Urokinase Plasminogen Activator Receptor in Abiraterone Treated Patients With Castration Resistant Prostate Cancer

uPAR in Blood From Zytiga® (Abiraterone) Treated Patients With Castration Resistant Prostate Cancer - a Predictive Marker of Response?

The purpose of this study is to investigate cleavage products of the urokinase plasminogenactivator receptor (uPAR) in plasma from patients with castration resistant prostate cancer as a predictive marker of response to abiraterone.

Inclusion Criteria:

• Signed informed consent.

• Age ≥18 years and male

• Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology

• Received at least one but not more than two cytotoxic chemotherapy regimens for metastatic CRPC. At least one regimen must have contained a taxane such as docetaxel.

• Prostate cancer progression as assessed by the investigator with one of the following:

  • PSA progression according to Prostate Cancer Working Group 2 (PCWG2) criteria
  • Solid Tumors (RECIST) criteria or bone scans with or without PSA progression.
  • Radiographic progression in soft tissue according to Response Evaluation Criteria in

• Ongoing androgen deprivation with serum testosterone <2.0 nM

• Eastern Cooperative Oncology Group (ECOG) performance status of ≤2

• Platelet count ≥100,000/μL

• Serum albumin ≥30 g/dL

• Serum creatinine <1.5 x upper limit of normal (ULN) or a calculated creatinine clearance ≥ 60 mL/min

• Serum potassium ≥3.5 mmol/L

Exclusion Criteria:

• Received abiraterone or MDV3100 in the past.

• Serious or uncontrolled co-existent non-malignant disease, including active and uncontrolled infection.

• Abnormal liver functions consisting of any of the following:

  • Serum bilirubin ≥1.5 x ULN (except for subjects with documented Gilbert's disease, for whom the upper limit of serum bilirubin is 51 µmol/l)
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2.5 x ULN

• Uncontrolled hypertension (systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥95 mmHg); subjects with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive therapy.

• Active or symptomatic viral hepatitis or chronic liver disease

• 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 (NYHA) Class III or IV heart disease or left ventricular ejection fraction (LVEF) of <50% at baseline.

• Known brain metastasis

• History of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study drug

• Any acute toxicities due to prior chemotherapy or radiotherapy that have not resolved to a NCI-CTCAE (Version 4.0) Grade of ≤1. Chemotherapy induced alopecia and Grade 2 peripheral neuropathy is allowed.

• Use of other anticancer therapy including cytotoxic, radionucleotide, and immunotherapy; diethylstilbestrol; PC-SPES; spironolactone (ie, ALDACTONE, SPIRONOL); and other preparations such as saw palmetto thought to have endocrine effects on prostate cancer, within 4 weeks of Cycle 1 Day 1

• Prior systemic treatment with an azole drug (eg, fluconazole, itraconazole, ketoconazole) within 4 weeks of Cycle 1 Day 1

• Current enrolment in an investigational drug or device study or participation in such a study within 30 days of Day 1

• Condition or situation which, in the investigator's opinion, may put the subjects at significant risk, may confound the study results, or may interfere significantly with subject's participation in the study.