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 - Full Text View

Sponsors and Collaborators:	Sidney Kimmel Comprehensive Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00334542

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 Procedure: laboratory biomarker analysis Procedure: mammography Procedure: pharmacological study	Phase II

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer Mammography

Drug Information available for: Simvastatin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Open Label
Official Title:	A Phase II Study of Simvastatin in Women at High Risk for a New Breast Cancer

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Change in a panel of biomarkers (high-sensitivity C-reactive protein [hsCRP], lipid profile, circulating estrogens, and contralateral breast density) from baseline [ Designated as safety issue: No ]

Secondary Outcome Measures:

Prevalence of breast gene (estrogen receptor [ER]-α and ER-β, cyclin D2, RAR-β, Twist, RASSF1A, and HIN-1) hypermethylation [ Designated as safety issue: No ]
Prevalence of Akt and p-Akt activation by contralateral core breast biopsies [ Designated as safety issue: No ]

Estimated Enrollment:	50
Study Start Date:	March 2006
Estimated Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Detailed Description:

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

Criteria

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00334542

Locations

United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Recruiting
Baltimore, Maryland, United States, 21231-2410
Contact: Clinical Trials Office - Sidney Kimmel Comprehensive Cancer Ce 410-955-8804 jhcccro@jhmi.edu
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Recruiting
Boston, Massachusetts, United States, 02115-6084
Contact: Judy Garber, MD 617-632-2282 judy_garber@dfci.harvard.edu

Sponsors and Collaborators

Sidney Kimmel Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Vered Stearns, MD

Sidney Kimmel Comprehensive Cancer Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000477214, JHOC-J0485, JHOC-SKCCC-J0485, JHOC-04100404
Study First Received:	June 7, 2006
Last Updated:	November 21, 2008
ClinicalTrials.gov Identifier:	NCT00334542
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Carcinoma, Ductal
Skin Diseases
Simvastatin
Carcinoma in Situ
Breast Neoplasms
Carcinoma, Ductal, Breast

Carcinoma, Intraductal, Noninfiltrating
Adenocarcinoma
Breast Diseases
Neoplasms, Glandular and Epithelial
Carcinoma

Additional relevant MeSH terms:

Antimetabolites
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses

Antilipemic Agents
Enzyme Inhibitors
Anticholesteremic Agents
Neoplasms, Ductal, Lobular, and Medullary
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009