Pharmacokinetic food-effect study of abiraterone acetate (AA) in patients with metastatic castration resistant prostate cancer (mCRPC): The ABIFOOD trial (EudraCt number: 2012-003226-25).

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Abstract
227 Background: A.A has been approved for the treatment of mCRPC before and after docetaxel. The standard regime consists on daily A.A. 1.000 mg in a fasting state along with prednisone 10mg q.d. However, data from pharmacokinetic (PK) studies in patients (pts) and healthy volunteers has revealed a significant food-effect with up to 7-10 folder increase in area under plasma concentration-time curve (AUC) when A.A is given with food, specially with fat content, [Chi KN, J Clin Pharmacol 2015]. Methods: ABIFOOD is a phase I, randomized trial to evaluate the short and long-term effect of diet on the PKs of A.A. in pts with mCRPC who have progressed to docetaxel. Eligible pts include men ≥ 18 years old with mCRPC, ECOG performance status (PS) < 2 and an adequate organ function. Pts are randomly assigned to receive 4-weekly cycles of 250 mg A.A with standard meal (Arm A), 250 mg A.A with high-fat meal (Arm B) or 1000 mg A.A in fasting conditions (Arm C). PK analyses are conducted at week 1 (W1) and cycle 5. Results: Fifteen pts (5, 3 and 7 in arms A, B and C respectively) have been included and 6 are still on treatment. Median age is 72, 97% have ECOG-PS 1. Gleason Score is > 8 in 6 (40%) pts.Geometric mean abiraterone [AUC (ng.h/ml) (IQR)] at W1 did not significantly differ between treatment arms [arm A: 404.68 (368.4 - 488.2), arm B: 372 (334.6 - 440.5) arm C: 656.51 (387.8 – 1144.5) p 0.15]. PK data did not influence activity or toxicity. Progression free survival was 8.50, 6.33 and 4.86 months in Arms A, B and C respectively (p 0.53). One patient in arm A is still on treatment after 17 cycles. Conclusions: The administration of lower doses of A.A with food [regardless the fat content], might achieve comparable plasma levels to standard dosing with no detriment in efficacy or toxicity parameters. The study is actively recruiting and data on additional pts and long term PK parameters will be presented. Clinical trial information: EudraCt number: 2012-003226-25.