A Study to Evaluate Serum Testosterone Levels in Patients With Metastatic Castration-Resistant Prostate Cancer

This was a 12-week, open-label study of abiraterone acetate in at least 50 patients with metastatic castration-resistant prostate cancer.

Inclusion criteria

• Written informed consent obtained prior to any study-related procedure being performed
• Male subjects at least 18 years of age or older at time of consent
• Pathologically confirmed adenocarcinoma of the prostate
• Ongoing therapy with a GnRH agonist or antagonist AND serum testosterone level <50 ng/dL at screening
• Metastatic disease documented by computed tomography (CT)/ magnetic resonance imaging (MRI) or bone scan. Imaging obtained within 42 days prior to the start of study medication will be accepted.
• Meeting disease progression according to the recommendations of the prostate cancer working group 2 by one of the following criteria:

• Two rises of PSA (taken a minimum of 1 week apart) from a baseline measurement of at least 2 ng/mL,
• Imaging progression (CT/MRI) by RECIST criteria
• Nuclear scan progression by new lesion.
• Discontinuation of flutamide or nilutamide, and other anti-androgens at least 4 weeks prior to the start of study medication; discontinuation of bicalutamide at least 6 weeks prior to start of study medication.
• Discontinuation of Radiotherapy > 4 weeks prior to start of study medication.
• ECOG performance status of 0-1 at screening
• Screening blood counts of the following:

• Absolute neutrophil count > 1500/µL
• Platelets > 100,000/µL
• Hemoglobin > 9 g/dL
• Screening chemistry values of the following:

• ALT and AST < 2.5 x ULN
• Total bilirubin < 1.5 x ULN
• Creatinine< 1.5 x ULN
• Albumin > 3.0 g/dL
• Potassium > 3.5 mmol/L
• Life expectancy of at least 6 months at screening
• Subject is willing and able to comply with all protocol requirements assessments
• Agrees to protocol-defined use of effective contraception.

Exclusion criteria

• History of impaired pituitary or adrenal gland function
• Prior therapy with abiraterone acetate, orteronel, ketoconazole or any other CYP17 inhibitor
• Prior therapy with enzalutamide
• Prior use of experimental androgen receptor antagonist
• Previous exposure to Ra-223:Xofigo
• Previous chemotherapy
• Initiation of bisphosphonate or denosumab therapy within 30 days prior to the start of study medication. Patients who are on a stable dose of these medications for at least 30 days at the time of starting study drug are eligible.
• Therapy with estrogen within 30 days prior to the start of study medication
• Use of systemic glucocorticoids equivalent to > 10 mg of prednisone daily; patients who have discontinued or have reduced dose to < 10 mg prednisone within 14 days prior to the start of study medication will be eligible
• Prior use of any herbal products that may decrease PSA levels (eg., saw palmetto) within 30 days of start of study medication
• Known metastases to the brain or CNS involvement
• History of other malignancy within the previous 2 years
• Major surgery within 30 days prior to the start of study medication
• Blood transfusion within 30 days of screening
• Serious, persistent infection within 14 days of the start of study medication
• Persistent pain that requires the use of a narcotic analgesic
• Known gastrointestinal disease or condition that may impair absorption
• Treatment with any investigational drug within 4 weeks prior to Day -1 of the study.
• Known history of human immunodeficiency virus (HIV) or seropositive test for hepatitis C virus or hepatitis B virus
• Have poorly controlled diabetes.
• Uncontrolled hypertension
• History of New York Heart Association (NYHA) class III or IV heart failure
• Serious concurrent illness, including psychiatric illness, that would interfere with study participation
• Inability to swallow tablets whole
• Known hypersensitivity to any excipients in study medications
• Moderate to severe hepatic impairment (Child-Pugh Classes B and C)