A QT/QTc and Multi-dose PK Study of Abiraterone Acetate (CB7630) Plus Prednisone in Patients With Metastatic Castration- Resistant Prostate Cancer
Overview
- Phase
- Phase 1
- Intervention
- Abiraterone acetate
- Conditions
- Prostate Neoplasms
- Sponsor
- Janssen Research & Development, LLC
- Enrollment
- 33
- Locations
- 4
- Primary Endpoint
- Mean maximal change in electrocardiogram QTc
- Status
- Completed
- Last Updated
- 13 years ago
Overview
Brief Summary
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
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
Abiraterone acetate
Patients will take 1000 mg of abiraterone acetate once daily plus prednisone 5 mg twice daily orally (by mouth) until disease progression.
Intervention: Abiraterone acetate
Abiraterone acetate
Patients will take 1000 mg of abiraterone acetate once daily plus prednisone 5 mg twice daily orally (by mouth) until disease progression.
Intervention: Prednisone
Outcomes
Primary Outcomes
Mean maximal change in electrocardiogram QTc
Time Frame: Baseline on Day -1 of Cycle 1 compared with Day 1 of Cycle 1, Cycle 2, Cycle 4 and every third cycle thereafter
Secondary Outcomes
- 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)