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

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)

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.

Study Overview

• Status: Terminated
• Conditions: Recurrent Prostate Cancer; Hormone-resistant Prostate Cancer; Adenocarcinoma of the Prostate; Stage IV Prostate Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: questionnaire administration; Other: pharmacological study; Drug: abiraterone acetate; Dietary supplement: dietary intervention; Dietary supplement: dietary intervention

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU Knight Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (abiraterone acetate, low then high fat breakfast); 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.	Other: laboratory biomarker analysis; Correlative studies; Other: questionnaire administration; Ancillary studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Drug: abiraterone acetate; Given PO; Other Names: Zytiga; CB7630; Dietary supplement: dietary intervention; Receive low fat breakfast; Other Names: Dietary Modification; intervention, dietary; Dietary supplement: dietary intervention; Receive high fat breakfast; Other Names: Dietary Modification; intervention, dietary
Experimental: Arm II (abiraterone acetate, high then low fat breakfast); 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.	Other: laboratory biomarker analysis; Correlative studies; Other: questionnaire administration; Ancillary studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Drug: abiraterone acetate; Given PO; Other Names: Zytiga; CB7630; Dietary supplement: dietary intervention; Receive low fat breakfast; Other Names: Dietary Modification; intervention, dietary; Dietary supplement: dietary intervention; Receive high fat breakfast; Other Names: Dietary Modification; intervention, dietary

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

Collaborators and Investigators

• Sponsor: OHSU Knight Cancer Institute
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: July 29, 2013
• First Submitted That Met QC Criteria: July 29, 2013
• First Posted (Estimate): July 31, 2013

Study Record Updates

• Last Update Posted (Actual): April 28, 2017
• Last Update Submitted That Met QC Criteria: April 26, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Steroid Synthesis Inhibitors; Abiraterone Acetate
• Other Study ID Numbers: 9130 (Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium); P30CA069533 (U.S. NIH Grant/Contract); NCI-2013-01223 (Registry Identifier: CTRP (Clinical Trial Reporting Program))