Abiraterone Acetate in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01503229|
Recruitment Status : Completed
First Posted : January 2, 2012
Last Update Posted : January 19, 2018
|Condition or disease||Intervention/treatment||Phase|
|Hormone-Resistant Prostate Cancer Metastatic Prostate Carcinoma Recurrent Prostate Carcinoma Stage IV Prostate Adenocarcinoma||Drug: Abiraterone Acetate Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Prednisone||Phase 2|
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 (abiraterone acetate) at 1000 mg twice daily.
Patients receive abiraterone acetate orally (PO) once daily (QD) 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||28 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Open Label Pharmacodynamic Study of Abiraterone Acetate in the Treatment of Metastatic, Castration Resistant Prostate Cancer|
|Actual Study Start Date :||December 2012|
|Actual Primary Completion Date :||September 12, 2017|
|Actual Study Completion Date :||September 12, 2017|
Experimental: Treatment (abiraterone acetate and prednisone)
Patients receive abiraterone acetate PO QD 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: Laboratory Biomarker Analysis
Other: Pharmacological Study
- Change in tissue testosterone, dihydrotestosterone (DHT), androstenedione and dehydroepiandrosterone (DHEA) [ Time Frame: From baseline to week 4 ]Tissue testosterone, DHT, androstenedione, and DHEA measurements will be summarized numerically and graphically using plots of patient- and cohort-specific longitudinal patterns and side-by-side boxplots at each time point. 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 ]
- 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 ]
- 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 criteria [ Time Frame: Up to 4 years ]The subsequent response to dose escalation (if any) will be correlated with tumor androgens.
- 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 ]Candidate miRNA strongly associated with response or progression will be quantitated in biopsy tissue as possible.
- Tissue testosterone from metastasis at time of progression [ Time Frame: Up to 4 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01503229
|United States, Washington|
|Fred Hutch/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Robert Montgomery||Fred Hutch/University of Washington Cancer Consortium|