A QT/QTc and Multi-Dose Pharmacokinetic Study of Abiraterone Acetate Plus Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine the effect of abiraterone acetate plus prednisone on the conduction of electric charges within the heart and to determine the blood levels of abiraterone acetate following administration in patients with metastatic castration-resistant prostate cancer.

Detailed Description
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This is an open-label (identity of assigned study drugs will be known) study to evaluate the effects of abiraterone acetate plus prednisone on the conduction of electric charges within the heart in male patients diagnosed with metastatic castration-resistant prostate cancer (a progressive form of prostate cancer that spreads to other parts of the body). At various time points outline in the protocol from Day -1 of Cycle 1 up to Day 2 of Cycle 2, patients will have electrocardiograms extracted from a 24 hour holter-monitor to evaluate the electrical activity of their heart. Efficacy will be assessed according to Prostate Cancer Working Group 2 and modified Response Evaluation Criteria In Solid Tumors criteria. Serial blood samples for pharmacokinetic analysis (how the drug concentrations change over time) will be collected and safety will be monitored throughout the study. Patients will take 1000 mg of abiraterone acetate once daily plus prednisone 5 mg twice daily orally (by mouth) until disease progression and will be followed up for up to 60 months.

Official Title
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A QT/QTc and Multi-dose PK Study of Abiraterone Acetate (CB7630) Plus Prednisone in Patients With Metastatic Castration- Resistant Prostate Cancer

Conditions
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Prostate Neoplasms

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: Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology Documented metastatic disease Has not received chemotherapy or has no more than one line of cytotoxic chemotherapy or biologic therapy for treatment of castration resistant prostate cancer (CRPC) Documented prostate specific antigen (PSA) progression as assessed by the investigator according to Prostate Cancer Working Group 2 (PCWG2) criteria despite medical or surgical castration, or prostate cancer progression documented by radiographic progression according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria Surgically or medically castrated with testosterone levels of <50 ng/dL (<2.0 nM) Eastern Cooperative Oncology Group (ECOG) Performance Status of <= 1 Agrees to protocol-defined use of effective contraception Protocol-specified laboratory parameters Exclusion Criteria: Serious or uncontrolled co-existent non-malignant disease, including active and uncontrolled infection Abnormal liver function Uncontrolled hypertension Active or symptomatic viral hepatitis or chronic liver disease Known brain metastasis 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 Diagnosis of cardiac arrhythmia Treatment with anti-arrhythmic drugs primarily for cardiac arrhythmia Abnormal electrocardiogram Other malignancy (except non-melanoma skin cancer, that is active or has a ≥ 30% probability of recurrence within 24 months) History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug Surgery or local prostatic intervention within 30 days of the first dose Radiotherapy or immunotherapy within 30 days, or single fraction of palliative radiotherapy within 14 days of administration of Cycle 1 Day 1 Any acute toxicities due to prior therapy that have not resolved to a NCI CTCAE (version 3.0) grade of <=1 More than one prior cytotoxic chemotherapy or biologic therapy for treatment of CRPC Prior chemotherapy with mitoxantrone or other anthracyclines (ie, doxorubicin, daunomycin, epirubicin and idarubicin) Current enrollment in an investigational drug or device study or participation in such a study within 30 days of Cycle 1 Day 1 Prior flutamide (Eulexin) treatment within 4 weeks of Cycle 1 Day 1 Prior bicalutamide (Casodex), nilutamide (Nilandron, Anandron) within 6 weeks of Cycle 1 Day 1 Previous abiraterone acetate or other investigational CYP17 inhibitor (eg, TAK-700) Previous investigational antiandrogens (eg, MDV3100, BMS-641988) Patients receiving anti-coagulant therapy Condition or situation which, in the investigator's opinion, may put the patient at significant risk, may confound the study results, or may interfere significantly with patient's participation in the study

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>Patients will take 1000 mg of abiraterone acetate once daily plus prednisone 5 mg twice daily orally (by mouth) until disease progression. | Drug: Abiraterone acetate<br>* Abiraterone acetate 1000 mg (4 x 250 mg tablets) administered orally once daily.<br>Drug: Prednisone<br>* Prednisone 5 mg tablets administered orally twice daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean maximal change in electrocardiogram QTc |  | Baseline on Day -1 of Cycle 1 compared with Day 1 of Cycle 1, Cycle 2, Cycle 4 and every third cycle thereafter | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with change from baseline electrocardiogram QTc >30 msec |  | Pre-dose Cycles 1, 2, 4, and every third cycle after Cycle 4, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose, and end of study visit (4 weeks after last dose of study drug) | 
| Number of participants with change from baseline electrocardiogram QTc >60 msec |  | Pre-dose Cycles 1, 2, 4, and every third cycle after Cycle 4, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose, and end of study visit (4 weeks after last dose of study drug) | 
| Number of participants affected by an adverse event |  | Up to 30 days after the last dose of study medication | 
| Number of participants with change in cortrosyn stimulation test |  | Baseline and end of study visit (4 weeks after last dose of study drug) | 
| Number of participants with change in serum blood levels of testosterone |  | Baseline and end of study visit (4 weeks after last dose of study drug) | 
| Number of participants with change in adrenocorticotropic hormone |  | Baseline and end of study visit (4 weeks after last dose of study drug) | 
| Mean plasma concentrations of abiraterone |  | Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Maximum plasma concentrations of abiraterone |  | Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Time to reach the maximum plasma concentration of abiraterone |  | Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Area under the plasma-concentration-time curve from time 0 to the last quantifiable concentration of abiraterone |  | Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Area under the plasma-concentration-time curve from time 0 to infinite time of abiraterone |  | Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Elimination half-life of abiraterone |  | Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose | 
| Radiographic progression free survival |  | Up to Month 60 | 
| Overall survival |  | Up to Month 60 | 
| Number of participants with prostate specific antigen response |  | Week 12 | 
| Time to prostate specific antigen progression according to Prostate Cancer Working Group 2 criteria |  | Up to Month 60 | 
| Number of participants with objective radiographic response according to Prostate Cancer Working Group 2 criteria |  | Up to Month 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate neoplasms, Metastatic castration resistant prostate cancer, Abiraterone acetate, CB7630