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

Phase 1
Terminated
Conditions
Recurrent Prostate Cancer
Adenocarcinoma of the Prostate
Hormone-resistant Prostate Cancer
Stage IV Prostate Cancer
Interventions
Dietary Supplement: dietary intervention
Other: pharmacological study
Other: questionnaire administration
Other: laboratory biomarker analysis
Registration Number
NCT01913015
Lead Sponsor
OHSU Knight Cancer Institute
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.

Recruitment & Eligibility

Status
TERMINATED
Sex
Male
Target Recruitment
3
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 & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Arm I (abiraterone acetate, low then high fat breakfast)questionnaire administrationPatients 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.
Arm I (abiraterone acetate, low then high fat breakfast)pharmacological studyPatients 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.
Arm II (abiraterone acetate, high then low fat breakfast)dietary interventionPatients receive abiraterone acetate as in Arm I. Patients eat a high fat breakfast on day 3, and a low fat breakfast on day 10.
Arm II (abiraterone acetate, high then low fat breakfast)questionnaire administrationPatients receive abiraterone acetate as in Arm I. Patients eat a high fat breakfast on day 3, and a low fat breakfast on day 10.
Arm II (abiraterone acetate, high then low fat breakfast)pharmacological studyPatients receive abiraterone acetate as in Arm I. Patients eat a high fat breakfast on day 3, and a low fat breakfast on day 10.
Arm I (abiraterone acetate, low then high fat breakfast)dietary interventionPatients 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.
Arm I (abiraterone acetate, low then high fat breakfast)laboratory biomarker analysisPatients 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.
Arm II (abiraterone acetate, high then low fat breakfast)laboratory biomarker analysisPatients receive abiraterone acetate as in Arm I. Patients eat a high fat breakfast on day 3, and a low fat breakfast on day 10.
Arm I (abiraterone acetate, low then high fat breakfast)abiraterone acetatePatients 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.
Arm II (abiraterone acetate, high then low fat breakfast)abiraterone acetatePatients receive abiraterone acetate as in Arm I. Patients eat a high fat breakfast on day 3, and a low fat breakfast on day 10.
Primary Outcome Measures
NameTimeMethod
Area under the curve (AUC)0-24 measurementUp to 24 hours (day 1)

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.

Secondary Outcome Measures
NameTimeMethod
Accuracy of patient-collected DBS sampling techniqueDay 3

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.

Patient adherence to pre-defined sampling scheduleUp to day 14

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.

Patient satisfaction of DBS method, measured using the Patient Questionnaire of DBS Sampling MethodDay 14

Paired t-test will be conducted to compare the DBC (or transformed DBC) for the evaluation of carry-over effect.

Trial Locations

Locations (1)

OHSU Knight Cancer Institute

🇺🇸

Portland, Oregon, United States

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