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A Phase II Study of Simvastatin in Women at High Risk for a New Breast Cancer

Phase 2
18 Years
Not Enrolling
Breast Cancer

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Trial Information

A Phase II Study of Simvastatin in Women at High Risk for a New Breast Cancer



- 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


- 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.

Inclusion Criteria


- History of histologically confirmed breast cancer, meeting 1 of the following staging

- 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


- 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)


- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Outcome Measure:

Change in a Panel of Biomarkers (High-sensitivity C-reactive Protein [hsCRP], Lipid Profile, and Circulating Estrogens) From Baseline

Outcome Time Frame:

Baseline and week 24

Safety Issue:


Principal Investigator

Vered Stearns, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Sidney Kimmel Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:

JHOC-J0485, CDR0000477214



Start Date:

March 2006

Completion Date:

November 2011

Related Keywords:

  • Breast Cancer
  • 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
  • Breast Neoplasms



Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland  21231-2410
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute Boston, Massachusetts  02115