Abiraterone Acetate in Treating Postmenopausal Women With Advanced or Metastatic Breast Cancer
RATIONALE: Abiraterone acetate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I/II trial is studying the side effects and best dose of abiraterone acetate and to see how well it works in treating postmenopausal women with advanced or metastatic breast cancer.
Drug: abiraterone acetate
Other: laboratory biomarker analysis
Other: pharmacogenomic studies
|Study Design:||Allocation: Non-Randomized
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Cancer Research UK Phase I/II Open Label Study to Evaluate the Safety, Endocrine Effects and Anti-tumour Activity of Abiraterone Acetate (CB7630) in Patients With Oestrogen (ER) or Androgen Receptor (AR) Positive Advanced or Metastatic Breast Carcinoma|
- Causality of each adverse event and grading severity as measured by NCI CTCAE v3.0 (Phase I)
- Maximum tolerated dose (MTD) of abiraterone acetate (Phase I)
- Proportion of patients with stable disease for ≥ 24 weeks or objective response as measured by RECIST criteria (Phase II)
- Plasma levels of abiraterone acetate as measured by liquid chromatography/tandem mass spectrometry assay (Phase I)
- Relationship between dose and endocrine response (Phase I)
- Duration of objective tumor response as measured by RECIST criteria (Phase II)
- Relationship between tumor response and endocrine response (Phase II)
- Median overall survival (Phase II)
|Study Start Date:||October 2008|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
- To evaluate the safety and tolerability of abiraterone acetate in postmenopausal women with estrogen receptor- or androgen receptor-positive advanced or metastatic breast cancer. (Phase I)
- To determine the recommended phase II dose of this drug in these patients. (Phase I)
- To evaluate the clinical benefit rate of this drug at 24 weeks in these patients. (Phase II)
- To study the pharmacokinetics of this drug in these patients. (Phase I)
- To determine the endocrine impact of this drug on the pituitary-adrenal-gonad endocrine axis. (Phase I)
- To estimate the duration of objective tumor response in these patients. (Phase II)
- To correlate response rates and duration of response with the endocrine profile in these patients. (Phase II)
- To determine overall survival of these patients. (Phase II)
- To enumerate and molecularly characterize circulating tumor cells.
- To identify normal genetic variations that predict resistance to this drug using pharmacogenomic analysis.
OUTLINE: This is a multicenter, phase I study followed by a phase II study. Patients enrolled in the phase II portion of the study are stratified according to hormone receptor status (estrogen receptor [ER]-positive and any androgen receptor [AR] status vs AR-positive and ER-negative).
Patients receive oral abiraterone acetate once daily on days 1-28. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
Blood samples are collected periodically and analyzed for pharmacokinetic assays (phase I only), pharmacodynamic assays, circulating tumor cells, and pharmacogenomic analysis.
After completion of study treatment, patients are followed for 28 days.
Peer Reviewed and Funded or Endorsed by Cancer Research UK.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00755885
|Velindre Cancer Centre|
|Whitchurch, Cardiff, United Kingdom, CF14 2TL|
|London, England, United Kingdom, SE1 9RT|
|Royal Marsden - Surrey|
|Sutton, England, United Kingdom, SM2 5PT|
|University of Birmingham,|
|Birmingham, United Kingdom, B15 2TT|
|Western General Hospital|
|Edinburgh, United Kingdom, EH4 2XU|
|The Beatson West of Scotland Cancer Centre|
|Glasgow, United Kingdom, G12 0YN|
|Principal Investigator:||Johann Sebastian de Bono, MD||Cancer Research UK|