a study to determine the short-term safety of continuous dosing of abiraterone acetate and prednisone in modified fasting and fed states to patients with metastatic castration-resistant prostate cancer

Conditions: Prostate Neoplasms; Prostate Cancer

Summary: the purpose of this study is to establish the safety profile of oral (by mouth) abiraterone acetate and oral prednisone following short-term administration after standardized low-fat or high-fat meals to patients with metastatic (spreading) castration-resistant prostate cancer (mcrpc).

this is a multicenter, open-label study of 24 (up to a total of 28) men to assess the short-term safety of oral abiraterone acetate 1 g and oral prednisone 5 mg twice daily administered in the modified fasted state and after meals of various fat contents. all patients will take daily abiraterone acetate for the first 7 days in the modified fasted state (no food for 2 hours before and 1 hour after the dose). in cohort 1, up to 6 evaluable patients will take abiraterone acetate daily for 7 days after a standardized low-fat meal from cycle 1 day 8 to cycle 1 day 14; or, in cohort 2, up to 6 evaluable patients will take abiraterone acetate daily for 7 days after a standardized high-fat meal from cycle 1 day 8 to cycle 1 day 14. all patients will then continue to take abiraterone acetate daily in the modified fasted state starting on cycle 1 day 15 until disease progression. toxicity related to dosing after the low-fat or high-fat meals is defined as grade 3 or higher aes of special interest; or grade 3 or higher serious adverse events (saes) that occur during the food safety evaluation period. cohort 2 may be expanded to a total of 18 evaluable patients if deemed to be safe. decisions regarding the escalation of cohort or expansion of cohorts will be made by a study evaluation team. pharmacokinetic evaluation for each cohort will be performed on cycle 1 days 7 and 14 at predose and multiple timepoints postdose over 24 hours; cycle 1 days 8 and 11 at 2 hours following abiraterone acetate dose administration. abiraterone acetate, 1 g (four 250-mg tablets) orally (taken by mouth) once daily. patients may take abiraterone acetate until progression of clinical disease. prednisone, 5 mg, orally, twice a day.

Eligibility criteria:
inclusion criteria: * adenocarcinoma of the prostate * metastatic disease documented by bone, computed tomography (ct) or magnetic resonance imaging (mri) scan * surgical or medical castration with testosterone less than 50 ng/dl (\< 2.0 nm) * prostate-specific antigen (psa) or radiographic progression documented by assessments specified in study protocol * platelets \>100,000/µl * hemoglobin \>=9.0 g/dl * liver function tests (lfts): serum bilirubin \< 1.5 x uln; ast or alt \< 2.5 x uln; eastern cooperative oncology group (ecog) status score of \<=2 exclusion criteria: * small cell carcinoma of the prostate * known brain metastasis, chronic liver disease with elevated lfts * prior cytotoxic chemotherapy for metastatic prostate cancer * treatment of prostate cancer within 30 days of day 1 cycle 1 with surgery, radiation, chemotherapy or immunotherapy * use of investigational drug within 30 days of day 1 cycle 1 or current enrollment in an investigational drug or device study * recent history of ischemic heart disease, electrocardiogram (ecg) abnormalities or atrial fibrillation * active infection or other medical condition that would make prednisone (corticosteroid) use contraindicated * chronic medical condition requiring a higher dose of corticosteroid than prednisone 5 mg twice daily

Keywords: metastatic castration-resistant prostate cancer crpc abiraterone acetate prednisone food safety