Abiraterone Acetate Trial in African American Prostate Cancer Patients

Study Overview
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Brief Summary
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This is a pilot study of abiraterone acetate in African American/Black patients with castration-resistant prostate cancer. The primary objective is to determine the correlation between germline polymorphisms and antitumor activity (as defined by a decline in PSA of ≥ 30%) in African American patients with castration-resistant prostate cancer treated with abiraterone acetate. Patients will receive abiraterone acetate until the time of disease progression, in the absence of prohibitive toxicities. Patients will be followed for disease progression and survival.

Official Title
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A Pilot Study of Abiraterone Acetate in African American/Black Patients With Castration Resistant Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Abiraterone Acetate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. 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 Be willing/able to adhere to the prohibitions and restrictions specified in this protocol Written Authorization for Use and Release of Health and Research Study Information African American or Black (by self identification) Male aged 18 years and above Histologically or cytologically confirmed adenocarcinoma of the prostate Metastatic disease documented by standard imaging Progressive prostate cancer based on either rising PSA, new bone metastases, or progression of measurable disease according to PCWG2 12 guidelines. Patients in either of the following clinical states will be eligible for enrollment: i. No prior chemotherapy; ii. Patients previously treated with 1-2 prior chemotherapy regimens permitted, one of which must have been included docetaxel Surgically or medically castrated, with testosterone levels of < 50 ng/dl. Patients previously treated with an anti-androgen must demonstrate progression off of the anti-androgen. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2 Have a baseline serum potassium of ≥ 3.5 mEq/L Have aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin levels < 1.5 x ULN Have a serum albumin of ≥ 3.0 g/dL Total bilirubin ≤ 1.5 x ULN Have a platelet count of ≥ 100,000/μL Have an absolute neutrophil count of > 1500 cell/mm3 Have a calculated creatinine clearance ≥ 60 mL/min Have a hemoglobin of ≥ 9.0 g/dL Able to swallow the study drug as a whole 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 during the study and for 1 week after last dose of abiraterone acetate Exclusion Criteria: Active infection or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated Known brain metastasis Uncontrolled hypertension (systolic 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 III-IV heart disease or cardiac ejection fraction measurement of < 50% at baseline Administration of an investigational therapeutic within 30 days of screening Have 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 Have poorly controlled diabetes Have a history of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study agents Have a pre-existing condition that warrants long-term corticosteroid use in excess of study dose Have known allergies, hypersensitivity, or intolerance to abiraterone acetate or prednisone or their excipients

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abiraterone Acetate<br>Abiraterone acetate 1000mg orally daily until the time of disease progression, in the absence of prohibitive toxicities. | Drug: Abiraterone Acetate<br>* Abiraterone acetate 1000 mg orally daily (supplied as four 250 mg tablets) and prednisone 5 mg orally twice daily<br>* Other names: Zytiga;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With ≥ 30% Change in PSA | The primary objective of this study is to determine a correlation between inherited genetic polymorphisms and antitumor activity (as defined by a decline in PSA of ≥ 30%) in AA patients with castration-resistant prostate cancer treated with Abiraterone. The primary endpoint is the percent change in PSA from baseline to 12 weeks. A decline of ≥ 30% will be correlated with germline SNPs. | baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Assessment | Post-treatment changes in measurable disease by RECIST - Response Evaluation Criteria in Solid Tumors Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions | up to 12 weeks | 
| Time to Progression | post-treatment changes in measurable disease by time to disease progression (as per PCWG2 guidelines) | up to 12 weeks | 
| Bone Scan | post-treatment changes in bone scans (as per PCWG2 guidelines) (no new lesions versus new lesions.) | up to 12 weeks | 
| Safety of Abiraterone | To determine the safety of abiraterone Adverse events as defined by CTCAE v4. Number of participants with serious adverse events grade 4 or 5 | up to 12 weeks | 
| Testosterone | Post-treatment changes in testosterone | up to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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African American men, metastatic prostate cancer, castration resistant