NCT02294461 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2025-10-24

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Time to Prostate-specific Antigen (PSA) Progression

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outcome · POSTED

Duration of Overall Survival

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outcome · POSTED

Duration of Radiographic Progression-free Survival (rPFS) Based on Independent Central Review Facility Assessment

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outcome · POSTED

Time to First Skeletal-Related Event

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outcome · POSTED

Time to Initiation of Cytotoxic Chemotherapy

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outcome · POSTED

Number of Participants With Confirmed Best PSA Response (≥50% Decrease From Baseline)

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outcome · POSTED

Best Overall Soft Tissue Response

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outcome · POSTED

Time to Maximum Concentration (Tmax) of Enzalutamide, M1,M2 and Enzalutamide Plus M2

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outcome · POSTED

Maximum Observed Plasma Concentration During the First 24 Hours After Dosing (Cmax) Enzalutamide, M1,M2 and Enzalutamide Plus M2

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outcome · POSTED

AUC From the Time of Dosing to 24 h After Dosing (AUC24h) Enzalutamide, M1,M2 and Enzalutamide Plus M2

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outcome · POSTED

Concentration 24 h After Dosing (C24h) Enzalutamide, M1,M2 and Enzalutamide Plus M2

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outcome · POSTED

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

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outcome · POSTED

Apparent Total Systemic Clearance After Multiple Dosing (CL/F) Enzalutamide, M1,M2 and Enzalutamide Plus M2 (For Unchanged Enzalutamide Only)

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outcome · POSTED

Peak-Trough Ratio (PTR) Enzalutamide, M1,M2 and Enzalutamide Plus M2

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outcome · POSTED

AUC From the Time of Dosing to the Start of the Next Dosing Interval (AUCtau) Enzalutamide, M1,M2 and Enzalutamide Plus M2

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outcome · POSTED

Number of Participants With Adverse Events (AE)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: 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).
healthy Volunteers: false
minimum Age: 18 Years
sex: MALE
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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.
intervention Names
Drug: Enzalutamide
label
Enzalutamide
type
EXPERIMENTAL
description
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.
intervention Names
Drug: Placebo
label
Placebo
type
EXPERIMENTAL
description
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.
intervention Names
Drug: Enzalutamide
label
Placebo followed by Enzalutamide
type
EXPERIMENTAL

interventions

arm Group Labels
Enzalutamide
Placebo followed by Enzalutamide
description
Oral
name
Enzalutamide
other Names
Xtandi
MDV3100
type
DRUG
arm Group Labels
Placebo
description
Oral
name
Placebo
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: QUADRUPLE
who Masked: PARTICIPANT
CARE_PROVIDER
INVESTIGATOR
OUTCOMES_ASSESSOR

primary Purpose

TREATMENT

Enrollment

count: 395
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Time to Prostate-specific Antigen (PSA) Progression
time Frame
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 Outcomes

description
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.
measure
Duration of Overall Survival
time Frame
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
description
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.
measure
Duration of Radiographic Progression-free Survival (rPFS) Based on Independent Central Review Facility Assessment
time Frame
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
description
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.
measure
Time to First Skeletal-Related Event
time Frame
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
description
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.
measure
Time to Initiation of Cytotoxic Chemotherapy
time Frame
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
description
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.
measure
Number of Participants With Confirmed Best PSA Response (≥50% Decrease From Baseline)
time Frame
From baseline to the lowest post-baseline PSA result median treatment duration is 6.60 months for enzalutamide and 3.70 months for placebo
description
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.
measure
Best Overall Soft Tissue Response
time Frame
From the date of randomization median treatment duration is 6.60 months for enzalutamide and 3.70 months for placebo
measure
Time to Maximum Concentration (Tmax) of Enzalutamide, M1,M2 and Enzalutamide Plus M2
time Frame
From the date of randomization, Single Dosing Day 1 and Multiple Dosing Day 85
measure
Maximum Observed Plasma Concentration During the First 24 Hours After Dosing (Cmax) Enzalutamide, M1,M2 and Enzalutamide Plus M2
time Frame
From the date of randomization, Single Dosing Day 1 and Multiple Dosing Day 85
measure
AUC From the Time of Dosing to 24 h After Dosing (AUC24h) Enzalutamide, M1,M2 and Enzalutamide Plus M2
time Frame
From the date of randomization, Single Dosing Day 1 and Multiple Dosing Day 85
description
N is the number of participants with available data at this time point.
measure
Concentration 24 h After Dosing (C24h) Enzalutamide, M1,M2 and Enzalutamide Plus M2
time Frame
From the date of randomization, Single Dosing Day 1 and Multiple Dosing Day 85
description
N is the number of participants with available data at this time point.
measure
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
time Frame
From the date of randomization up to Days 2, 3, 8, 22, 29, 43, 57, 85, 86, 113, 141 and 169
measure
Apparent Total Systemic Clearance After Multiple Dosing (CL/F) Enzalutamide, M1,M2 and Enzalutamide Plus M2 (For Unchanged Enzalutamide Only)
time Frame
From the date of randomization up to Multiple Dosing Day 85

Full study description

brief Summary: 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.
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.

Source references

references

citation
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.
pmid
35397772
type
DERIVED