Simvastatin in Preventing a New Breast Cancer in Women at High Risk for a New Breast Cancer
RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of simvastatin may keep cancer from coming back in women who are at high risk for a new breast cancer after undergoing surgery for ductal carcinoma in situ or stage I, stage II, or stage III breast cancer.
PURPOSE: This phase II trial is studying how well simvastatin works in preventing a new breast cancer in women at high risk for a new breast cancer after undergoing surgery for ductal carcinoma in situ or stage I, stage II, or stage III breast cancer.
|Study Design:||Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||A Phase II Study of Simvastatin in Women at High Risk for a New Breast Cancer|
- Change in a Panel of Biomarkers (High-sensitivity C-reactive Protein [hsCRP], Lipid Profile, and Circulating Estrogens) From Baseline [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]
- Change in a Panel of Biomarkers (Contralateral Breast Density) From Baseline [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]
- Prevalence of Breast Gene (Estrogen Receptor [ER]-α and ER-β, Cyclin D2, RAR-β, Twist, RASSF1A, and HIN-1) Hypermethylation [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]
- Prevalence of Akt and p-Akt Activation by Contralateral Core Breast Biopsies [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]
|Study Start Date:||March 2006|
|Study Completion Date:||November 2011|
|Primary Completion Date:||June 2009 (Final data collection date for primary outcome measure)|
Simvastatin 40 mg for 24-28 weeks
24-28 weeks of simvastatin
Other Name: Zocor
- Describe changes from baseline in a panel of biomarkers (high-sensitivity C-reactive protein [hsCRP], lipid profile, circulating estrogens, and contralateral breast density) in women at high risk of developing new breast cancer who have undergone surgical resection for history of ductal carcinoma in situ or stage I-III invasive breast cancer treated with simvastatin.
- Correlate changes in the panel of biomarkers with wild-type versus polymorphic 3-hydroxyl-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase in women treated with simvastatin.
- Evaluate methylation status across a panel of genes that are known to be frequently and specifically hypermethylated in ductal carcinoma in situ (DCIS) and invasive breast cancer (estrogen receptor [ER]-α and ER-β, cyclin D2, RAR-β, Twist, RASSF1A, and HIN-1) and correlate change in cumulative methylation with change in hsCRP, lipid profile, contralateral breast density, estrogen concentrations, and pharmacogenetics.
- Measure changes in the phosphoinositide 3'-kinase (PI3K)/protein kinase B (Akt) signaling pathway (Akt and p-Akt) before and after treatment with simvastatin.
OUTLINE: This is a multicenter study. Patients are stratified according to menopausal status (pre- vs post-menopausal).
Patients receive oral simvastatin once daily for 24-28 weeks in the absence of disease progression or unacceptable toxicity.
Patients undergo blood collection at baseline and at the end of study treatment for pharmacogenetic and biomarker correlative studies. Patients undergo mammography and measurement of breast density of the contralateral breast at baseline and at the end of study treatment.
Quality of life is assessed at baseline and at the end of study treatment.
PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00334542
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21231-2410|
|United States, Massachusetts|
|Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115-6084|
|Principal Investigator:||Vered Stearns, MD||Sidney Kimmel Comprehensive Cancer Center|