Dietary Fat Levels and Abiraterone Acetate Uptake in Patients With Metastatic Hormone-Resistant Prostate Cancer

Study Overview
=================
Brief Summary
-----------------
This randomized pilot phase I trial studies the side effects of dietary fat levels and abiraterone acetate uptake in patients with metastatic hormone-resistant prostate cancer. Abiraterone acetate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Eating a low or high fat diet may increase the uptake of abiraterone acetate.

Detailed Description
-----------------
PRIMARY OBJECTIVES: I. To assess the dietary effects of a low fat and high fat diet at a low abiraterone acetate dose (250 mg) on drug levels compared to standard dose administered in a fasting condition. SECONDARY OBJECTIVES: I. To potentially guide decisions in the future to use low dose abiraterone in a fed state and decrease overall cost. II. To evaluate the potential relationship between esterase activity and abiraterone metabolism in an exploratory analysis. III. To determine the feasibility of using patient-collected dried blood spot (DBS) samples for pharmacokinetic monitoring. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive standard dose abiraterone acetate orally (PO) once daily (QD) (held on days 2, 3, 9, and 10), and low-dose abiraterone acetate PO QD on days 3 and 10. Patients eat a low fat breakfast on day 3 and a high fat breakfast on day 10. ARM II: Patients receive abiraterone acetate as in Arm I. Patients eat a high fat breakfast on day 3, and a low fat breakfast on day 10.

Official Title
-----------------
An Open-Label, Phase I, Randomized Pharmacokinetic Study of Dietary Effects on Abiraterone Acetate Drug Levels in Patients With Metastatic Castration-Resistant Prostate Cancer (DEAL)

Conditions
-----------------
Recurrent Prostate Cancer, Adenocarcinoma of the Prostate, Stage IV Prostate Cancer, Hormone-resistant Prostate Cancer

Intervention / Treatment
-----------------
* Drug: abiraterone acetate
* Dietary Supplement: dietary intervention
* Dietary Supplement: dietary intervention
* Other: pharmacological study
* Other: questionnaire administration
* Other: laboratory biomarker analysis


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed adenocarcinoma of the prostate About to initiate or currently being treated with abiraterone acetate 1000 mg orally once daily Clinically able to receive abiraterone acetate in the opinion of the investigator in accordance with standard prescribing practices Ability to consume a low fat and high fat diet Expected duration of continuous abiraterone therapy > 8 weeks Signed and dated informed consent Exclusion Criteria: Patients taking medications that strongly inhibit or induce cytochrome P450 (CYP)3A4 within 28 days prior to the start of the study will be excluded

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (abiraterone acetate, low then high fat breakfast)<br>Patients receive standard dose abiraterone acetate PO QD (held on days 2, 3, 9, and 10), and low-dose abiraterone acetate PO QD on days 3 and 10. Patients eat a low fat breakfast on day 3 and a high fat breakfast on day 10. | Drug: abiraterone acetate<br>* Given PO<br>* Other names: Zytiga;Dietary Supplement: dietary intervention<br>* Receive low fat breakfast<br>* Other names: intervention, dietary;Dietary Supplement: dietary intervention<br>* Receive high fat breakfast<br>* Other names: intervention, dietary;Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;Other: questionnaire administration<br>* Ancillary studies<br>Other: laboratory biomarker analysis<br>* Correlative studies<br>|
| Experimental: Arm II (abiraterone acetate, high then low fat breakfast)<br>Patients receive abiraterone acetate as in Arm I. Patients eat a high fat breakfast on day 3, and a low fat breakfast on day 10. | Drug: abiraterone acetate<br>* Given PO<br>* Other names: Zytiga;Dietary Supplement: dietary intervention<br>* Receive low fat breakfast<br>* Other names: intervention, dietary;Dietary Supplement: dietary intervention<br>* Receive high fat breakfast<br>* Other names: intervention, dietary;Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;Other: questionnaire administration<br>* Ancillary studies<br>Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve (AUC)0-24 measurement | The cross-over difference (log[AUC0-24(low fat)] - log[AUC0-24(high fat)]) of each patient will be computed and graphically illustrated. The cross-over difference will be estimated and reported with 95% confidence interval. Hills-Armitage approach will be used to adjust for the period effect for the estimation. In addition, a bioequivalence range will be computed for the log(AUC0-24[1000 mg with fasting food]), allowing for 20% differences in each side. | Up to 24 hours (day 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Accuracy of patient-collected DBS sampling technique | The first three patients enrolled will have duplicate venous blood samples obtained in clinic 2 hours post-dose for in vivo confirmation of the DBS methodology. | Day 3 | 
| Patient adherence to pre-defined sampling schedule | Patients will document the date/time of drug administration and the date/time of sample collection using a drug and DBS sample diary. Deviations greater than 10% of the shorter of the two time intervals surrounding the pre-defined time point will be considered non-adherent. Adherence rates will be compared for different time points. | Up to day 14 | 
| Patient satisfaction of DBS method, measured using the Patient Questionnaire of DBS Sampling Method | Paired t-test will be conducted to compare the DBC (or transformed DBC) for the evaluation of carry-over effect. | Day 14 |