Simvastatin in Preventing a New Breast Cancer 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
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Breast Cancer |
Drug: simvastatin Other: laboratory biomarker analysis Other: pharmacological study Procedure: radiomammography |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | 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, circulating estrogens, and 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 ]
| Enrollment: | 50 |
| Study Start Date: | March 2006 |
| Estimated Study Completion Date: | January 2013 |
| Primary Completion Date: | June 2009 (Final data collection date for primary outcome measure) |
OBJECTIVES:
Primary
- 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.
Secondary
- 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.
Tertiary
- 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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
History of histologically confirmed breast cancer, meeting 1 of the following staging criteria:
- Ductal carcinoma in situ
- Stage I-III invasive breast cancer
At least 3 months since completion of all intended local and systemic therapy, including mastectomy or lumpectomy with or without radiotherapy, adjuvant chemotherapy, and/or endocrine therapy
- May have declined recommended treatment provided all treatment intended/agreed upon by the patient and treating physician was completed ≥ 3 months ago
At least 1 healthy intact breast
- No prior radiotherapy or mastectomy
- Prior biopsies allowed
- Any hormone-receptor status
PATIENT CHARACTERISTICS:
- Female
- Pre- or post-menopausal
- ECOG performance status 0-2
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective nonhormonal contraception
- No active liver disease
- AST and ALT ≤ 3 times upper limit of normal
- Creatinine clearance ≥ 30 mL/min
- No prior hypersensitivity to any 3-hydroxyl-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase inhibitor or any of its components
- No other concurrent infectious, inflammatory, or autoimmune diseases (at the discretion of principal investigator)
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
No daily alcohol use > 3 standard drinks per day
- Standard drink defined as 10 grams of alcohol, which is equivalent to 285 mL of beer, 530 mL of light beer, 100 mL of wine, or 30 mL of liquor
- No selective estrogen receptor modulator or aromatase inhibitor within the past 3 months
- No hormone replacement therapy (HRT) within the past 3 months
No prior estrogen and/or progesterone HRT ≥ 5 years in duration
- Vaginal estrogen preparations allowed
- No concurrent HRT
- No other cholesterol-lowering drug, including a statin, within the past 3 months
- No concurrent itraconazole, ketoconazole, nefazodone, cyclosporine, HIV protease inhibitors, clarithromycin, erythromycin, mibefradil, carbamazepine, bosentan, chaparral, amiodarone, or verapamil
- No concurrent daily grapefruit juice consumption > 8 ounces per day
- No other concurrent agents or therapies intended to treat or prevent in situ or invasive breast cancer
Contacts and Locations| 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 |
More Information
Additional Information:
No publications provided
| Responsible Party: | Sidney Kimmel Comprehensive Cancer Center |
| ClinicalTrials.gov Identifier: | NCT00334542 History of Changes |
| Other Study ID Numbers: | JHOC-J0485, CDR0000477214, P50CA088843, P30CA006973, JHOC-J0485, JHOC-SKCCC-J0485, JHOC-04100404 |
| Study First Received: | June 7, 2006 |
| Last Updated: | June 11, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
|
breast cancer ductal breast carcinoma in situ breast cancer in situ stage I breast cancer |
stage II breast cancer stage IIIA breast cancer stage IIIB breast cancer stage IIIC breast cancer |
Additional relevant MeSH terms:
|
Breast Neoplasms Carcinoma in Situ Carcinoma, Intraductal, Noninfiltrating Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Adenocarcinoma |
Neoplasms, Ductal, Lobular, and Medullary Simvastatin Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Lipid Regulating Agents Therapeutic Uses Hydroxymethylglutaryl-CoA Reductase Inhibitors Anticholesteremic Agents Enzyme Inhibitors |
ClinicalTrials.gov processed this record on March 06, 2013
