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NCT02294461

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

Completed Phase 3 Results posted Last updated 24 October 2025
What this trial tests

Phase 3 trial testing Enzalutamide in Progressive Metastatic Prostate Cancer in 395 participants. Completed in 17 July 2024.

Timeline
23 April 2014
Primary endpoint
20 September 2015
17 July 2024

Quick facts

Lead sponsorAstellas Pharma Inc
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment395
Start date23 April 2014
Primary completion20 September 2015
Estimated completion17 July 2024
Sites47 locations across China, Hong Kong, Taiwan, South Korea

Drugs / interventions tested

Conditions studied

Sponsor

Astellas Pharma Inc — full company profile →

Who can join

18 and older, male only, with Progressive Metastatic Prostate Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Time to Prostate-specific Antigen (PSA) Progression Primary · From the date of randomization to PSA progression median follow-up time is 6.47 months for enzalutamide and 2.99 months for placebo

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

GroupValue95% CI
Enzalutamide8.315.72 – 10.25
Placebo2.862.83 – 4.63
Duration of Overall Survival Secondary · 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 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.

GroupValue95% CI
Enzalutamide39.0629.24 – 57.63
Placebo27.1021.88 – 37.82
Duration of Radiographic Progression-free Survival (rPFS) Based on Independent Central Review Facility Assessment Secondary · 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

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.

GroupValue95% CI
EnzalutamideNA10.97 – NA
Placebo5.293.61 – 11.33
Time to First Skeletal-Related Event Secondary · 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 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.

GroupValue95% CI
EnzalutamideNANA – NA
PlaceboNANA – NA
Time to Initiation of Cytotoxic Chemotherapy Secondary · 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

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.

GroupValue95% CI
EnzalutamideNANA – NA
Placebo13.93NA – NA
Number of Participants With Confirmed Best PSA Response (≥50% Decrease From Baseline) Secondary · 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 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.

GroupValue95% CI
Enzalutamide120
Placebo15
Best Overall Soft Tissue Response Secondary · From the date of randomization median treatment duration is 6.60 months for enzalutamide and 3.70 months for placebo

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 c

GroupValue95% CI
Enzalutamide18
Placebo1
Time to Maximum Concentration (Tmax) of Enzalutamide, M1,M2 and Enzalutamide Plus M2 Secondary · From the date of randomization, Single Dosing Day 1 and Multiple Dosing Day 85
Day 1
GroupValue95% CI
Enzalutamide0.9750.500 – 6.05
M1- Carboxylic Acid Metabolite24.00.550 – 24.9
M2- N-Desmethyl Enzalutamide24.00.550 – 24.9
Enzalutamide Plus M20.9750.500 – 24.0
Day 85
GroupValue95% CI
Enzalutamide1.000 – 2.00
M1- Carboxylic Acid Metabolite1.020.217 – 24.1
M2- N-Desmethyl Enzalutamide00 – 23.8
Enzalutamide Plus M20.2500 – 23.8
Maximum Observed Plasma Concentration During the First 24 Hours After Dosing (Cmax) Enzalutamide, M1,M2 and Enzalutamide Plus M2 Secondary · From the date of randomization, Single Dosing Day 1 and Multiple Dosing Day 85
Day 1
GroupValue95% CI
Enzalutamide3.92± 1.37
M1- Carboxylic Acid Metabolite0.112± 0.0794
M2- N-Desmethyl Enzalutamide0.175± 0.0921
Enzalutamide Plus M23.94± 1.34
Day 85
GroupValue95% CI
Enzalutamide20.0± 3.22
M1- Carboxylic Acid Metabolite14.0± 23.5
M2- N-Desmethyl Enzalutamide15.2± 3.44
Enzalutamide Plus M234.2± 4.98
AUC From the Time of Dosing to 24 h After Dosing (AUC24h) Enzalutamide, M1,M2 and Enzalutamide Plus M2 Secondary · From the date of randomization, Single Dosing Day 1 and Multiple Dosing Day 85
GroupValue95% CI
Enzalutamide43.1± 9.64
M1- Carboxylic Acid Metabolite1.81± 0.972
M2- N-Desmethyl Enzalutamide2.17± 1.30
Enzalutamide Plus M245.3± 10.1
Concentration 24 h After Dosing (C24h) Enzalutamide, M1,M2 and Enzalutamide Plus M2 Secondary · From the date of randomization, Single Dosing Day 1 and Multiple Dosing Day 85

N is the number of participants with available data at this time point.

Day 1
GroupValue95% CI
Enzalutamide1.65± 0.343
M1- Carboxylic Acid Metabolite0.111± 0.0801
M2- N-Desmethyl Enzalutamide0.164± 0.0942
Enzalutamide Plus M21.82± 0.363
Day 85
GroupValue95% CI
Enzalutamide17.6± 3.09
M1- Carboxylic Acid Metabolite6.09± 3.07
M2- N-Desmethyl Enzalutamide13.7± 2.91
Enzalutamide Plus M231.2± 4.00
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 Secondary · From the date of randomization up to Days 2, 3, 8, 22, 29, 43, 57, 85, 86, 113, 141 and 169

N is the number of participants with available data at this time point.

Day 2 predose
GroupValue95% CI
Enzalutamide1.65± 0.343
M1- Carboxylic Acid Metabolite0.111± 0.0801
M2- N-Desmethyl Enzalutamide0.164± 0.0942
Enzalutamide Plus M21.82± 0.363
Day 3 predose
GroupValue95% CI
Enzalutamide3.29± 1.16
M1- Carboxylic Acid Metabolite0.302± 0.256
M2- N-Desmethyl Enzalutamide0.367± 0.188
Enzalutamide Plus M23.66± 1.24
Day 8 predose
GroupValue95% CI
Enzalutamide9.39± 2.07
M1- Carboxylic Acid Metabolite1.21± 0.923
M2- N-Desmethyl Enzalutamide1.94± 0.983
Enzalutamide Plus M211.3± 2.62
Day 22 predose
GroupValue95% CI
Enzalutamide17.6± 2.37
M1- Carboxylic Acid Metabolite6.09± 8.26
M2- N-Desmethyl Enzalutamide8.34± 2.74
Enzalutamide Plus M225.9± 3.25
Day 29 predose
GroupValue95% CI
Enzalutamide19.6± 4.00
M1- Carboxylic Acid Metabolite8.16± 12.5
M2- N-Desmethyl Enzalutamide10.9± 3.72
Enzalutamide Plus M230.5± 5.47
Day 43 predose
GroupValue95% CI
Enzalutamide17.0± 4.13
M1- Carboxylic Acid Metabolite12.5± 22.1
M2- N-Desmethyl Enzalutamide14.0± 3.99
Enzalutamide Plus M231.0± 5.82
Day 57 predose
GroupValue95% CI
Enzalutamide17.8± 3.09
M1- Carboxylic Acid Metabolite18.4± 28.2
M2- N-Desmethyl Enzalutamide14.7± 3.88
Enzalutamide Plus M232.5± 4.57
Day 85 predose
GroupValue95% CI
Enzalutamide17.9± 3.19
M1- Carboxylic Acid Metabolite6.33± 2.95
M2- N-Desmethyl Enzalutamide14.9± 3.67
Enzalutamide Plus M232.8± 5.10

Adverse events — posted to ClinicalTrials.gov

Time frame: All cause mortality: From the date of randomization up to 123 months and 24 days AE: 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. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Enzalutamide
Serious: 87/202 (43%)
Deaths: 85/202
Placebo
Serious: 57/193 (30%)
Deaths: 57/193
Placebo Patients Crossover to Enzalutamide 160 mg
Serious: 24/51 (47%)
Deaths: 21/51

Serious adverse events (175 terms)

ReactionSystemEnzalutamidePlaceboPlacebo Patients Crossover…
PneumoniaInfections and infestations
HaematuriaRenal and urinary disorders
Urinary retentionRenal and urinary disorders
Cardiac failureCardiac disorders
AnaemiaBlood and lymphatic system disorders
Bone painMusculoskeletal and connective tissue disorders
Acute kidney injuryRenal and urinary disorders
ChemotherapySurgical and medical procedures
Upper gastrointestinal haemorrhageGastrointestinal disorders
AstheniaGeneral disorders
DeathGeneral disorders
Decreased appetiteMetabolism and nutrition disorders
Prostate cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
DizzinessNervous system disorders
HydronephrosisRenal and urinary disorders
HypertensionVascular disorders
Cardiopulmonary failureCardiac disorders
CataractEye disorders
Gastrointestinal haemorrhageGastrointestinal disorders
Intestinal obstructionGastrointestinal disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
Septic shockInfections and infestations
Upper respiratory tract infectionInfections and infestations
ContusionInjury, poisoning and procedural complications
Other adverse events (28 terms — click to expand)

ReactionSystemEnzalutamidePlaceboPlacebo Patients Crossover…
Decreased appetiteMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
AnaemiaBlood and lymphatic system disorders
FatigueGeneral disorders
ConstipationGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Bone painMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
NauseaGastrointestinal disorders
Weight decreasedInvestigations
NasopharyngitisInfections and infestations
DizzinessNervous system disorders
HypertensionVascular disorders
InsomniaPsychiatric disorders
DysuriaRenal and urinary disorders
Oedema peripheralGeneral disorders
Musculoskeletal painMusculoskeletal and connective tissue disorders
PollakiuriaRenal and urinary disorders
Upper respiratory tract infectionInfections and infestations
PyrexiaGeneral disorders
HaematuriaRenal and urinary disorders
VomitingGastrointestinal disorders
AstheniaGeneral disorders
CoughRespiratory, thoracic and mediastinal disorders
DiarrhoeaGastrointestinal disorders
HypokalaemiaMetabolism and nutrition disorders
PeriodontitisInfections and infestations
HypoalbuminaemiaMetabolism and nutrition disorders

Most-reported serious reactions: Pneumonia, Haematuria, Urinary retention, Cardiac failure, Anaemia, Bone pain, Acute kidney injury, Chemotherapy.

Data from ClinicalTrials.gov NCT02294461 adverse events section.

Sponsor's own description

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.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Enzalutamide in Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer: An Asian Multiregional, Randomized Study.
    Pu YS, Ahn H, Han W, Huang SP, et al · · 2022 · cited 19× · PMID 35397772 · DOI 10.1007/s12325-022-02140-2
  2. Cardiovascular events among men with prostate cancer treated with androgen receptor signaling inhibitors: a systematic review, meta-analysis, and network meta-analysis.
    Matsukawa A, Yanagisawa T, Parizi MK, Laukhtina E, et al · · 2025 · cited 9× · PMID 39237679 · DOI 10.1038/s41391-024-00886-0
  3. Correlation Between Imaging-Based Intermediate Endpoints and Overall Survival in Men With Metastatic Castration-Resistant Prostate Cancer: Analysis of 28 Randomized Trials Using the Prostate Cancer Clinical Trials Working Group (PCWG2) Criteria in 16,511 Patients.
    Woo S, Suh CH, Wibmer AG, Becker AS, et al · · 2022 · cited 9× · PMID 34903480 · DOI 10.1016/j.clgc.2021.11.007
  4. Comparative efficacy and safety of talazoparib plus enzalutamide and other first-line treatments for metastatic castration-resistant prostate cancer.
    Castro E, Ellis J, Craigie S, Haltner A, et al · · 2025 · cited 4× · PMID 39427229 · DOI 10.1093/oncolo/oyae237
  5. Evaluating first-line therapeutic strategies for metastatic castration-resistant prostate cancer: a comprehensive network meta-analysis and systematic review.
    Zhang D, Weng H, Zhu Z, Gong W, et al · · 2024 · cited 4× · PMID 38686197 · DOI 10.3389/fonc.2024.1378993
  6. Radiographic progression-free survival as a surrogate endpoint for overall survival in first-line ARPi naïve metastatic castration-resistant prostate cancer.
    Castro E, Paganelli S, Wang D, Haltner A, et al · · 2026 · PMID 41495009 · DOI 10.1093/oncolo/oyaf425

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