Abiraterone Race in Metastatic Castrate-resistant Prostate Cancer

Study Overview
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Brief Summary
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The primary goal is to prospectively estimate the median radiographic PFS of African American and Caucasian men with mCRPC to abiraterone acetate and prednisone.

Detailed Description
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This is a non-comparative pilot open-label, parallel arm, multicenter study of abiraterone acetate in African American and Caucasian men with mCRPC. Patients will self-report on race and 50 patients will be enrolled into each group. Patients will be treated on open-label treatment until evidence of disease progression as defined by Prostate Cancer Working Group Two (PCWG2) definition or until two years at which point they will roll over to the standard of care at that time. The study agent abiraterone acetate will be administered by the patient at a dose of 1000mg orally once daily with prednisone 5 mg BID in 4-week cycles throughout the treatment period.

Official Title
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A Phase II Open-label, Parallel Group Study of Abiraterone Acetate Plus Prednisone in African American and Caucasian Men With Metastatic Castrate-resistant Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Abiraterone acetate
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male, age ≥ 18 years Karnofsky performance status ≥ 70 Life expectancy of ≥ 12 months 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, and should be able to swallow tablets whole, without crushing/chewing tablets 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 Adequate laboratory parameters Histologically confirmed diagnosis of adenocarcinoma of the prostate. Histologic variants of prostate cancer, including neuroendocrine features and small cell carcinoma of the prostate are excluded Radiographic evidence of metastatic disease; evaluable non-target lesions and/or bone only metastasis are permitted Ongoing ADT using an LHRH agonist (e.g. leuprolide, goserelin) or antagonist (e.g. degarelix) must continue on therapy unless prior bilateral orchiectomy has been performed. Screening serum testosterone must be <50 ng/dl PSA ≥ 2.0 ng/mL Evidence of of castration resistant disease on ADT as evidenced by one of the following: Absolute rise in PSA of 2.0 ng/mL or greater, minimum 2 consecutive rising PSA levels with an interval of ≥ 1 week between each PSA level, OR 2 consecutive PSA levels 50% or greater above the PSA nadir achieved on ADT and separated at least 1 week apart, OR CT or MRI based evidence of disease progression (soft tissue, nodal or visceral disease progression) according to modified PCWG2 criteria or modified RECIST 1.1 criteria, or at least 1 new bone scan lesion as compared to the most immediate prior radiologic studies) A minimum of 2 weeks elapsed off of antiandrogen therapy prior to start of study drug (i.e. flutamide, nilutamide, bicalutamide) A minimum of 4 weeks elapsed off of sipuleucel-T prior to start of study drug A minimum of 4 weeks from any major surgery prior to start of study drug Self-reported race of either African American or Caucasian Ability to swallow, retain, and absorb oral medication Exclusion Criteria: Prior treatment with abiraterone acetate or enzalutamide Active infection or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated Any chronic medical condition requiring a higher dose of corticosteroid than 5mg prednisone/prednisolone bid Have known allergies, hypersensitivity, or intolerance to abiraterone acetate or prednisone or their excipients Pathological finding consistent with small cell carcinoma of the prostate Symptomatic Liver or visceral organ metastasis Have a history of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study agents Known brain metastasis Prior cytotoxic chemotherapy or biologic therapy for the treatment of CRPC Previously treated with ketoconazole for prostate cancer for greater than 7 days Prior systemic treatment with an azole drug (e.g. fluconazole, itraconazole) within 4 weeks of Cycle 1, Day 1 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. Poorly controlled diabetes 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 therapy Other malignancy, except non-melanoma skin cancer, with a ≥ 30% probability of recurrence within 24 months Administration of an investigational therapeutic within 30 days of Cycle 1, Day 1 Any condition which, in the opinion of the investigator, would preclude participation in this trial

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 and Prednisone<br>abiraterone acetate will be administered by the patient at a dose of 1000mg orally once daily with prednisone 5 mg BID in 4-week cycles | Drug: Abiraterone acetate<br> <br> * Other names: Zytiga;Drug: Prednisone<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Radiographic Progression Free Survival (PFS) | Time in months from the start of study treatment to the date of first progression according to Prostate Cancer Working Group 2 criteria, or to death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median rPFS was estimated using a Kaplan-Meier curve. | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PSA Response | Percent of men with Prostate Specific Antigen (PSA) declines > 30%, > 50% and > 90% | Baseline and up to 2 years | 
| Median Time to PSA Progression | Time to PSA progression as defined by PCWG 2 criteria is the date that a 25% or greater increase and an absolute increase of 2 ng/mL or more from the nadir is documented, which is confirmed by a second value obtained 3 or more weeks later. | up to 2 years | 
| Number of Men With PSA Decline to < 0.1 and < 0.2 ng/ml | Number of men who achieve a PSA decline to < 0.1 and < 0.2 ng/ml | up to 2 years | 
| Percent of Subjects Experiencing Hypertension | Incidence and grade of hypertension in the two populations. (Grade 1: Systolic BP 120 to 139 mmHg or diastolic BP 80 to 89 mmHg, Grade 2: Systolic BP 140 to 159 mmHg or diastolic BP 90 to 99 mmHg, Grade 3: Systolic BP ≥160 mmHg or diastolic BP ≥100 mmHg, Grade 4: Life-threatening consequences, urgent intervention indicated) | up to 2 years | 
| Overall Survival | Length of patient's life after starting study | up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate cancer, metastatic, castrate resistant, abiraterone acetate, prednisone, metastatic prostate cancer