Open Label Pharmacodynamic Study of Abiraterone Acetate in the Treatment of Metastatic, Castration Resistant Prostate Cancer
I. To determine the magnitude of tissue testosterone suppression by abiraterone acetate in
metastatic castrate-resistant prostate cancer (CRPC) (resistant to luteinizing
hormone-releasing hormone [LHRH] agonist or orchiectomy ± antiandrogen) after one month of
treatment to establish tissue based mechanism of action.
I. To determine the ability of abiraterone acetate to suppress tumor testosterone after 12
weeks of treatment.
II. To determine tissue testosterone from metastasis at time of progression during
abiraterone acetate treatment.
III. To determine response to dose escalation of abiraterone acetate and associate response
to tumor androgen levels prior to dose escalation.
IV. To determine potential mechanisms of resistance to abiraterone acetate by analyzing
tissue androgen levels at baseline and at progression, evaluating wild type and splice
variant androgen receptor (AR) levels at baseline and at time of progression and
complementary deoxyribonucleic acid (cDNA) microarray at progression.
V. To determine if micro-ribonucleic acid (RNA) acquired from peripheral blood reflect
molecular changes in tumor metastases and are a potential biomarker for mechanisms of
sensitivity and resistance.
Patients receive abiraterone acetate orally (PO) once daily (QD) on days 1-28 and prednisone
PO twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease
progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Change in tissue testosterone, dihydrotestosterone (DHT), androstenedione and dehydroepiandrosterone (DHEA)
A 2-sided paired t-test will be used and an attained significance level of 5% will be considered statistically significant.
From baseline to week 4
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
United States: Food and Drug Administration
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium||Seattle, Washington 98109|