Clinical trial NCT02116582: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Metastatic Castration-Resistant Prostate Cancer
Keywords: MDV3100
Xtandi
Abiraterone
Metastatic Castration-Resistant Prostate Cancer
Enzalutamide
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
First posted: 2014-04-17
Enrollment: 215
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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).

Primary outcomes:
measure: Radiographic Progression-free Survival (rPFS)
timeFrame: 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 outcomes:
measure: Overall Survival (OS)
timeFrame: From the first dose of study drug administration up to the data cut-off date of 08 May 2016; up to 2 years.
measure: Percentage of Participants With a Prostate-specific Antigen (PSA) Response
timeFrame: 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.
measure: Time to PSA Progression
timeFrame: 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.
measure: Number of Participants With Adverse Events (AEs)
timeFrame: 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.
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Site BE32001
state: Flemish Brabant
city: Gent
country: Belgium
facility: Site BE32004
city: Hasselt
country: Belgium
facility: Site BE32007
city: Kortrijk
country: Belgium
facility: Site BE32003
city: Liege
country: Belgium
facility: Site BE32002
city: Angers cedex 02
country: France
facility: Site FR33015
city: Caen Cedex 05
country: France
facility: Site FR33009
city: Creteil cedex
country: France
facility: Site FR33010
city: Le Mans
country: France
facility: Site FR33014
city: Lyon Cedex 3
country: France
facility: Site FR33013
city: Marseille CEDEX 9
country: France
facility: Site FR33003
city: Nantes Saint Herblain Cedex
country: France
facility: Site FR33008
city: Nimes
country: France
facility: Site FR33002
city: Paris cedex 15
country: France
facility: Site FR33001
city: Paris
country: France
facility: Site FR33011
city: Rennes
country: France
facility: Site FR33007
city: Suresnes
country: France
facility: Site FR33005
city: Villejiuf
country: France
facility: Site FR33012
city: Nuertingen
country: Germany
facility: Site DE49005
state: Baden-Wuerttemberg
city: Bergisch Gladbach
country: Germany
facility: Site DE49015
state: Northwest
city: Duisburg
country: Germany
facility: Site DE49017
state: NRW
city: Berlin
country: Germany
facility: Site DE49014
city: Berlin
country: Germany
facility: Site DE49003
city: Bonn
country: Germany
facility: Site DE49009
city: Dresden
country: Germany
facility: Site DE49010
city: Duesseldorf
country: Germany
facility: Site DE49016
city: Goettingen
country: Germany
facility: Site DE49004
city: Hamburg
country: Germany
facility: Site DE49001
city: Hamburg
country: Germany
facility: Site DE49008
city: Hannover
country: Germany
facility: Site DE49007
city: Heidelberg
country: Germany
facility: Site DE49002
city: Munster
country: Germany
facility: Site DE49012
city: Tubingen
country: Germany
facility: Site DE49006
city: Santiago de Compostela
country: Spain
facility: Site ES34004
state: A Coruna
city: Badalona
country: Spain
facility: Site ES34009
city: Barcelona
country: Spain
facility: Site ES34011
city: Barcelona
country: Spain
facility: Site ES34006
city: Barcelona
country: Spain
facility: Site ES34008
city: Madrid
country: Spain
facility: Site ES34001
city: Madrid
country: Spain
facility: Site ES34003
city: Madrid
country: Spain
facility: Site ES34002
city: Madrid
country: Spain
facility: Site ES34010
city: Sutton
country: United Kingdom
facility: Site GB44001
state: Surrey
city: Birmingham
country: United Kingdom
facility: Site GB44004
city: Brighton
country: United Kingdom
facility: Site GB44009
city: Glasgow
country: United Kingdom
facility: Site GB44002
city: London
country: United Kingdom
facility: Site GB44007
city: Northwood, Middlesex
country: United Kingdom
facility: Site GB44003
city: Plymouth
country: United Kingdom
facility: Site GB44010
city: Withington
country: United Kingdom
facility: Site GB44006
Study officials:
affiliation: Astellas Pharma Europe B.V.
name: Medical Director
role: STUDY_DIRECTOR
References:
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.