Food Effect Study of Abiraterone Acetate for Treatment of Patients With Castration-Resistant Prostate Cancer

Study Overview
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Brief Summary
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This randomized phase II trial studies the best way to give abiraterone acetate in treating patients with castration-resistant prostate cancer. Abiraterone acetate is effective in treating castrate resistant prostate cancer and is taken in the fasting state. However, the body's absorption of abiraterone is increased with food intake. This study will test the whether a lower dose of abiraterone taken with food has a similar effect on prostate specific antigen (PSA) compared to full dose taken fasting.

Detailed Description
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PRIMARY OBJECTIVES: I. To compare the pharmacodynamic effect of reduced dose (250mg daily) abiraterone acetate in the prandial state (250mg-Fed) to the full, standard 1000mg daily dose in the fasting state (1000mg-Fasting) as assessed by change in serum prostate-specific antigen (PSA). SECONDARY OBJECTIVES: I. To evaluate the effect of prandial states on plasma levels and the intra-patient pharmacokinetic variability of abiraterone acetate. II. To evaluate the safety profile of reduced dose abiraterone acetate taken in the prandial state. III. To evaluate the pharmacodynamic effect of reduced dose abiraterone acetate in the prandial state as assessed by reduction in the extra-gonadal androgen dihydroepiadrosterone sulfate (DHEA-S) and dihydroepiandrostenedione (DHEA). IV. To evaluate the effect of prandial state on time to disease progression (Working group criteria). OUTLINE: Patients are randomized to one of two treatment arms. ARM I: Patients receive abiraterone acetate orally (PO) daily first thing in morning after an overnight fast of at least 8 hours. ARM II: Patients receive abiraterone acetate PO daily within 30 minutes of a conventional low-fat breakfast. In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Both arms will also be treated with prednisone 5mg twice daily. After completion of study treatment, patients are followed up within 30 days.

Official Title
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A Prospective Randomized Pilot Study Evaluating the Food Effect on the Pharmacokinetics and Pharmacodynamics of Abiraterone Acetate in Men With Castrate Resistant Prostate Cancer

Conditions
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Castration-resistant Prostate Cancer, Stage IV Prostate Cancer

Intervention / Treatment
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* Drug: abiraterone acetate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed prostate cancer with progressive disease defined as either: 2 or more new lesions on bone scan or Progressive disease on computed tomography (CT)/magnetic resonance imaging (MRI) according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria or Rising prostate-specific antigen (PSA): PSA evidence for progressive prostate cancer consists of a minimum PSA level of at least 2 ng/ml, which has subsequently risen on at least 2 successive occasions, at least 2 weeks apart Evidence of castration resistance defined as disease progression despite a testosterone level < 50 ng/dL (or surgical castration) Any prior therapy for castrate disease is acceptable except prior abiraterone, which is excluded; a minimum washout of 28 days for any other anticancer therapy prior to first dose of study drug is required Any other radiotherapy or radionuclide require 28-day washout prior to first dose of study drug Denosumab or zoledronic acid are allowed Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Total bilirubin =< 1.5 x the upper limit of normal Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Therapy with other hormonal therapy, including any dose of megestrol acetate (Megace), finasteride (Proscar), dutasteride (Avodart), or any herbal product known to decrease PSA levels (e.g., saw palmetto and PC-SPES), or any systemic corticosteroid (other than prednisone =< 10 mg/day) within 4 weeks prior to first dose of study drug Therapy with supplements or complementary medicines/botanicals within 4 weeks of first dose of study drug is excluded with the following exceptions: Conventional multivitamin supplements Selenium Lycopene Soy supplements Inability to swallow capsules or known gastrointestinal malabsorption History of other malignancies, with the exception of adequately treated non-melanoma skin cancer or adequately treated superficial bladder cancer or other solid tumors curatively treated with no evidence of disease for >= 5 years from enrollment Blood pressure that is not controlled despite > 2 oral agents (systolic blood pressure [SBP] > 160 and diastolic blood pressure [DBP] > 90 documented during the screening period with no subsequent blood pressure readings < 160/100) Serum potassium (K)+ < 3.5 mmoL/L on more than one reading within the screening period Serious intercurrent infections or non-malignant medical illnesses that are uncontrolled Active psychiatric illness/social situations that would limit compliance with protocol requirements New York Heart Association (NYHA) class II, NYHA class III, or IV congestive heart failure (any symptomatic heart failure) Concurrent therapy with strong inhibitors or inducers of Cytochrome P450 (CYP)3A4 due to concerning possible drug-drug interactions with abiraterone
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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I (fasting)<br>Patients receive abiraterone acetate PO daily first thing in morning after an overnight fast of at least 8 hours. | Drug: abiraterone acetate<br>* Given PO<br>* Other names: Zytiga;|
| Experimental: Arm II (fed)<br>Patients receive abiraterone acetate PO daily within 30 minutes of a conventional low-fat breakfast. | Drug: abiraterone acetate<br>* Given PO<br>* Other names: Zytiga;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PSA Level | Data were analyzed on a log scale: log(week 12) - log(baseline) = log ratio. Smaller (more negative) values indicate a better outcome. | From baseline to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | Time to PSA progression (25% increase from baseline), radiographic progression, or death. | Assessed up to 3 years | 
| Adrenal Androgen Production (DHEA-S) | Extragonadal serum adrogen | Cycle 4 (4 months) | 
| Number of Participants With Adverse Events (AEs) | Patients with grade 3 or higher AE (CTCAE Version 4.03) | Assessed up to 1 year | 
| Peak Plasma Concentration of Abiraterone | Analyzed on a log scale due to skewness of distribution | Up to 4 months |