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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT00910754
First received: May 28, 2009
Last updated: April 11, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Prostate Neoplasms
Drug: Abiraterone acetate
Drug: Prednisone
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A QT/QTc and Multi-dose PK Study of Abiraterone Acetate (CB7630) Plus Prednisone in Patients With Metastatic Castration- Resistant Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of participants with change from baseline electrocardiogram QTc >30 msec [ Time Frame: 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) ] [ Designated as safety issue: No ]
  • Number of participants with change from baseline electrocardiogram QTc >60 msec [ Time Frame: 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) ] [ Designated as safety issue: No ]
  • Number of participants affected by an adverse event [ Time Frame: Up to 30 days after the last dose of study medication ] [ Designated as safety issue: Yes ]
  • Number of participants with change in cortrosyn stimulation test [ Time Frame: Baseline and end of study visit (4 weeks after last dose of study drug) ] [ Designated as safety issue: No ]
  • Number of participants with change in serum blood levels of testosterone [ Time Frame: Baseline and end of study visit (4 weeks after last dose of study drug) ] [ Designated as safety issue: No ]
  • Number of participants with change in adrenocorticotropic hormone [ Time Frame: Baseline and end of study visit (4 weeks after last dose of study drug) ] [ Designated as safety issue: No ]
  • Mean plasma concentrations of abiraterone [ Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose ] [ Designated as safety issue: No ]
  • Maximum plasma concentrations of abiraterone [ Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose ] [ Designated as safety issue: No ]
  • Time to reach the maximum plasma concentration of abiraterone [ Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose ] [ Designated as safety issue: No ]
  • Area under the plasma-concentration-time curve from time 0 to the last quantifiable concentration of abiraterone [ Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose ] [ Designated as safety issue: No ]
  • Area under the plasma-concentration-time curve from time 0 to infinite time of abiraterone [ Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose ] [ Designated as safety issue: No ]
  • Elimination half-life of abiraterone [ Time Frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose ] [ Designated as safety issue: No ]
  • Radiographic progression free survival [ Time Frame: Up to Month 60 ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to Month 60 ] [ Designated as safety issue: No ]
  • Number of participants with prostate specific antigen response [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Time to prostate specific antigen progression according to Prostate Cancer Working Group 2 criteria [ Time Frame: Up to Month 60 ] [ Designated as safety issue: No ]
  • Number of participants with objective radiographic response according to Prostate Cancer Working Group 2 criteria [ Time Frame: Up to Month 60 ] [ Designated as safety issue: No ]

Enrollment: 33
Study Start Date: May 2009
Study Completion Date: May 2012
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00910754

Locations
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Buffalo, New York, United States
United States, South Carolina
Carolina Urologic Research Center
Myrtle Beach, South Carolina, United States, 29572
Myrtle Beach, South Carolina, United States
United States, Texas
South Texas Accelerated Research Therapeutics
San Antonio, Texas, United States, 78229
San Antonio, Texas, United States
Canada, British Columbia
BC Cancer Agency-Vancouver
Vancouver, British Columbia, Canada, V5Z 4E6
Vancouver, British Columbia, Canada
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

Additional Information:
No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT00910754     History of Changes
Other Study ID Numbers: CR016942, COU-AA-006
Study First Received: May 28, 2009
Last Updated: April 11, 2013
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Janssen Research & Development, LLC:
Prostate neoplasms
Metastatic castration resistant prostate cancer
Abiraterone acetate
CB7630

Additional relevant MeSH terms:
Neoplasms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Prednisone
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 16, 2014