A Study to Test if Enzalutamide is Effective and Safe in Prostate Cancer Patients Who Have Never Had Hormone Therapy

Study Overview
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Brief Summary
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To evaluate the effect of enzalutamide on prostate specific antigen (PSA) level in men with prostate cancer.

Official Title
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A Phase 2, Open-label, Single-arm, Efficacy and Safety Study of Enzalutamide (MDV3100) in Patients With Hormone-naïve Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Enzalutamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed prostate cancer (all stages) for whom androgen deprivation therapy is indicated (except when indicated in a neoadjuvant/adjuvant therapy) Asymptomatic from prostate cancer Non-castrate level of testosterone (≥ 8 nmol/L (230 ng/dL)) at screening PSA ≥ 2 ng/mL at screening Exclusion Criteria: Has previously or is currently receiving: Hormonal therapy with intent to treat prostate cancer Systemic glucocorticoids Chemotherapy with the intent to treat prostate cancer Opiate analgesics for pain from prostate cancer Radiation therapy for treatment of the primary tumor or metastases Has history of known or suspected brain or skull metastases or leptomeningeal disease Has history of seizure including febrile seizure or any condition that may predispose to seizure or history of loss of consciousness or transient ischemic attack Clinically significant cardiovascular disease

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 oral enzalutamide at 160 mg once daily for 24 weeks. Participants who had clinical benefit at Week 25 could continue to receive enzalutamide until disease progression, objective or clinical, or occurrence of an unacceptable toxicity, at the discretion of the investigator. | Drug: Enzalutamide<br>* Oral<br>* Other names: MDV3100;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Prostate-Specific Antigen (PSA) Response at Week 25 | A PSA response was defined as a decline from Baseline in PSA level of 80% or greater. Blood samples for PSA were collected and analyzed at a central laboratory. Participants with an unknown or missing response or who discontinued prior to week 25 for any reason were treated as non-responders. | Baseline and Week 25 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | Each adverse event (AE) was assessed by the investigator for causal relationship to the study drug; those deemed possibly or probably related to study drug are reported as drug regimen related AEs (DRRAEs). A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose: Resulted in death Was life-threatening Resulted in persistent or significant disability/incapacity Resulted in congenital anomaly or birth defect Required inpatient hospitalization or led to prolongation of hospitalization Other medically important events. | From first dose of study drug up to 30 days after last dose of study drug; median duration of treatment of 1666.0 days (range of 52-2052) | 
| Percent Change From Baseline in PSA |  | Baseline and Weeks 25, 49, 97, 169 and Week 265 (End of Study) | 
| Percent Change From Baseline in Sex Hormone-Binding Globulin (SHBG) |  | Baseline and Weeks 25 and 49 | 
| Percent Change From Baseline in Androstenedione |  | Baseline and Weeks 25 and 49 | 
| Percent Change From Baseline in Dehydroepiandrosterone (DHEA) |  | Baseline and Weeks 25 and 49 | 
| Percent Change From Baseline in Dihydrotestosterone (DHT) |  | Baseline and Week 25 and 49 | 
| Percent Change From Baseline in Estradiol |  | Baseline and Weeks 25 and 49 | 
| Percent Change From Baseline in Follicle-Stimulating Hormone (FSH) |  | Baseline and Weeks 25 and 49 | 
| Percent Change From Baseline in Luteinizing Hormone (LH) |  | Baseline and Weeks 25 and 49 | 
| Percent Change From Baseline in Prolactin |  | Baseline and Weeks 25 and 49 | 
| Percent Change From Baseline in Total Testosterone |  | Baseline and Weeks 25 and 49 | 
| Percent Change From Baseline in Free Testosterone |  | Baseline and Weeks 25 and 49 | 
| Plasma Concentration of Enzalutamide at Pre-dose (Ctrough) |  | Pre-dose at Weeks 2, 3, 4, 5, 9, 13, 21 and 25 | 
| Plasma Concentration of Enzalutamide Metabolite M2 at Pre-dose (Ctrough) |  | Pre-dose at Weeks 2, 3, 4, 5, 9, 13, 21 and 25 | 
| Percentage of Participants With a PSA Response at Weeks 49, 97 and 169 | A PSA response was defined as a decline from baseline in PSA level of 80% or greater. Blood samples for PSA were collected and analyzed at a central laboratory. Participants with an unknown or missing response or who discontinued prior to week 49, week 97 or week 169 for any reason were treated as non-responders. | Baseline and Weeks 49, 97 and 169 | 
| Percentage of Participants With a 90% or Greater Reduction From Baseline in PSA Level | Participants with unknown or missing PSA results at week 25 or who discontinued prior to week 25 were considered non-responders at week 25. Participants with unknown or missing PSA results at week 49, week 97 or week 169 were considered non-responders. | Baseline and Weeks 25, 49, 97 and 169 | 
| Percentage of Participants With PSA ≤ 4 ng/ml | Participants with unknown or missing PSA results at week 25 or who discontinued prior to Week 25 were considered non-responders at Week 25. Participants with unknown or missing PSA results at week 49, 97 and 169 were considered non-responders. | Weeks 25, 49, 97 and 169 | 
| Percentage of Participants With PSA ≤ 0.1 ng/ml | Participants with unknown or missing PSA results at week 25 or who discontinued prior to week 25 were considered non-responders at week 25. Participants with unknown or missing PSA results at week 49, 97 or 169 were considered non-responders. | Weeks 25, 49, 97 and 169 | 
| Maximum Decline From Baseline in PSA | The maximum decline from Baseline in PSA was calculated as the largest reduction from Baseline in PSA level that occurred at any point after treatment start up to week 25 and up to and including the assessment made at the safety follow-up visit, divided by the PSA Baseline value and multiplied by 100, i.e., the maximum percent change from baseline. | Baseline to Week 25 and from Baseline up to the EOS date of 27 Apr 2017; median duration of treatment of 1666.0 days (range of 52-2052) | 
| Time to PSA Response | Time to PSA response (PSA decline ≥ 80% from Baseline) is defined as the time interval from the first study drug dose to the first date a decline from Baseline in PSA level of 80% or greater was recorded. Time to response was estimated using the Kaplan-Meier method. | From first dose until the EOS date of 27-Apr-2017; median duration of treatment of 1666.0 days (range of 52-2052) | 
| Time to PSA Decline ≥ 90% | Time to PSA decline ≥ 90% is defined as the time interval from the first study drug dose to the first date a decline from Baseline in PSA level of 90% or greater was recorded. Time to PSA decline ≥ 90% was estimated using the Kaplan-Meier method. | From first dose until the EOS date of 27-Apr-2017; median duration of treatment of 1666.0 days (range of 52-2052) | 
| Time to PSA ≤ 4 ng/ml | Time to PSA ≤ 4 ng/ml is defined as the time interval from the first study drug dose to the first date a decline in PSA to a result of 4 ng/ml or below was recorded. Time to PSA ≤ 4 ng/ml was estimated using the Kaplan-Meier method. | From first dose until the EOS date of 27-Apr-2017; median duration of treatment of 1666.0 days (range of 52-2052) | 
| Time to PSA ≤ 0.1 ng/ml | Time to PSA ≤ 0.1 ng/ml is defined as the time interval from the first study drug dose to the first date a decline in PSA to a result of 0.1 ng/ml or below was recorded. Time to PSA ≤ 0.1 ng/ml was estimated using the Kaplan-Meier method. | From first dose until the EOS date of 27-Apr-2017; median duration of treatment of 1666.0 days (range of 52-2052) | 
| Time to PSA Progression | Time to PSA progression is defined as the time interval from the first study drug dose to the first date of PSA progression. PSA progression is defined as a ≥ 25% increase in PSA with an absolute increase of ≥ 2 ng/mL above the nadir unless the PSA next measurement(s), if available, does not confirm the PSA progression. | From first dose until the EOS date of 27-Apr-2017; median duration of treatment of 1666.0 days (range of 52-2052) | 
| PSA Doubling Time | PSA doubling time was to be calculated from the slope estimated from a linear regression of the natural log of PSA fitted on time, if the slope was positive. Since the slope was negative for all participants, PSA doubling time could not be calculated. | From Baseline to Week 25 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bone turnover, hormone-naïve, prostate specific antigen, Prostate Cancer