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

Prostate Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00910754
• Other study ID #: CR016942
• Secondary ID: COU-AA-006
• Status: Completed
• Phase: Phase 1
• First received: May 28, 2009
• Last updated: April 11, 2013
• Start date: May 2009
• Est. completion date: May 2012

Study information

• Verified date: April 2013
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: May 2012
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostate Neoplasms
• Prostatic Neoplasms

Intervention

Drug:
• Abiraterone acetate
Abiraterone acetate 1000 mg (4 x 250 mg tablets) administered orally once daily.
• Prednisone
Prednisone 5 mg tablets administered orally twice daily.

Locations

Country	Name	City	State
Canada	BC Cancer Agency-Vancouver	Vancouver	British Columbia
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	South Texas Accelerated Research Therapeutics	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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)	No
Secondary	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)	No
Secondary	Number of participants affected by an adverse event		Up to 30 days after the last dose of study medication	Yes
Secondary	Number of participants with change in cortrosyn stimulation test		Baseline and end of study visit (4 weeks after last dose of study drug)	No
Secondary	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)	No
Secondary	Number of participants with change in adrenocorticotropic hormone		Baseline and end of study visit (4 weeks after last dose of study drug)	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Radiographic progression free survival		Up to Month 60	No
Secondary	Overall survival		Up to Month 60	No
Secondary	Number of participants with prostate specific antigen response		Week 12	No
Secondary	Time to prostate specific antigen progression according to Prostate Cancer Working Group 2 criteria		Up to Month 60	No
Secondary	Number of participants with objective radiographic response according to Prostate Cancer Working Group 2 criteria		Up to Month 60	No

External Links

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