Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

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.

Further Study Information

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 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

Trial Contact Information

Trial Lead Organizations/Sponsors

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Vered Stearns

Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00334542
Information obtained from ClinicalTrials.gov on December 14, 2011

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