Abiraterone Acetate in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

Open Label Pharmacodynamic Study of Abiraterone Acetate in the Treatment of Metastatic, Castration Resistant Prostate Cancer

This phase II trial studies how well abiraterone acetate works in treating patients with hormone-resistant prostate cancer that has spread from the primary site (place where it started) to other places in the body (metastatic). Abiraterone acetate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To determine the magnitude of tissue testosterone suppression by abiraterone acetate in metastatic castrate-resistant prostate cancer (CRPC) (resistant to luteinizing hormone-releasing hormone [LHRH] agonist or orchiectomy ± antiandrogen) after one month of treatment to establish tissue based mechanism of action.

OUTLINE:

Patients receive abiraterone acetate orally once daily and prednisone twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Inclusion Criteria:

• Have signed an informed consent document indicating that the subjects understands the purpose of and procedures required for the study and are willing to participate in the study

• Written authorization for use and release of health and research study information has been obtained

• Be willing/able to adhere to the prohibitions and restrictions specified in this protocol

• Able to swallow the study drug whole as a tablet

• Willing to take abiraterone acetate on an empty stomach; no food should be consumed at least two hours before and for at least one hour after the dose of abiraterone acetate is taken

• Patients who have partners of childbearing potential must be willing to use a method of birth control with adequate barrier protection as determined to be acceptable by the principal investigator and sponsor during the study and for 1 week after last dose of abiraterone acetate

• Histologically proven adenocarcinoma of the prostate

• Eastern Cooperative Oncology Group (ECOG) performance status =< 2

• Metastatic castration resistant prostate cancer as defined by serum testosterone < 50 ng/ml and one of the following:

  • Prostate specific antigen (PSA) level of at least 2 ng/ml that has risen on at least 2 successive occasions at least 1 week apart
  • Evaluable disease progression by modified RECIST (Response Evaluation Criteria in Solid Tumors)
  • Progression of metastatic bone disease on bone scan with > 2 new lesions

• Maintenance of Lupron or antagonist unless previously treated with orchiectomy

• The presence of metastatic disease amenable to computed tomography (CT) or ultrasound guided biopsy; this may include thoracolumbar vertebral bodies, pelvis, femur or humerus, or soft tissue or nodal metastasis amenable to biopsy (excluding lung or pleural lesions)

• Patients may have received secondary hormonal manipulations (excluding prior abiraterone acetate, MDV3100 or TAK700) or up to two lines of chemotherapy; all prior therapy except Lupron must have been discontinued for more than 4 weeks before enrollment

• Serum potassium of >= 3.5 mEq/L

• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) < 1.5 x upper limit of normal (ULN)

• Bilirubin levels < 1.5 x ULN

• Serum albumin of >= 3.0 g/dL

• Total bilirubin =< 1.5 x ULN

• Calculated creatinine clearance >= 60 mL/min

• Platelet count of >= 100,000/uL

• Absolute neutrophil count of > 1,500 cell/mm^3

• Hemoglobin >= 9.0 g/dL

Exclusion Criteria:

• Active infection or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated
• Patients who are currently receiving active therapy for other neoplastic disorders will not be eligible
• Patients with histologic evidence of small cell carcinoma of the prostate will not be eligible
• Known brain metastasis
• Uncontrolled hypertension (systolic blood pressure [BP] >= 160 mmHg or diastolic BP >= 95 mmHg); patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment
• 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 II-IV heart disease or cardiac ejection fraction measurement of < 50 % at baseline
• Atrial fibrillation, or other cardiac arrhythmia requiring medical therapy
• Administration of an investigational therapeutic within 30 days of screening
• Patients with dementia/psychiatric illness/social situations that would limit compliance with study requirements or would prohibit the understanding and/or giving of informed consent will not be eligible
• Patients with any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements
• Patients requiring therapeutic anticoagulation (e.g., warfarin, dabigatran, heparin, or low molecular weight heparins [Lovenox, dalteparin])
• Patients with poorly controlled diabetes
• Patients with a history of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study agents
• Patients with a pre-existing condition that warrants long-term corticosteroid use in excess of study dose
• Patients with known allergies, hypersensitivity, or intolerance to abiraterone acetate or prednisone or their excipients
• Child-Pugh class B or C hepatic impairment