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

A Multi-center, Single Arm Study of Enzalutamide in Patients With Progressive Metastatic Castration-Resistant Prostate Cancer Previously Treated With Abiraterone Acetate

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Castration-Resistant Prostate Cancer
• Intervention / Treatment: Drug: Enzalutamide

• Study Type: Interventional
• Enrollment (Actual): 215
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • Site BE32004
  • Hasselt, Belgium, 3500
    • Site BE32007
  • Kortrijk, Belgium, 8500
    • Site BE32003
  • Liege, Belgium, 4000
    • Site BE32002
  • Flemish Brabant
    • Brussels, Flemish Brabant, Belgium, 1200
      • Site BE32001
• France
  • Angers cedex 02, France, 49055
    • Site FR33015
  • Caen Cedex 05, France, 14076
    • Site FR33009
  • Creteil cedex, France, 94010
    • Site FR33010
  • Le Mans, France, 72015
    • Site FR33014
  • Lyon Cedex 3, France, 69003
    • Site FR33013
  • Marseille CEDEX 9, France, 13273
    • Site FR33003
  • Nantes Saint Herblain Cedex, France, 44805
    • Site FR33008
  • Nimes, France, 30029
    • Site FR33002
  • Paris, France, 75005
    • Site FR33011
  • Paris cedex 15, France, 75908
    • Site FR33001
  • Rennes, France, 35042
    • Site FR33007
  • Suresnes, France, 92151
    • Site FR33005
  • Villejiuf, France, 94805
    • Site FR33012
• Germany
  • Berlin, Germany, 10247
    • Site DE49014
  • Berlin, Germany, 12200
    • Site DE49003
  • Bonn, Germany, 53111
    • Site DE49009
  • Dresden, Germany, 01307
    • Site DE49010
  • Duesseldorf, Germany, 40225
    • Site DE49016
  • Goettingen, Germany, 37075
    • Site DE49004
  • Hamburg, Germany, 22081
    • Site DE49001
  • Hamburg, Germany, 22399
    • Site DE49008
  • Hannover, Germany, 30625
    • Site DE49007
  • Heidelberg, Germany, 69120
    • Site DE49002
  • Munster, Germany, 48149
    • Site DE49012
  • Tubingen, Germany, 72076
    • Site DE49006
  • Baden-Wuerttemberg
    • Nuertingen, Baden-Wuerttemberg, Germany, 72622
      • Site DE49005
  • NRW
    • Duisburg, NRW, Germany, 47179
      • Site DE49017
  • Northwest
    • Bergisch Gladbach, Northwest, Germany, 51427
      • Site DE49015
• Spain
  • Badalona, Spain, 8916
    • Site ES34009
  • Barcelona, Spain, 08003
    • Site ES34011
  • Barcelona, Spain, 08025
    • Site ES34006
  • Barcelona, Spain, 08035
    • Site ES34008
  • Madrid, Spain, 28007
    • Site ES34001
  • Madrid, Spain, 28034
    • Site ES34003
  • Madrid, Spain, 28040
    • Site ES34002
  • Madrid, Spain, 28044
    • Site ES34010
  • A Coruna
    • Santiago de Compostela, A Coruna, Spain, 15706
      • Site ES34004
• United Kingdom
  • Birmingham, United Kingdom, B15 2TT
    • Site GB44004
  • Brighton, United Kingdom, BN2 5BE
    • Site GB44009
  • Glasgow, United Kingdom, G12 0YN
    • Site GB44002
  • London, United Kingdom, SE1 9RT
    • Site GB44007
  • Northwood, Middlesex, United Kingdom, HA6 2RN
    • Site GB44003
  • Plymouth, United Kingdom, PL6 8DH
    • Site GB44010
  • Withington, United Kingdom, M204BX
    • Site GB44006
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • Site GB44001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Enzalutamide; 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.	Drug: Enzalutamide; Participants received 160 mg of enzalutamide (soft capsules) orally once daily.; Other Names: Xtandi; MDV3100

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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 Measures

Outcome Measure	Measure Description	Time Frame
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.	From the first dose of study drug administration up to the data cut-off date of 08 May 2016; up to 2 years.
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.	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.
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.	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.
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).	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.

Collaborators and Investigators

• Sponsor: Astellas Pharma Europe B.V.
• Collaborators: Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
• Investigators: Study Director: Medical Director, Astellas Pharma Europe B.V.

Publications and helpful links

General Publications

• 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.

Helpful Links

• Link to results on the Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2014
• Primary Completion (Actual): May 8, 2016
• Study Completion (Actual): September 29, 2017

Study Registration Dates

• First Submitted: April 15, 2014
• First Submitted That Met QC Criteria: April 15, 2014
• First Posted (Estimated): April 17, 2014

Study Record Updates

• Last Update Posted (Actual): December 6, 2024
• Last Update Submitted That Met QC Criteria: November 19, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Xtandi; MDV3100; Enzalutamide; Abiraterone; Metastatic Castration-Resistant Prostate Cancer
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 9785-CL-0410; 2013-002271-17 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
• 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 Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• 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