Trial Information

A Phase 1b Safety Study of Abiraterone Acetate (JNJ-212082) and Docetaxel in Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

This is an open-label (patients and their doctors will know the identity of study drug
administered), uncontrolled (patients are not assigned to treatment by chance), multicenter
safety study of escalating dose levels of abiraterone acetate administered in combination
with docetaxel plus prednisone in patients with metastatic castration-resistant prostate
cancer (mCRPC). This study is conducted in 2 parts. Part I consists of Screening, Treatment,
assessment of dose-limiting toxicity (DLT), and determination of the maximum tolerated dose
(MTD). Participants are enrolled in sequential 6-subject cohorts (groups) and administered
combination therapy (abiraterone acetate and docetaxel plus prednisone) according to a
dose-escalation schedule. The abiraterone acetate dose in this study will escalate from 500
mg to 1000 mg daily until the MTD is determined. The MTD is the highest combination dose
among the dose combinations investigated in this study at which no more than 2 (33%) of the
patients in a cohort experience a DLT. A DLT is defined by an adverse event occurring from
Day 1 Week 2 (first dose of abiraterone acetate) to the day before the Day 1 Week 7
docetaxel infusion (3 weeks after the second docetaxel infusion); non-hematological toxicity
>=Grade 3; Grade 4 neutropenia lasting more than 5 days, neutropenia complicated by fever,
or systemic infection; thrombocytopenia <25,000/mcL, or any thrombocytopenia requiring
platelet transfusion; and, any subjectively intolerable toxicity. Part II of the study
consists of Continuing Treatment, when patients remain at the allocated dose level, escalate
to the combination MTD, or discontinuation of docetaxel (if toxicity or intolerability
develops) and continue abiraterone acetate (up to 1000 mg/day) plus prednisone, until
disease progression; End of Treatment, when posttreatment efficacy and safety will be
documented; and Follow-Up, when survival status and new antitumor therapy are monitored.
Blood samples for pharmacokinetic and efficacy measurements will be collected at selected
times during the study. Safety will be monitored. The total duration of study participation
may be up to 36 months. Oral abiraterone acetate will be administered as a single daily dose
(500, 750, or 1000 mg). Docetaxel will be administered once every 3 weeks as an intravenous
(IV) infusion (60 or 75 mg/m2) over 1 hour. Study participants will premedicate with oral
dexamethasone 8 mg 1, 3, and 12 hours before the start of each docetaxel IV infusion. Oral
prednisone 5 mg will be administered twice daily.