Clinical Drug Experience Knowledgebase

Criteria

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)