Clinical trial NCT02294461: An Asian Study to Evaluate Efficacy and Safety of Oral Enzalutamide in Progressive Metastatic Prostate Cancer Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Progressive Metastatic Prostate Cancer
Keywords: Enzalutamide
Androgen receptor
Prostate cancer
Xtandi
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2014-11-19
Enrollment: 395
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Time to Prostate-specific Antigen (PSA) Progression
timeFrame: From randomization up to data cut off date of 20 Sept 2015; median follow-up time is 7.33 months for enzalutamide and 3.02 months for placebo
Secondary outcomes:
measure: Duration of Overall Survival
timeFrame: From randomization up to data cutoff date of 04 Nov 2020; median follow-up time is 21.9 months for enzalutamide and 7.29 months for placebo
measure: Duration of Radiographic Progression-free Survival (rPFS) Based on Independent Central Review Facility Assessment
timeFrame: From randomization up to data cutoff date of 20 Sept 2015; median follow-up time is 5.55 months for enzalutamide and 3.71 months for placebo
measure: Time to First Skeletal-Related Event
timeFrame: From randomization up to data cutoff date of 20 Sept 2015; median follow-up time is 7.39 months for enzalutamide and 5.29 months for placebo
measure: Time to Initiation of Cytotoxic Chemotherapy
timeFrame: From randomization up to data cutoff date of 20 Sept 2015; median follow-up time is 7.39 months for enzalutamide and 4.93 months for placebo
measure: Number of Participants With Confirmed Best PSA Response (≥50% Decrease From Baseline)
timeFrame: Baseline up to data cut off date of 20 Sept 2015; median treatment duration is 6.60 months for enzalutamide and 3.70 months for placebo
measure: Best Overall Soft Tissue Response
timeFrame: From randomization up to data cut off date of 20 Sept 2015; 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
timeFrame: From randomization up to data cutoff date of 20 Jan 2016; 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
timeFrame: From randomization up to data cutoff date of 20 Jan 2016; 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
timeFrame: From randomization up to data cutoff date of 20 Jan 2016; Single Dosing Day 1
measure: Concentration 24 h After Dosing (C24h) Enzalutamide, M1,M2 and Enzalutamide Plus M2
timeFrame: From randomization up to data cutoff date of 20 Jan 2016; Single Dosing Day 1 and Multiple Dosing Day 85
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
timeFrame: From randomization up to data cutoff date of 20 Jan 2016; Day 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)
timeFrame: From randomization up to data cutoff date of 20 Jan 2016; Multiple Dosing Day 85
measure: Peak-Trough Ratio (PTR) Enzalutamide, M1,M2 and Enzalutamide Plus M2
timeFrame: From randomization up to data cutoff date of 20 Jan 2016; Multiple Dosing Day 85
measure: AUC From the Time of Dosing to the Start of the Next Dosing Interval (AUCtau) Enzalutamide, M1,M2 and Enzalutamide Plus M2
timeFrame: From randomization up to data cutoff date of 20 Jan 2016; Multiple Dosing Day 85
measure: Number of Participants With Adverse Events (AE)
timeFrame: From first dose of study drug up to data cut off date of 04 Nov. 2020(up to 18.6 months for 'Placebo'; up to 4 weeks after last dose of enzalutamide-up to 84.7 months for 'Enzalutamide' and up to 54.8 months for 'Placebo followed by Enzalutamide')
Other outcomes:
Locations:
city: Beijing
country: China
facility: CN00103
city: Beijing
country: China
facility: CN00104
city: Beijing
country: China
facility: CN00106
city: Beijing
country: China
facility: CN00111
city: Beijing
country: China
facility: CN00112
city: Beijing
country: China
facility: CN00114
city: Beijing
country: China
facility: CN00115
city: Beijing
country: China
facility: CN00127
city: Changsha
country: China
facility: CN00121
city: Hangzhou
country: China
facility: CN00107
city: Nanjing
country: China
facility: CN00110
city: Nanjing
country: China
facility: CN00117
city: Shanghai
country: China
facility: CN00102
city: Shanghai
country: China
facility: CN00105
city: Shanghai
country: China
facility: CN00108
city: Shanghai
country: China
facility: CN00113
city: Shanghai
country: China
facility: CN00126
city: Soochow
country: China
facility: CN00119
city: Tianjin
country: China
facility: CN00125
city: Wenzhou
country: China
facility: CN00118
city: Wu Han
country: China
facility: CN00109
city: Xi'an
country: China
facility: CN00124
city: Hong Kong
country: Hong Kong
facility: HK00402
city: Anyang
country: Korea, Republic of
facility: KR00214
city: Busan
country: Korea, Republic of
facility: KR00205
city: Busan
country: Korea, Republic of
facility: KR00207
city: Cheongju
country: Korea, Republic of
facility: KR00212
city: Daegu
country: Korea, Republic of
facility: KR00203
city: Daejeon
country: Korea, Republic of
facility: KR00213
city: Incheon
country: Korea, Republic of
facility: KR00201
city: Seongnam-si
country: Korea, Republic of
facility: KR00202
city: Seoul
country: Korea, Republic of
facility: KR00204
city: Seoul
country: Korea, Republic of
facility: KR00206
city: Seoul
country: Korea, Republic of
facility: KR00208
city: Seoul
country: Korea, Republic of
facility: KR00209
city: Seoul
country: Korea, Republic of
facility: KR00210
city: Seoul
country: Korea, Republic of
facility: KR00211
city: Seoul
country: Korea, Republic of
facility: KR00215
city: Kaohsiung
country: Taiwan
facility: TW00309
city: Taichung
country: Taiwan
facility: TW00302
city: Taichung
country: Taiwan
facility: TW00303
city: Tainan
country: Taiwan
facility: TW00307
city: Tainan
country: Taiwan
facility: TW00308
city: Taipei
country: Taiwan
facility: TW00301
city: Taipei
country: Taiwan
facility: TW00304
city: Taipei
country: Taiwan
facility: TW00306
city: Taoyuan County
country: Taiwan
facility: TW00305
Study officials:
affiliation: Astellas Pharma Inc
name: Central Contact
role: STUDY_DIRECTOR
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.