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

Study Overview
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Brief Summary
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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.

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

Conditions
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Metastatic Castration-Resistant Prostate Cancer

Intervention / Treatment
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* Drug: Enzalutamide


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Enzalutamide<br>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<br>* Participants received 160 mg of enzalutamide (soft capsules) orally once daily.<br>* Other names: Xtandi;|

What is the study measuring?
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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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic Castration-Resistant Prostate Cancer, Enzalutamide, MDV3100, Xtandi, Abiraterone