Abiraterone Acetate in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer
This phase II trial studies how well giving abiraterone acetate works in treating patients with metastatic hormone-resistant prostate cancer. Abiraterone acetate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Adenocarcinoma of the Prostate
Hormone-resistant Prostate Cancer
Recurrent Prostate Cancer
Stage IV Prostate Cancer
Drug: abiraterone acetate
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Open Label Pharmacodynamic Study of Abiraterone Acetate in the Treatment of Metastatic, Castration Resistant Prostate Cancer.|
- Change in tissue testosterone, dihydrotestosterone (DHT), androstenedione and dehydroepiandrosterone (DHEA) [ Time Frame: From baseline to week 4 ] [ Designated as safety issue: No ]A 2-sided paired t-test will be used and an attained significance level of 5% will be considered statistically significant.
- Ability of abiraterone acetate to suppress tumor testosterone, assessed by changes in testosterone levels [ Time Frame: From baseline to 12 weeks ] [ Designated as safety issue: No ]
- Tissue testosterone from metastasis at time of progression [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
- PSA response to dose escalation of abiraterone acetate, defined as decline from the PSA at initiation of therapy and with dose escalation of abiraterone acetate, assessed using Prostate Cancer Working Group 2 (PCWG2) criteria [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]The subsequent response to dose escalation (if any) will be correlated with tumor androgens.
- Potential mechanisms of resistance to abiraterone acetate, determined by assessment of changes in tissue androgen levels, evaluating wild type and splice variant AR levels, and cDNA microarray [ Time Frame: Baseline and time of progression, up to 4 years ] [ Designated as safety issue: No ]
- Reflection of molecular changes in tumor metastases by microRNA (miRNA) acquired from peripheral blood [ Time Frame: From baseline to time of progression, up to 4 years ] [ Designated as safety issue: No ]Candidate miRNA strongly associated with response or progression will be quantitated in biopsy tissue as possible.
|Study Start Date:||December 2012|
|Estimated Primary Completion Date:||January 2017 (Final data collection date for primary outcome measure)|
Experimental: Treatment (abiraterone acetate and prednisone)
Patients receive abiraterone acetate PO QD on days 1-28 and prednisone PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: abiraterone acetate
Other Names:Drug: prednisone
Other Names:Other: laboratory biomarker analysis
Correlative studiesOther: pharmacological study
Other Name: pharmacological studies
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 at clinical progression.
IV. To determine potential mechanisms of resistance to abiraterone acetate by analyzing pharmacokinetics at clinical progression, tissue androgen levels at baseline and at radiographic 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.
VI. To evaluate pharmacokinetics of dose escalated abiraterone at 1000 mg twice daily.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01503229
|United States, Washington|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium||Recruiting|
|Seattle, Washington, United States, 98109|
|Contact: Robert B. Montgomery 206-598-0860|
|Principal Investigator: Robert B. Montgomery|
|Principal Investigator:||Robert Montgomery||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|