a drug-drug interaction study of abiraterone acetate plus prednisone with dextromethorphan and theophylline in patients with metastatic castration-resistant prostate cancer

Conditions: Prostate Neoplasms

Summary: the purpose of this study is to evaluate the effects of multiple doses of abiraterone acetate plus prednisone on the pharmacokinetics (study of what the body does to a drug) of single doses of dextromethorphan hydrobromide and theophylline in patients with castration resistant prostate cancer.

this is an open-label (identity of assigned study drug will be known) study of abiraterone acetate plus prednisone in male patients with metastatic castration-resistant prostate cancer. this study will consist of screening, treatment, and follow-up periods, and will have 2 study groups. patients in group a and b will receive daily abiraterone acetate (1000 mg) plus prednisone (5 mg) twice daily beginning on cycle 1 day 1 until disease progression. patients in group a will take dextromethorphan hydrobromide 30 mg administered orally once daily on day -8 and day 8 of cycle 1. patients in group b will take theophylline 100 mg administered orally once daily on day -8 and day 8 of cycle 1. serial pharmacokinetic samples will be collected and safety will be monitored throughout the study.

Eligibility criteria:
inclusion criteria: * histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology * documented metastatic disease * documented prostate specific antigen (psa) progression according to prostate cancer working group 2 criteria, with psa value \>=2 ng/ml despite medical or surgical castration, or prostate cancer progression documented by radiographic progression according to response evaluation criteria in solid tumors criteria * surgically or medically castrated with testosterone levels of \<50 ng/dl * eastern cooperative oncology group (ecog) performance status of \<=2 * group a only: genomic testing at screening indicating cyp2d6 extensive metabolizer status * protocol-defined laboratory values exclusion criteria: * serious or uncontrolled co-existent non-malignant disease, including active and uncontrolled infection * group a only: genomic testing at screening indicating cyp2d6 non-extensive metabolizer status, or prior treatment with dextromethorphan-containing medication or any medication that is a strong inhibitor or inducer of cyp2d6 within 5 half-lives of that drug or 7 days, whichever is longer, prior to cycle 1 day -8 * group b only: prior treatment with theophylline or any medication that is a strong inhibitor or inducer of cyp1a2 within 5 half-lives of that drug or 7 days, whichever is longer, prior to cycle 1 day -8 * abnormal liver function * uncontrolled hypertension (repeated systolic blood pressure \>=160 mmhg, or diastolic blood pressure \>=95 mmhg) * active or symptomatic viral hepatitis or chronic liver disease * known brain metastasis * history of pituitary or adrenal dysfunction * clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or new york heart association class iii or iv heart disease or cardiac ejection fraction measurement of \<50% at baseline * history of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug * surgery or local prostatic intervention within 28 days of the first dose, and any clinically relevant sequelae from the surgery must have resolved prior to cycle 1 day 1 * radiotherapy or immunotherapy within 28 days, or single fraction of palliative radiotherapy within 14 days of administration of cycle 1 day 1 * any acute toxicities due to prior therapy that have not resolved * current enrollment in an investigational drug or device study or participation in such a study within 28 days of cycle 1 day 1 * previous abiraterone acetate or other investigational cyp17 inhibitor (eg, tak-700)

Keywords: prostate neoplasms metastatic castration resistant prostate cancer metastatic castration refractory prostate cancer prostate cancer abiraterone acetate cb7630