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

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

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.

Study Overview

• Status: Completed
• Conditions: Prostate Neoplasms
• Intervention / Treatment: Drug: Abiraterone acetate; Drug: Prednisone

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.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BC Cancer Agency-Vancouver
• United States
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Buffalo, New York, United States
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Carolina Urologic Research Center
    • Myrtle Beach, South Carolina, United States
  • Texas
    • San Antonio, Texas, United States
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Abiraterone acetate; 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; Abiraterone acetate 1000 mg (4 x 250 mg tablets) administered orally once daily.; Drug: Prednisone; Prednisone 5 mg tablets administered orally twice daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	Time Frame
Number of participants affected by an adverse event	Up to 30 days after the last dose of study medication
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 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

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: May 28, 2009
• First Submitted That Met QC Criteria: May 29, 2009
• First Posted (Estimate): June 1, 2009

Study Record Updates

• Last Update Posted (Estimate): April 12, 2013
• Last Update Submitted That Met QC Criteria: April 11, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: Abiraterone acetate; Prostate neoplasms; Metastatic castration resistant prostate cancer; CB7630
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Steroid Synthesis Inhibitors; Prednisone; Abiraterone Acetate
• Other Study ID Numbers: CR016942; COU-AA-006 (Other Identifier: Janssen Research & Development, LLC)