Clinical Trial Results:
A Phase 2, Single-Arm, Open-Label, Multicenter Study of the Clinical Activity and Safety of Enzalutamide in Subjects With Advanced, Androgen Receptor-Positive, Triple-Negative Breast Cancer.
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Summary
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EudraCT number |
2013-000698-57 |
Trial protocol |
GB BE IT IE ES |
Global end of trial date |
10 Jan 2024
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Results information
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Results version number |
v2(current) |
This version publication date |
04 Dec 2024
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First version publication date |
11 Aug 2018
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
C3431007
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01889238 | ||
WHO universal trial number (UTN) |
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Other trial identifiers |
Alias identifier: MDV3100-11 | ||
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Sponsors
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Sponsor organisation name |
Pfizer Inc.
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Sponsor organisation address |
66 East Hudson boulevard, New York, United States, NY 1001
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Public contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
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Scientific contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
15 Sep 2015
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
10 Jan 2024
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To determine the clinical benefit rate, defined as the proportion of evaluable subjects with androgen receptor positive (AR+) triple negative breast cancer (TNBC) with a best response of complete response (CR), partial response (PR), or stable disease (SD) greater than or equal (>=) 16 weeks.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
12 Jun 2013
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Belgium: 3
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Country: Number of subjects enrolled |
Canada: 9
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Country: Number of subjects enrolled |
United Kingdom: 9
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Country: Number of subjects enrolled |
Ireland: 6
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Country: Number of subjects enrolled |
Italy: 1
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Country: Number of subjects enrolled |
Spain: 16
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Country: Number of subjects enrolled |
United States: 74
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Worldwide total number of subjects |
118
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EEA total number of subjects |
26
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
74
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From 65 to 84 years |
44
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85 years and over |
0
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Recruitment
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Recruitment details |
Total of 118 subjects with advanced AR+ and TNBC were enrolled in this study. | ||||||||||||||||||
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Pre-assignment
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Screening details |
Subjects were enrolled at total of 34 study sites in North America and Europe to attain total of 78 evaluable subjects. | ||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Arm title
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Enzalutamide | ||||||||||||||||||
Arm description |
Subjects received enzalutamide 160 milligram (mg) (as four 40 mg soft gelatin capsules), orally once daily until disease progression (DP), intolerable adverse events (AEs) (including any seizures), noncompliance with protocol requirements, initiation of a new antitumor treatment, or subject or physician decision to discontinue treatment or death due to any cause. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Enzalutamide
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Investigational medicinal product code |
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Other name |
MDV3100
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Enzalutamide 160 mg was administered as four 40-mg soft gelatin capsules orally once daily.
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Baseline characteristics reporting groups
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Reporting group title |
Enzalutamide
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Reporting group description |
Subjects received enzalutamide 160 milligram (mg) (as four 40 mg soft gelatin capsules), orally once daily until disease progression (DP), intolerable adverse events (AEs) (including any seizures), noncompliance with protocol requirements, initiation of a new antitumor treatment, or subject or physician decision to discontinue treatment or death due to any cause. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Enzalutamide
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Reporting group description |
Subjects received enzalutamide 160 milligram (mg) (as four 40 mg soft gelatin capsules), orally once daily until disease progression (DP), intolerable adverse events (AEs) (including any seizures), noncompliance with protocol requirements, initiation of a new antitumor treatment, or subject or physician decision to discontinue treatment or death due to any cause. | ||
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End point title |
Percentage of Subjects With Clinical Benefit (CB) at Week 16: Evaluable Population [1] | ||||||||
End point description |
CB at Week16: percentage of subjects with best response of CR, PR, SD for>=16 weeks on radiologic imaging per investigator using RECIST version 1.1. Estimate of percentage, its exact 2-sided 85% confidence interval calculated by Blaker method. CR: disappearance of all target, non-target lesions, normalisation of tumor marker level, all lymph nodes decreased to non-pathological in size <10 millimeter(mm) short axis. PR: >=30% decrease in sum of longest diameter(LD) of target lesions taking as reference baseline sum of LD, without progression of non-target lesions, no appearance of new lesions. SD: neither sufficient reduction to qualify as PR nor sufficient increase to qualify as PD, using smallest sum diameters during study as reference. Evaluable population:enrolled subjects with centrally assessed AR+ breast cancer (total nuclear AR expression in >=10% of tumor cells), who received at least 1 dose of study drug with atleast 1 available post baseline tumor assessment per RECIST 1.1.
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End point type |
Primary
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End point timeframe |
Week 16
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses was planned. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects With CB at Week 16: Intent-to-Treat (ITT) Population [2] | ||||||||
End point description |
CB at Week 16 defined as percentage of subjects with a best response of CR, PR, or SD for >= 16 weeks on radiologic imaging based on investigator assessment using RECIST 1.1. An estimate of % and its exact 2-sided 85% CI were calculated using Blaker method. As per RECIST 1.1, CR defined as disappearance of all target, non-target lesions and normalization of tumor marker level and all lymph nodes decreased to non-pathological in size<10 mm short axis. PR: >=30% decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non-target lesions, no appearance of new lesions. SD: neither sufficient reduction to qualify as PR nor sufficient increase to qualify as PD, using smallest sum diameters during study as a reference. ITT population included all enrolled subjects who had centrally assessed AR+ breast cancer and received at least 1 dose of study drug.
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End point type |
Primary
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End point timeframe |
Week 16
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses was planned. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects With CB at Week 24: Evaluable Population | ||||||||
End point description |
CB at Week 24: percentage of subjects with a best response of CR, PR, or SD for >= 24 weeks on radiologic imaging per investigator using RECIST 1.1. Estimate of percentage, its exact 2-sided 85% CI was calculated by Blaker method. CR: disappearance of all target, non-target lesions, normalization of tumor marker level, all lymph nodes decreased to non-pathological in size <10 mm short axis. PR: At least 30% decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non-target lesions, no appearance of new lesions. SD: neither sufficient reduction to qualify as PR nor sufficient increase to qualify as PD, using the smallest sum diameters during the study as a reference. Evaluable population: enrolled subjects with centrally assessed AR + breast cancer (total nuclear AR expression in >= 10% of tumor cells), who received at least 1 dose of study drug with atleast 1 available post baseline tumor assessment per RECIST 1.1.
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End point type |
Secondary
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End point timeframe |
Week 24
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects With CB at Week 24: ITT Population | ||||||||
End point description |
CB at Week 24 defined as percentage of subjects with a best response of CR, PR, or SD for >= 24 weeks on radiologic imaging based on investigator assessment using RECIST 1.1. An estimate of the percentage and its exact 2-sided 85% CI were calculated using the Blaker method. As per RECIST 1.1, CR defined as disappearance of all target, non-target lesions and normalization of tumor marker level and all lymph nodes decreased to non-pathological in size <10 mm short axis. PR: At least 30% decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non-target lesions, no appearance of new lesions. SD: neither sufficient reduction to qualify as PR nor sufficient increase to qualify as PD, using the smallest sum diameters during the study as a reference. ITT population included all enrolled subjects who had centrally assessed AR+ breast cancer and received at least 1 dose of study drug.
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End point type |
Secondary
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End point timeframe |
Week 24
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects With Best Objective Response: Evaluable Population | ||||||||
End point description |
Percentage of subjects with best objective response defined as percentage of subjects with a best response of CR and PR based on investigator assessment of target, non-target and new lesions using RECIST 1.1. As per RECIST 1.1, CR defined as disappearance of all target, non-target lesions and normalization of tumor marker level and all lymph nodes decreased to non-pathological in <10 mm short axis. PR: At least 30% decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non-target lesions, no appearance of new lesions. Evaluable population: enrolled subjects with centrally assessed AR + breast cancer (total nuclear AR expression in >= 10% of tumor cells), who received at least 1 dose of study drug with atleast 1 available post baseline tumor assessment per RECIST 1.1. Here, Number of Subjects Analyzed signifies subjects evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
From Baseline up to disease progression or death due to any cause (up to 87 Weeks)
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects With Best Objective Response: ITT Population | ||||||||
End point description |
Percentage of subjects with best objective response defined as percentage of subjects with a best response of CR and PR based on investigator assessment of target, non-target and new lesions using RECIST 1.1. As per RECIST 1.1, CR defined as disappearance of all target, non-target lesions and normalization of tumor marker level and all lymph nodes decreased to non-pathological in <10 mm short axis. PR: At least 30% decrease in sum of LD of target lesions taking as reference baseline sum of LD, without progression of non-target lesions, no appearance of new lesions. ITT population included all enrolled subjects who had centrally assessed AR+ breast cancer and received at least 1 dose of study drug. Here, Number of Subjects Analyzed signifies subjects evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
From Baseline up to disease progression or death due to any cause (up to 87 Weeks)
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression-Free Survival (PFS): Evaluable Population | ||||||||
End point description |
PFS was defined as the time (in weeks) from the date of first dose of study drug to the date of documented disease progression or death due to any cause whichever occurs first as determined by the investigator using RECIST 1.1. As per RECIST 1.1, progression was defined as: >=20 percent increase in sum of LD of target lesions taking as a reference the smallest sum of the LD recorded since the treatment started, or the appearance of one or more new lesions and/or unequivocal progression of existing non target-lesions. Evaluable population included all enrolled subjects who had centrally assessed AR + breast cancer (total nuclear AR expression in >= 10% of tumor cells), had at least 1 dose of study drug and had at least 1 available post baseline tumor assessment evaluable as per RECIST 1.1.
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End point type |
Secondary
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End point timeframe |
From Baseline up to disease progression or death due to any cause (up to 87 Weeks)
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression-Free Survival: ITT Population | ||||||||
End point description |
PFS was defined as the time (in weeks) from the date of first dose of study drug to the date of documented disease progression or death due to any cause whichever occurs first as determined by the investigator using RECIST 1.1. As per RECIST 1.1, progression was defined as: >=20 percent increase in sum of LD of target lesions taking as a reference the smallest sum of the LD recorded since the treatment started, or the appearance of one or more new lesions and/or unequivocal progression of existing non target-lesions. ITT population included all enrolled subjects who had centrally assessed AR+ breast cancer and received at least 1 dose of study drug.
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End point type |
Secondary
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End point timeframe |
From Baseline up to disease progression or death due to any cause (up to 87 Weeks)
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to Response: Evaluable Population | ||||||||
End point description |
The time to response is defined as the time from the date of first dose of study drug to initial CR or PR. Subjects without response of CR or PR before the data cutoff date were censored at the last tumor assessment date before the data cutoff. Kaplan-Meier method was used to summarize time to response. Evaluable population included all enrolled subjects who had centrally assessed AR + breast cancer (total nuclear AR expression in >= 10% of tumor cells), had at least 1 dose of study drug and had at least 1 available post baseline tumor assessment evaluable as per RECIST 1.1. Here, 'Number of Subjects Analyzed' signifies subjects evaluable for this endpoint. '99999' indicates median and 95%CI could not be estimated due to insufficient number of subjects with the event.
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End point type |
Secondary
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End point timeframe |
From first dose of study drug until first documentation of CR or PR (up to 87 Weeks)
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| No statistical analyses for this end point | |||||||||
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End point title |
Duration of Response: Evaluable Population | ||||||||
End point description |
Duration of objective response was defined as the time from initial CR or PR to documented disease progression or death due to any cause, whichever occurs first. Subjects without disease progression or death due to any cause before the data cutoff date were censored at the last tumor assessment date before the data cutoff. Evaluable population included all enrolled subjects who had centrally assessed AR + breast cancer (total nuclear AR expression in >= 10% of tumor cells), had at least 1 dose of study drug and had at least 1 available post baseline tumor assessment evaluable as per RECIST 1.1. Here, 'Number of Subjects Analyzed' signifies subjects evaluable for this endpoint. '99999' indicates median and 95%CI could not be estimated due to insufficient number of subjects with the event.
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End point type |
Secondary
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End point timeframe |
From first documentation of CR or PR until first documentation of tumor progression or death due to any cause or data censoring date, whichever occurred first (up to 87 Weeks)
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Subjects With Postbaseline Laboratory Toxicities Grade 3 or 4 | ||||||||||||||||||||
End point description |
Laboratory parameters included hematology parameters [low lymphocytes (10^6/L), neutrophils (10^6/L) and Leukocytes (10^9/L)] and chemistry parameters [high phosphate (mmol/L), bilirubin, Alkaline phosphatase (U/L) and glucose (mmol/L)]. Number of participants with postbaseline laboratory toxicity Grade 3 or 4 as per NCI-CTCAE (version 4.0) (Grade 3= Severe, Grade 4= Life-threatening) were reported. Safety population included all subjects who received 1 dose or partial dose of study drug.
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End point type |
Secondary
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End point timeframe |
From start of study treatment on Day 1 up to 30 days after the last dose of study drug (up to maximum of 9.6 years)
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Trough Plasma Concentration of Enzalutamide and its Metabolite | ||||||||||||||||||||
End point description |
M2 was the metabolite of enzalutamide. The lower limit of of quantitation (LLQ) was 0.0200 micrograms per milliliter (mcg/mL) for enzalutamide and M2. Pharmacokinetics (PK) analysis population included all subjects who received 1 dose or partial dose of study drug, and who had at least 1 enzalutamide or M2 plasma concentration assessment. Here, 'Number of Subjects' Analyzed signifies subjects evaluable for this endpoint. Here, "99999" signifies that none of the subjects had data above LLQ and as per the predefined protocol, values below the limit of quantitation (BLQ) were set to missing and hence not reported.
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End point type |
Other pre-specified
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End point timeframe |
Predose on Day 1 (Baseline), Week 9 and Week 17
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Number of Subjects with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | ||||||||||
End point description |
An adverse event (AE) was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are events that were absent before treatment or that worsened relative to pretreatment state between first dose of study drug and up to 30 days after last dose of study drug or the day prior to initiation of new anti-tumor treatment. AEs included both serious and non-serious AEs. Safety population included all subjects who received 1 dose or partial dose of study drug.
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End point type |
Other pre-specified
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End point timeframe |
Baseline up to 87 weeks
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| No statistical analyses for this end point | |||||||||||
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End point title |
Number of Subjects With Study Drug Discontinuation due to Adverse Events | ||||||
End point description |
An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. Data reported here is for study drug discontinuation due to adverse events. Safety population included all subjects who received 1 dose or partial dose of study drug.
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End point type |
Other pre-specified
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End point timeframe |
Baseline up to 87 weeks
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Subjects With Grade 3 or Higher Adverse Events | ||||||
End point description |
An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. Severity of the AEs was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. As per the NCI CTCAE, version 4.0, Grade 3= severe or medically significant, Grade 4= life-threatening and Grade 5= death. Only the subjects with treatment-emergent AEs of Grade 3 (severe) or higher grade were reported in this endpoint. Safety population included all subjects who received 1 dose or partial dose of study drug
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End point type |
Other pre-specified
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End point timeframe |
Baseline up to 87 weeks
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Subjects With Clinically Significant Change From Baseline in Vital Signs | ||||||||||||||||||||||
End point description |
Criteria: Systolic blood pressure (SBP):absolute SBP<90 millimeters of mercury (mmHg) and decrease from baseline (DFB)>30mmHg, absolute SBP>180mmHg and increase from baseline (IFB)>40 mmHg, final visit or 2 consecutive visits SBP>=20 mmHg change from baseline (CFB), most extreme post-baseline SBP>=140mmHg, most extreme post-baseline SBP>=180mmHg, most extreme SBP>=140mmHg and>=20 mmHg CFB, most extreme SBP>=180mmHg and>=20mmHg CFB; diastolic blood pressure (DBP): absolute DBP>105mmHg and IFB>30mmHg, absolute DBP<50mmHg and DFB>20mmHg, final visit or 2 consecutive visits DBP>=15mmHg CFB, most extreme post-baseline DBP>=90mmHg, most extreme post-baseline DBP>=105mmHg, most extreme DBP>=90mmHg and>=15mmHg CFB, most extreme DBP>=105mmHg and>=15mmHg CFB; heart rate<50beats per minute (BPM) and DFB>20BPM or heart rate>120BPM and IFB>30BPM. Only those categories, in which at least 1 subject had data were reported. Safety population set was used in the analysis.
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End point type |
Other pre-specified
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End point timeframe |
From start of study treatment on Day 1 up to 30 days after the last dose of study drug (up to maximum of 9.6 years)
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| No statistical analyses for this end point | |||||||||||||||||||||||
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End point title |
Number of Subjects With Change From Baseline in Laboratory Parameters Grades by 2 or More Grades | ||||||||||||||||||||||||||||||||
End point description |
Laboratory tests included hematology parameters [low lymphocytes (10^6/L), white blood cells (10^9/L), neutrophils (10^6/L), hemoglobin gram per Liter(g/L) and platelets (10^9/L)] and chemistry parameters [mean albumin grams per Liter(g/L), calcium milli mole per Liter(mmol/L), Phosphate (mmol/L), alanine aminotransferase units per Liter(U/L), Aspartate aminotransferase (U/L), bilirubin micro mole per Liter, Alkaline phosphatase (U/L) and glucose (mmol/L)]. Number of participants with change from baseline in laboratory parameters Grades by 2 or More Grades as per NCI-CTCAE (version 4.0) (Grade 2=Moderate, Grade 3= Severe, Grade 4= Life-threatening) were reported. Safety population included all subjects who received 1 dose or partial dose of study drug.
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End point type |
Other pre-specified
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End point timeframe |
From start of study treatment on Day 1 up to 30 days after the last dose of study drug (up to maximum of 9.6 years)
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Baseline up to 87 weeks
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Adverse event reporting additional description |
Same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorised as serious in one subject and as non-serious in another subject or one subject may have experienced both a serious and non-serious event during the study.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.1
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Reporting groups
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Reporting group title |
Enzalutamide
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Reporting group description |
Subjects received enzalutamide 160 mg (as four 40 mg soft gelatin capsules), orally once daily until disease progression, intolerable AEs (including any seizures), noncompliance with protocol requirements, initiation of a new antitumor treatment, or subject or physician decision to discontinue treatment (up to a maximum of 87 Weeks). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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24 Oct 2013 |
1- Modified to require head imaging using magnetic resonance imaging (MRI) with contrast to rule out central nervous system (CNS) metastatic disease; head computed tomography (CT) with contrast could be considered after discussion with the medical monitor. Instructions for head imaging were provided for subjects enrolled before this amendment. 2- Increased the sample size from 80 to 95 subjects to ensure an adequate number of evaluable subjects for the primary and secondary efficacy endpoint analyses. 3- Modified exclusion criterion 10 to remove the option of using a creatinine clearance estimation by Cockcroft Gault. Renal function was to be assessed using a single parameter (serum creatinine) to enable analysis by common terminology criteria for adverse events (CTCAE) severity grading. 4- Clarified that modalities other than radiographic methods (such as physical examination) could be used for disease status assessments per RECIST 1.1; positron emission tomography (PET) imaging was not to be used. 5- Clarified that the primary efficacy endpoint of clinical benefit rate at 16 weeks was to be based on investigator determination of response using RECIST 1.1. 6- Provided guidance for late doses and updated the directions for dose modification. 7- Added instructions for reporting pregnancies. 8- Removed requirements for reporting certain adverse events as serious. |
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09 Dec 2016 |
1- Allows long-term follow-up that was previously continued until death to be discontinued at least 6 months after treatment discontinuation. 2- Reduces the assessments performed on patients continuing treatment after week 97 (approximately 2 years) to include only assessments of adverse events, concomitant medications, and study drug dispensation/accountability performed every 12 weeks. 3- Adds that patients continuing treatment after week 97 may enroll in an open-label extension study. 4- Adds that patients discontinuing treatment after week 97 will not participate in long-term follow-up. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
