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A Study to Evaluate Enzalutamide After Abiraterone in Metastatic Castration-Resistant Prostate Cancer

Primary Purpose

Metastatic Castration-Resistant Prostate Cancer

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Enzalutamide
Sponsored by
Astellas Pharma Europe B.V.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Castration-Resistant Prostate Cancer focused on measuring MDV3100, Xtandi, Abiraterone, Metastatic Castration-Resistant Prostate Cancer, Enzalutamide

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Subject has histologically confirmed adenocarcinoma of the prostate without neuro-endocrine differentiation or small cell features.
  • Subject has metastatic disease documented by bone scan or by soft tissue disease observed by Computed Tomography/Magnetic Resonance Imaging (CT/MRI) at screening, or within ≤30 days prior to Day 1.

  • In the setting of castrate levels of testosterone ≤1.7 nmol/L (or ≤50 ng/dL), subject has progressive disease at study entry defined as PSA rise determined by a minimum of 2 rising PSA levels with an interval of ≥ 1 week between each assessment. The PSA value at the screening visit should be ≥ 2 ng/mL WITH or WITHOUT:

    • Soft tissue disease progression defined by Response Evaluation Criteria In Solid Tumors (RECIST 1.1) at screening, or within ≤30 days prior to Day 1. Measurable disease is not required for entry. Lymph nodes ≥ 2 cm are considered measurable disease (Prostate Cancer Clinical Trials Working Group (PCWG2)).
    • Bone disease progression defined by at least 2 new lesions on bone scan at screening, or within ≤30 days prior to Day 1.
  • Subject must have received a minimum of 24 weeks of treatment with abiraterone acetate within its approved label indication and has discontinued use at least 4 weeks prior to start of study drug at Day 1.
  • If the subject has received previous treatment with chemotherapy for prostate cancer, this must be limited to no more than one prior line of docetaxel, and must have been used prior to abiraterone acetate therapy.
  • Subject receives and will continue to receive ongoing androgen deprivation with Luteinizing-hormone-releasing hormone (LHRH) analogue therapy throughout the course of the study or has had a bilateral orchiectomy.

  • Subject is asymptomatic or mildly symptomatic from prostate cancer:

    • The score on Brief Pain Inventory - Short Form (BPI-SF) Question #3 must be < 4.
    • No use of opiate analgesics for prostate cancer-related pain currently or anytime within 4 weeks prior to screening.

Exclusion Criteria:

  • Subject has prior use of ketoconazole for the treatment of prostate cancer.
  • Subject has prior use of cabazitaxel.
  • Subject has prior use of enzalutamide.
  • Subject has received ANY anti-neoplastic therapy (including antiandrogens and chemotherapy) following abiraterone acetate discontinuation and prior to start of study drug at Day 1.
  • Subject has a known or suspected hypersensitivity to enzalutamide, or any components of the formulation used.
  • Subject has known or suspected brain metastases or active leptomeningeal disease.
  • Subject has history of seizure or any condition that may predispose to seizure (e.g., prior stroke or significant brain trauma).

Sites / Locations

  • Site BE32001
  • Site BE32004
  • Site BE32007
  • Site BE32003
  • Site BE32002
  • Site FR33015
  • Site FR33009
  • Site FR33010
  • Site FR33014
  • Site FR33013
  • Site FR33003
  • Site FR33008
  • Site FR33002
  • Site FR33001
  • Site FR33011
  • Site FR33007
  • Site FR33005
  • Site FR33012
  • Site DE49005
  • Site DE49015
  • Site DE49017
  • Site DE49014
  • Site DE49003
  • Site DE49009
  • Site DE49010
  • Site DE49016
  • Site DE49004
  • Site DE49001
  • Site DE49008
  • Site DE49007
  • Site DE49002
  • Site DE49012
  • Site DE49006
  • Site ES34004
  • Site ES34009
  • Site ES34011
  • Site ES34006
  • Site ES34008
  • Site ES34001
  • Site ES34003
  • Site ES34002
  • Site ES34010
  • Site GB44001
  • Site GB44004
  • Site GB44009
  • Site GB44002
  • Site GB44007
  • Site GB44003
  • Site GB44010
  • Site GB44006

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Enzalutamide

Arm Description

Participants received 160 mg of enzalutamide orally once daily until they experienced an adverse event, disease progression, started new anti-cancer therapy, withdrew consent, or other protocol-specified criteria.

Outcomes

Primary Outcome Measures

Radiographic Progression-free Survival (rPFS)
Radiographic PFS, was defined as the time from first dose to the first objective evidence of radiographic disease progression or death from any cause, whichever occurred first. For patients with no documented progression event, it was censored on the date of the last disease assessment performed prior to the analysis data cut-off point. Radiographic progression (RP) for soft tissue disease was defined by Response Evaluation Criteria in Solid Tumors (RECIST) V1.1 criteria. RP for bone disease was determined according to the consensus guidelines of a modification of the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) guidelines. The 50th percentile of Kaplan-Meier (KM) estimates was used as the estimate of the rPFS median. A 2-sided 95% Confidence Interval (CI) was provided for this estimate using the Brookmeyer & Crowley (BC) method.

Secondary Outcome Measures

Overall Survival (OS)
OS was defined as the time from first dose to death from any cause. All events of death were included. If patients discontinued study drug before the analysis data cut-off point, only OS status was assessed every 12 weeks until the data cut-off point date or until death, whichever occurred first. For patients who were alive at the time of the analysis data cut-off point, the OS time was censored on the last date the patient was known to be alive. Death from any cause was included, regardless of whether the event occurred while the patient was still taking study drug or after the patient discontinued study drug. OS median was estimated using the KM method. A 2-sided 95% CI was provided for this estimate using the BC method.
Percentage of Participants With a Prostate-specific Antigen (PSA) Response
PSA response was defined as at least a 50% decrease from baseline in PSA, and was a binary variable for achieving this criteria (or not) based on the lowest PSA value observed postbaseline. Participants with no postbaseline PSA value were regarded as non-responders. 95% CI for PSA response rate was computed using the Clopper-Pearson method based on the exact binomial distribution.
Time to PSA Progression
The time to PSA progression was calculated as the time interval from the date of first dose to the date of first observation of PSA progression. PSA progression was defined as a ≥ 25% increase and an absolute increase of ≥ 2 μg/L (i.e., 2 ng/mL or more) above the nadir or above the baseline value for patients who did not have a decline in PSA postbaseline values, and which was confirmed by a second consecutive value obtained at least 3 or more weeks later (i.e., a confirmed rising trend) (PCWG2 criteria). The 50th percentile of KM estimates was used as the estimate of the time to PSA progression median. A 2-sided 95% CI was provided for this estimate using the BC method.
Number of Participants With Adverse Events (AEs)
A treatment-emergent adverse event (TEAE) was defined as an adverse event occurring or worsening between the start of study treatment date and the latest date of 30 days after the last dose date or the 30-day follow-up visit date, and not later than the data cut-off date or the date of death. AEs, including abnormal clinical laboratory values, were graded using the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) guidelines (V4.03).

Full Information

First Posted
April 15, 2014
Last Updated
October 16, 2018
Sponsor
Astellas Pharma Europe B.V.
Collaborators
Medivation, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02116582
Brief Title
A Study to Evaluate Enzalutamide After Abiraterone in Metastatic Castration-Resistant Prostate Cancer
Official Title
A Multi-center, Single Arm Study of Enzalutamide in Patients With Progressive Metastatic Castration-Resistant Prostate Cancer Previously Treated With Abiraterone Acetate
Study Type
Interventional

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
May 23, 2014 (Actual)
Primary Completion Date
May 8, 2016 (Actual)
Study Completion Date
September 29, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Astellas Pharma Europe B.V.
Collaborators
Medivation, Inc.

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

Brief Summary
The objective of this study was to evaluate the efficacy and safety of enzalutamide treatment in patients with progressive metastatic castration-resistant prostate cancer previously treated with abiraterone acetate.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Castration-Resistant Prostate Cancer
Keywords
MDV3100, Xtandi, Abiraterone, Metastatic Castration-Resistant Prostate Cancer, Enzalutamide

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
215 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Enzalutamide
Arm Type
Experimental
Arm Description
Participants received 160 mg of enzalutamide orally once daily until they experienced an adverse event, disease progression, started new anti-cancer therapy, withdrew consent, or other protocol-specified criteria.
Intervention Type
Drug
Intervention Name(s)
Enzalutamide
Other Intervention Name(s)
MDV3100, Xtandi
Intervention Description
Participants received 160 mg of enzalutamide (soft capsules) orally once daily.
Primary Outcome Measure Information:
Title
Radiographic Progression-free Survival (rPFS)
Description
Radiographic PFS, was defined as the time from first dose to the first objective evidence of radiographic disease progression or death from any cause, whichever occurred first. For patients with no documented progression event, it was censored on the date of the last disease assessment performed prior to the analysis data cut-off point. Radiographic progression (RP) for soft tissue disease was defined by Response Evaluation Criteria in Solid Tumors (RECIST) V1.1 criteria. RP for bone disease was determined according to the consensus guidelines of a modification of the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) guidelines. The 50th percentile of Kaplan-Meier (KM) estimates was used as the estimate of the rPFS median. A 2-sided 95% Confidence Interval (CI) was provided for this estimate using the Brookmeyer & Crowley (BC) method.
Time Frame
From the first dose of study drug administration up to treatment discontinuation or the data cut-off date of 08 May 2016, whichever occurred first; the median duration of treatment was 5.7 months.
Secondary Outcome Measure Information:
Title
Overall Survival (OS)
Description
OS was defined as the time from first dose to death from any cause. All events of death were included. If patients discontinued study drug before the analysis data cut-off point, only OS status was assessed every 12 weeks until the data cut-off point date or until death, whichever occurred first. For patients who were alive at the time of the analysis data cut-off point, the OS time was censored on the last date the patient was known to be alive. Death from any cause was included, regardless of whether the event occurred while the patient was still taking study drug or after the patient discontinued study drug. OS median was estimated using the KM method. A 2-sided 95% CI was provided for this estimate using the BC method.
Time Frame
From the first dose of study drug administration up to the data cut-off date of 08 May 2016; up to 2 years.
Title
Percentage of Participants With a Prostate-specific Antigen (PSA) Response
Description
PSA response was defined as at least a 50% decrease from baseline in PSA, and was a binary variable for achieving this criteria (or not) based on the lowest PSA value observed postbaseline. Participants with no postbaseline PSA value were regarded as non-responders. 95% CI for PSA response rate was computed using the Clopper-Pearson method based on the exact binomial distribution.
Time Frame
From the first dose of study drug administration up to the data cut-off date for end-of-study completion 29 Sep 2017; the median duration of treatment was 5.7 months.
Title
Time to PSA Progression
Description
The time to PSA progression was calculated as the time interval from the date of first dose to the date of first observation of PSA progression. PSA progression was defined as a ≥ 25% increase and an absolute increase of ≥ 2 μg/L (i.e., 2 ng/mL or more) above the nadir or above the baseline value for patients who did not have a decline in PSA postbaseline values, and which was confirmed by a second consecutive value obtained at least 3 or more weeks later (i.e., a confirmed rising trend) (PCWG2 criteria). The 50th percentile of KM estimates was used as the estimate of the time to PSA progression median. A 2-sided 95% CI was provided for this estimate using the BC method.
Time Frame
From the first dose of study drug administration up to the data cut-off date of 08 May 2016; the median duration of treatment was 5.7 months.
Title
Number of Participants With Adverse Events (AEs)
Description
A treatment-emergent adverse event (TEAE) was defined as an adverse event occurring or worsening between the start of study treatment date and the latest date of 30 days after the last dose date or the 30-day follow-up visit date, and not later than the data cut-off date or the date of death. AEs, including abnormal clinical laboratory values, were graded using the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) guidelines (V4.03).
Time Frame
From the first dose of study drug administration up to data cut-off date for end-of-study completion (29 Sep 2017); the median duration of treatment was 5.7 months.

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subject has histologically confirmed adenocarcinoma of the prostate without neuro-endocrine differentiation or small cell features. Subject has metastatic disease documented by bone scan or by soft tissue disease observed by Computed Tomography/Magnetic Resonance Imaging (CT/MRI) at screening, or within ≤30 days prior to Day 1. In the setting of castrate levels of testosterone ≤1.7 nmol/L (or ≤50 ng/dL), subject has progressive disease at study entry defined as PSA rise determined by a minimum of 2 rising PSA levels with an interval of ≥ 1 week between each assessment. The PSA value at the screening visit should be ≥ 2 ng/mL WITH or WITHOUT: Soft tissue disease progression defined by Response Evaluation Criteria In Solid Tumors (RECIST 1.1) at screening, or within ≤30 days prior to Day 1. Measurable disease is not required for entry. Lymph nodes ≥ 2 cm are considered measurable disease (Prostate Cancer Clinical Trials Working Group (PCWG2)). Bone disease progression defined by at least 2 new lesions on bone scan at screening, or within ≤30 days prior to Day 1. Subject must have received a minimum of 24 weeks of treatment with abiraterone acetate within its approved label indication and has discontinued use at least 4 weeks prior to start of study drug at Day 1. If the subject has received previous treatment with chemotherapy for prostate cancer, this must be limited to no more than one prior line of docetaxel, and must have been used prior to abiraterone acetate therapy. Subject receives and will continue to receive ongoing androgen deprivation with Luteinizing-hormone-releasing hormone (LHRH) analogue therapy throughout the course of the study or has had a bilateral orchiectomy. Subject is asymptomatic or mildly symptomatic from prostate cancer: The score on Brief Pain Inventory - Short Form (BPI-SF) Question #3 must be < 4. No use of opiate analgesics for prostate cancer-related pain currently or anytime within 4 weeks prior to screening. Exclusion Criteria: Subject has prior use of ketoconazole for the treatment of prostate cancer. Subject has prior use of cabazitaxel. Subject has prior use of enzalutamide. Subject has received ANY anti-neoplastic therapy (including antiandrogens and chemotherapy) following abiraterone acetate discontinuation and prior to start of study drug at Day 1. Subject has a known or suspected hypersensitivity to enzalutamide, or any components of the formulation used. Subject has known or suspected brain metastases or active leptomeningeal disease. Subject has history of seizure or any condition that may predispose to seizure (e.g., prior stroke or significant brain trauma).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Astellas Pharma Europe B.V.
Official's Role
Study Director
Facility Information:
Facility Name
Site BE32001
City
Brussels
State/Province
Flemish Brabant
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Site BE32004
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Site BE32007
City
Hasselt
ZIP/Postal Code
3500
Country
Belgium
Facility Name
Site BE32003
City
Kortrijk
ZIP/Postal Code
8500
Country
Belgium
Facility Name
Site BE32002
City
Liege
ZIP/Postal Code
4000
Country
Belgium
Facility Name
Site FR33015
City
Angers cedex 02
ZIP/Postal Code
49055
Country
France
Facility Name
Site FR33009
City
Caen Cedex 05
ZIP/Postal Code
14076
Country
France
Facility Name
Site FR33010
City
Creteil cedex
ZIP/Postal Code
94010
Country
France
Facility Name
Site FR33014
City
Le Mans
ZIP/Postal Code
72015
Country
France
Facility Name
Site FR33013
City
Lyon Cedex 3
ZIP/Postal Code
69003
Country
France
Facility Name
Site FR33003
City
Marseille CEDEX 9
ZIP/Postal Code
13273
Country
France
Facility Name
Site FR33008
City
Nantes Saint Herblain Cedex
ZIP/Postal Code
44805
Country
France
Facility Name
Site FR33002
City
Nimes
ZIP/Postal Code
30029
Country
France
Facility Name
Site FR33001
City
Paris cedex 15
ZIP/Postal Code
75908
Country
France
Facility Name
Site FR33011
City
Paris
ZIP/Postal Code
75005
Country
France
Facility Name
Site FR33007
City
Rennes
ZIP/Postal Code
35042
Country
France
Facility Name
Site FR33005
City
Suresnes
ZIP/Postal Code
92151
Country
France
Facility Name
Site FR33012
City
Villejiuf
ZIP/Postal Code
94805
Country
France
Facility Name
Site DE49005
City
Nuertingen
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
72622
Country
Germany
Facility Name
Site DE49015
City
Bergisch Gladbach
State/Province
Northwest
ZIP/Postal Code
51427
Country
Germany
Facility Name
Site DE49017
City
Duisburg
State/Province
NRW
ZIP/Postal Code
47179
Country
Germany
Facility Name
Site DE49014
City
Berlin
ZIP/Postal Code
10247
Country
Germany
Facility Name
Site DE49003
City
Berlin
ZIP/Postal Code
12200
Country
Germany
Facility Name
Site DE49009
City
Bonn
ZIP/Postal Code
53111
Country
Germany
Facility Name
Site DE49010
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Site DE49016
City
Duesseldorf
ZIP/Postal Code
40225
Country
Germany
Facility Name
Site DE49004
City
Goettingen
ZIP/Postal Code
37075
Country
Germany
Facility Name
Site DE49001
City
Hamburg
ZIP/Postal Code
22081
Country
Germany
Facility Name
Site DE49008
City
Hamburg
ZIP/Postal Code
22399
Country
Germany
Facility Name
Site DE49007
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Site DE49002
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Site DE49012
City
Munster
ZIP/Postal Code
48149
Country
Germany
Facility Name
Site DE49006
City
Tubingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
Site ES34004
City
Santiago de Compostela
State/Province
A Coruna
ZIP/Postal Code
15706
Country
Spain
Facility Name
Site ES34009
City
Badalona
ZIP/Postal Code
8916
Country
Spain
Facility Name
Site ES34011
City
Barcelona
ZIP/Postal Code
08003
Country
Spain
Facility Name
Site ES34006
City
Barcelona
ZIP/Postal Code
08025
Country
Spain
Facility Name
Site ES34008
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Site ES34001
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Site ES34003
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Site ES34002
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Site ES34010
City
Madrid
ZIP/Postal Code
28044
Country
Spain
Facility Name
Site GB44001
City
Sutton
State/Province
Surrey
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
Facility Name
Site GB44004
City
Birmingham
ZIP/Postal Code
B15 2TT
Country
United Kingdom
Facility Name
Site GB44009
City
Brighton
ZIP/Postal Code
BN2 5BE
Country
United Kingdom
Facility Name
Site GB44002
City
Glasgow
ZIP/Postal Code
G12 0YN
Country
United Kingdom
Facility Name
Site GB44007
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
Facility Name
Site GB44003
City
Northwood, Middlesex
ZIP/Postal Code
HA6 2RN
Country
United Kingdom
Facility Name
Site GB44010
City
Plymouth
ZIP/Postal Code
PL6 8DH
Country
United Kingdom
Facility Name
Site GB44006
City
Withington
ZIP/Postal Code
M204BX
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Access to anonymized individual participant level data collected during the trial, in addition to study-related supporting documentation, is planned for trials conducted with approved product indications and formulations, as well as compounds terminated during development. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
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 URL
https://www.clinicalstudydatarequest.com/
Citations:
PubMed Identifier
28844372
Citation
de Bono JS, Chowdhury S, Feyerabend S, Elliott T, Grande E, Melhem-Bertrandt A, Baron B, Hirmand M, Werbrouck P, Fizazi K. Antitumour Activity and Safety of Enzalutamide in Patients with Metastatic Castration-resistant Prostate Cancer Previously Treated with Abiraterone Acetate Plus Prednisone for >/=24 weeks in Europe. Eur Urol. 2018 Jul;74(1):37-45. doi: 10.1016/j.eururo.2017.07.035. Epub 2017 Aug 23.
Results Reference
derived
Links:
URL
https://astellasclinicalstudyresults.com/study.aspx?ID=274
Description
Link to results on the Astellas Clinical Study Results website

Learn more about this trial

A Study to Evaluate Enzalutamide After Abiraterone in Metastatic Castration-Resistant Prostate Cancer

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