    • CN00109
  • Xi'an, China
    • CN00124
• Hong Kong
  • Hong Kong, Hong Kong
    • HK00402
• South Korea
  • Anyang, South Korea
    • KR00214
  • Busan, South Korea
    • KR00205
  • Busan, South Korea
    • KR00207
  • Cheongju-si, South Korea
    • KR00212
  • Daegu, South Korea
    • KR00203
  • Daejeon, South Korea
    • KR00213
  • Incheon, South Korea
    • KR00201
  • Seongnam-si, South Korea
    • KR00202
  • Seoul, South Korea
    • KR00204
  • Seoul, South Korea
    • KR00206
  • Seoul, South Korea
    • KR00208
  • Seoul, South Korea
    • KR00209
  • Seoul, South Korea
    • KR00210
  • Seoul, South Korea
    • KR00211
  • Seoul, South Korea
    • KR00215
• Taiwan
  • Kaohsiung City, Taiwan
    • TW00309
  • Taichung, Taiwan
    • TW00302
  • Taichung, Taiwan
    • TW00303
  • Tainan City, Taiwan
    • TW00307
  • Tainan City, Taiwan
    • TW00308
  • Taipei, Taiwan
    • TW00301
  • Taipei, Taiwan
    • TW00304
  • Taipei, Taiwan
    • TW00306
  • Taoyuan, Taiwan
    • TW00305

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
• Ongoing androgen deprivation therapy with a GnRH analogue or bilateral orchiectomy
• Progressive disease despite androgen deprivation therapy as defined by rising PSA levels or progressive soft tissue or bone disease
• No prior treatment with cytotoxic chemotherapy
• Asymptomatic or mildly symptomatic from prostate cancer

Exclusion Criteria:

• Severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the patient inappropriate for enrollment
• Known or suspected brain metastasis or active leptomeningeal disease
• History of another malignancy within the previous 5 years other than curatively treated non-melanomatous skin cancer
• History of seizure including febrile seizure or any condition that may predispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Enzalutamide; Participants received 160 mg of enzalutamide orally once a day during double blind period until Prostate-Specific Antigen (PSA) progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer. Eligible participants who received enzalutamide during double blind and who provided consent to take part in open-label period continued to receive 160 mg of enzalutamide in open-label period orally once a day until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer.	Drug: Enzalutamide; Oral; Other Names: Xtandi; MDV3100
Experimental: Placebo; Participants received enzalutamide matching placebo orally once a day during double-blind period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer.	Drug: Placebo; Oral
Experimental: Placebo followed by Enzalutamide; Eligible participants who received enzalutamide matching placebo during double-blind period and who provided consent to take part in open-label period, received 160 mg of enzalutamide orally once a day during open-label period until PSA progression and radiographic disease progression were centrally confirmed and 1 of the following 2 events became applicable to the participants: (1) initiation of cytotoxic chemotherapy or (2) initiation of an investigational agent for treatment of prostate cancer.	Drug: Enzalutamide; Oral; Other Names: Xtandi; MDV3100

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Prostate-specific Antigen (PSA) Progression	The time to Prostate Specific Antigen (PSA) progression was defined as the time from randomization to the PSA progression. The PSA progression was defined according to the consensus guidelines of Prostate Cancer Clinical Trials Working Group 2 (PCWG2).For participants with PSA decline at Week 13, the PSA progression date was defined as a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir, which would be confirmed by a second consecutive value obtained 3 or more weeks later. For participants with no PSA decline at Week 13, the PSA progression date was defined as the date when a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the baseline was documented, which was confirmed by a second consecutive value 3 or more weeks later. Time to PSA progression was estimated using the Kaplan-Meier method. Participants without confirmed PSA progression were censored.	From the date of randomization to PSA progression median follow-up time is 6.47 months for enzalutamide and 2.99 months for placebo

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Overall Survival	Duration of overall survival was defined as the time from the randomization to deaths from any cause. For participants who were alive at the time of the data analysis, overall survival time was censored to the last know date the participants were known to be alive.	From the date of randomization to deaths from any cause median follow-up time is 42.32 months for enzalutamide and 26.81 months for placebo
Duration of Radiographic Progression-free Survival (rPFS) Based on Independent Central Review Facility Assessment	Duration of Radiographic Progression-free Survival (rPFS) was defined as the time from randomization to the rPFS event (deaths from any cause and radiographic disease progression). Radiographic disease progression is defined by RECIST 1.1 for soft tissue disease, or PCWG2 for bone lesions. If a participant met the criteria for more than 1 censoring rule, they were censored with the earliest censoring date. The radiographic progression date was the first date when progression definition was met, not confirmed.	From the date of randomization to the rPFS event (deaths from any cause and radiographic disease progression) median follow-up time is 5.55 months for enzalutamide and 3.71 months for placebo
Time to First Skeletal-Related Event	Time to first skeletal-related event (SRE) was defined as the time from randomization to the first skeletal-related event, defined as radiation therapy or surgery to bone, pathologic bone fracture, spinal cord compression, or change of anti-neoplastic therapy to treat bone pain. Participants who have not had a SRE at the time of the analysis were censored at their last assessment indicating no evidence of SRE.	From the date of randomization to the first skeletal-related event median follow-up time is 7.39 months for enzalutamide and 5.29 months for placebo
Time to Initiation of Cytotoxic Chemotherapy	Time to initiation of cytotoxic chemotherapy was defined as the time from randomization to initiation of cytotoxic chemotherapy. It included only therapies for prostate cancer. When multiple cytotoxic chemotherapies were initiated, the first chemotherapy was used to determine the time to event. Participants who did not start cytotoxic chemotherapy at the time of analysis data cutoff were censored at the date of their last assessment indicating no evidence of cytotoxic chemotherapy usage.	From the date of randomization to initiation of cytotoxic chemotherapy median follow-up time is 7.39 months for enzalutamide and 5.19 months for placebo
Number of Participants With Confirmed Best PSA Response (≥50% Decrease From Baseline)	Best PSA response was defined as as ≥50% reductions in PSA level from baseline to the lowest post-baseline PSA result as determined by the central laboratory, with a consecutive assessment conducted at least 3 weeks later to confirm the PSA response. Only participants who had both baseline and post-baseline assessments were included in the analysis.	From baseline to the lowest post-baseline PSA result median treatment duration is 6.60 months for enzalutamide and 3.70 months for placebo
Best Overall Soft Tissue Response	Participants with measurable soft tissue disease at screening visit (i.e., at least one target lesion per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) who have an objective response (complete response (CR) or partial response (PR)) during the study were included in the best overall soft tissue response assessment. The best overall soft tissue response was based on the investigator assessment using RECIST 1.1. CR was defined as complete resolution of all attributable clinical symptoms and physical findings. PR was defined as partial resolution of at Least some of the clinical symptoms and physical findings.	From the date of randomization median treatment duration is 6.60 months for enzalutamide and 3.70 months for placebo
Time to Maximum Concentration (Tmax) of Enzalutamide, M1,M2 and Enzalutamide Plus M2		From the date of randomization, Single Dosing Day 1 and Multiple Dosing Day 85
Maximum Observed Plasma Concentration During the First 24 Hours After Dosing (Cmax) Enzalutamide, M1,M2 and Enzalutamide Plus M2		From the date of randomization, Single Dosing Day 1 and Multiple Dosing Day 85
AUC From the Time of Dosing to 24 h After Dosing (AUC24h) Enzalutamide, M1,M2 and Enzalutamide Plus M2		From the date of randomization, Single Dosing Day 1 and Multiple Dosing Day 85
Concentration 24 h After Dosing (C24h) Enzalutamide, M1,M2 and Enzalutamide Plus M2	N is the number of participants with available data at this time point.	From the date of randomization, Single Dosing Day 1 and Multiple Dosing Day 85
Observed Plasma Concentration in Predose Samples Obtained During Multiple-dose Administration of Minimum Concentration (Plasma Concentration at Pre Dose) (Cmin) Enzalutamide, M1,M2 and Enzalutamide Plus M2	N is the number of participants with available data at this time point.	From the date of randomization up to Days 2, 3, 8, 22, 29, 43, 57, 85, 86, 113, 141 and 169
Apparent Total Systemic Clearance After Multiple Dosing (CL/F) Enzalutamide, M1,M2 and Enzalutamide Plus M2 (For Unchanged Enzalutamide Only)		From the date of randomization up to Multiple Dosing Day 85
Peak-Trough Ratio (PTR) Enzalutamide, M1,M2 and Enzalutamide Plus M2		From the date of randomization up to Multiple Dosing Day 85
AUC From the Time of Dosing to the Start of the Next Dosing Interval (AUCtau) Enzalutamide, M1,M2 and Enzalutamide Plus M2		From the date of randomization up to Multiple Dosing Day 85
Number of Participants With Adverse Events (AE)	An AE was defined as any untoward medical occurrence, temporally associated with use of medicinal product, whether considered related to medicinal product. AE could therefore be any unfavorable & unintended sign, symptom, or disease temporally associated with use of a medicinal product. An AE was considered serious if, results in death; is life-threatening; results in persistent disability; results in congenital anomaly; requires inpatient hospitalization; or leads to prolongation of hospitalization; other medically important events. TEAE was defined as AE occurring from time of study drug administration on Day 1 until follow-up visit (28 days after last dose, or one day before date of initiation of cytotoxic chemotherapy or an investigational agent, whichever comes first). AEs were graded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening; Grade 5 = Fatal.	From first dose on Day 1 until 28 days after the last dose of study drug, or one day before the date of initiation of cytotoxic chemotherapy or an investigational agent for treatment of prostate cancer, whichever comes first, up to 123 months and 24 days

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc
• Investigators: Study Director: Central Contact, Astellas Pharma Inc

Publications and helpful links

General Publications

• Pu YS, Ahn H, Han W, Huang SP, Wu HC, Ma L, Yamada S, Suga K, Xie LP. Enzalutamide in Chemotherapy-Naive Metastatic Castration-Resistant Prostate Cancer: An Asian Multiregional, Randomized Study. Adv Ther. 2022 Jun;39(6):2641-2656. doi: 10.1007/s12325-022-02140-2. Epub 2022 Apr 10.

Helpful Links

• Link to results and other applicable study documents on the Astellas Clinical Trials website.
• Link to plain language summary of the study on the Trial Results Summaries website.

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2014
• Primary Completion (Actual): September 20, 2015
• Study Completion (Actual): July 17, 2024

Study Registration Dates

• First Submitted: November 13, 2014
• First Submitted That Met QC Criteria: November 17, 2014
• First Posted (Estimated): November 19, 2014

Study Record Updates

• Last Update Posted (Estimated): October 24, 2025
• Last Update Submitted That Met QC Criteria: October 22, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Prostate cancer; Xtandi; Enzalutamide; Androgen receptor
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Central Nervous System Diseases; Nervous System Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Genetic Diseases, X-Linked; Spinal Cord Diseases; Motor Neuron Disease; Muscular Atrophy, Spinal; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Prostatic Neoplasms; Bulbo-Spinal Atrophy, X-Linked; enzalutamide
• Other Study ID Numbers: 9785-CL-0232; CTR20140131 (Registry Identifier: ChinaDrugTrials.org.cn)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
• IPD Sharing Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• IPD Sharing Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes