A Phase II Study of Increased-Dose Abiraterone Acetate in Patients With Castration Resistant Prostate Cancer
The purpose of this study is to find out what effects, good and/or bad,an increased dose of Abiraterone Acetate in combination with prednisone has on patients and their prostate cancer. This study will investigate whether an increased-dose (2,000mg daily) is safe and potentially effective when given to patients whose cancer has grown while taking the standard dose.
Castration Resistant Prostate Cancer
Drug: Abiraterone Acetate
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Increased-Dose Abiraterone Acetate in Patients With Castration Resistant Prostate Cancer (CRPC)|
- PSA response proportion to increased-dose Abiraterone Acetate for patients who experienced disease progression following standard dose Abiraterone Acetate therapy [ Time Frame: Estimated up to 24 months ] [ Designated as safety issue: No ]Evaualtion at 12 weeks post increased dose therapy initiation and then every 4 weeks until PD#2.
- Safety of treatment [ Time Frame: Estimated up to 24 months ] [ Designated as safety issue: Yes ]Toxicities will be graded for management according to NCI-CTCAE version 4.0.
- Clinical benefit (time to PSA progression and progression free survival) for patients treated with increased dose Abiraterone Acetate [ Time Frame: Estimated up to 24 months ] [ Designated as safety issue: No ]
- Serum concentration of Abiraterone Acetate [ Time Frame: Estimated up to 24 months ] [ Designated as safety issue: Yes ]Pharmacokinetic assessment at the initiation of standard dose therapy, at the time of initial disease progression, at the time of a response to increased-dose Abiraterone Acetate, and at the time of disease progression on increased-dose therapy.
- Circulating androgen levels [ Time Frame: Estimated up to 24 months ] [ Designated as safety issue: No ]Testosterone, DHEA, DHEA-S and androstenedione will be measured prior to the start of initial Abiraterone Acetate 1000mg mg daily and then every 2 cycles during study therapy.
|Study Start Date:||March 2013|
|Estimated Study Completion Date:||December 2017|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
|Experimental: Abiraterone Acetate in combination with prednisone||
Drug: Abiraterone Acetate
Standard dose: 1,000 mg, once daily, oral administration
Increased dose: 1,000 mg, twice daily, oral administration
Other Name: ZytigaDrug: Prednisone
5 mg, twice daily, oral administration
This is a phase II multicenter trial of Abiraterone Acetate in patients with progressive prostate cancer despite androgen deprivation with a particular focus on the pharmacokinetic, pharmacodynamic, and pharmacogenomic events occurring at the time of apparent drug resistance. All eligible patients will have baseline (prior to taking the first dose of Abiraterone Acetate 1000mg/daily) measures of routine clinical variables along with measurements of baseline and treatment related changes in testosterone, androgen, and endocrine levels, genotyping of SNPs in the selected enzymes known to be directly inhibited by Abiraterone Acetate, and collection of circulating tumor cells. All patients will be requested to consent for biopsies which will be performed prior to treatment and at the time of disease progression on standard dose Abiraterone Acetate therapy. These biopsies will be analyzed for expression of an AR-signature as well as for microarray analysis to explore changes in methylation, and expression of CYP17A1 and other androgen synthesis genes.
Subjects will then begin daily oral therapy with Abiraterone Acetate 1000mg po daily with physiologic prednisone 5mg BID replacement. No food should be consumed for at least 2 hours before the dose of Abiraterone Acetate and for at least 1 hour after the dose of Abiraterone Acetate is taken. PSA will be followed monthly. Abiraterone Acetate will be supplied by Janssen Services. At the end of the first month, the third month, and then every three months thereafter, Abiraterone Acetate, testosterone, and androgen levels will be followed. Subjects not achieving a greater than or equal to 30% PSA decline at 12 weeks will be taken off study. At the time of progression (defined by RECIST criteria OR by the Prostate Cancer Working Group 2 (PCWG) criteria as a 25% increase in PSA above the nadir and an increase in the absolute value PSA of at least 2ng/dl or back to baseline confirmed at least 2 weeks afterward) for subjects who achieved an initial greater than or equal to 30% PSA decline (referred to as Progressive Disease (PD) #1), subjects will begin taking Abiraterone Acetate 1000 mg po BID. Patients will continue to take prednisone 5mg BID and will continue this therapy until a second progression at which point they will be withdrawn from the study. While 1000 mg po BID is not the FDA recommended dose, it is the dose to be investigated in this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01637402
|United States, California|
|UCSF Helen Diller Family Comprehensive Cancer Center|
|San Francisco, California, United States, 94115|
|United States, Oregon|
|Oregon Health and Science University|
|Portland, Oregon, United States, 79239|
|Study Chair:||Terence Friedlander, MD||University of California, San Francisco|