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Phase II Study of Simvastatin in Primary Breast Cancer; Test of Its Potential Selectivity on Basal Subtype Breast Cancer

Phase 2
18 Years
Open (Enrolling)
Breast Cancer

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Trial Information

Phase II Study of Simvastatin in Primary Breast Cancer; Test of Its Potential Selectivity on Basal Subtype Breast Cancer

Primary Objectives

1. Evaluate the biological response (proliferation and apoptosis) of Simvastatin in primary
breast cancer.

2. Evaluate the cell type specificity of Simvastatin effect on basal subtype breast cancer,
especially cells with CD44+/CD24- immunophenotype in the primary tumor. Secondary objectives

1. To study cellular response to Simvastatin in transriptome.

2. To obtain gene expression signature that predict Simvastatin biological effects.

3. To identify genetic polymorphisms that may influence Simvastatin pharmacokinetics
and/or biological effects on breast cancer.

4. To correlate tumor and plasma proteomics with tumor gene expression changes, and to
identify tumor and/or serum protein markers that predict Simvastatin biological

5. To correlate peripheral blood mononuclear cell gene expression changes with tumor gene
expression changes, and to identify blood gene markers that may predict Simvastatin
biological effects. VI. Abstract of Research Proposal In no more than 300 words,
describe concisely the specific aims, hypotheses, methodology and approach of the
application, indicating where appropriate the application's importance to science or
medicine. The abstract must be self-contained so that it can serve as a succinct and
accurate description of the application when separated from it. Please use lay terms.
If this not possible, the technical and medical terms should be explained in simple
language. We hypothesize that Simvastatin administration would result in selective
killing of the basal subtype of breast cancer, in particular, CD44+/CD24- breast cancer
cells in primary tumor. We further hypothesize that tumor genomic changes would
correlate with tumor response to Simvastatin. We are also looking to correlate
Simvastatin biological effects with the expression pattern of initial status of primary
tumor. In addition, we hypothesize that Simvastatin-induced tumor gene expression
changes may correlate with tumor and plasma proteomics, peripheral blood mononuclear
cell gene expression changes, and pharmacogenetics, and that these analyses may further
refine the selection of patients most likely to benefit from Simvastatin. This is a
single-centre, open-label, phase II study of Simvastatin in resectable primary breast

A total of 100 patients with measurable, resectable, primary breast tumor will be enrolled
to receive 10-21 days of Simvastatin at a dose of 20 mg daily before definitive breast
cancer surgery. Pre-treatment tumor biopsy will be obtained from each subject before
starting Simvastatin. Subjects will take Simvastatin at a dose of 20 mg daily for 10-21
days, prior to definitive breast cancer surgery. The post-treatment tumor biopsy will be
obtained at surgery. At each tumor biopsy, 3-4 tumor samples will be obtained through the
same needle track. One tumor core at each time point will be fixed in formalin for
histological examination and immunohistochemical studies. The remaining tumor cores will be
stored in liquid nitrogen for subsequent RNA and protein extraction for gene expression and
proteomics studies. Blood samples will be obtained before and after 10-21 days of
Simvastatin treatment for Simvastatin pharmacokinetic analysis, plasma proteomics and
peripheral mononuclear cell gene expression analysis. 10 ml blood will be taken from each
participant for genotyping studies.

Inclusion Criteria:

- Female, age >= 18 years. Page 14 of 28

- Histologic or cytologic diagnosis of breast carcinoma.

- Clinical T1-3 breast cancer with measurable primary breast tumor which is amenable to
free-hand core biopsy

- Patients scheduled for definitive surgery

- Patients must not have received prior or scheduled to receive chemotherapy, hormonal
therapy, radiotherapy, targeted therapy, or immunotherapy for the treatment of breast

- Karnofsky performance status of 70 or higher.

- Normal creatinine kinase

- Adequate organ function including the following:

- Bone marrow:

- Absolute neutrophil (segmented and bands) count (ANC) >= 1.5 x 109/L Platelets >= 100
x 109/L

- Hepatic:

- Bilirubin within normal range

- ALT or AST <1.5 x upper limit normal

- Renal:

- creatinine <= 1.5 x upper limit normal

- Signed informed consent from patient or legal representative.

- Patients with reproductive potential must use an approved contraceptive method if
appropriate (eg, intrauterine device, birth control pills, or barrier device) during
and for three months after the study. Females with childbearing potential must have a
negative pregnancy test within 7 days prior to study enrollment.

Exclusion Criteria:

- Current treatment with HMG-CoA reductase inhibitors or other lipid lowering drugs

- Treatment within the last 30 days with any investigational drug.

- Concurrent administration of any other tumor therapy, including cytotoxic
chemotherapy, hormonal therapy, and immunotherapy.

- Known hypersensitivity to Simvastatin

- Active liver disease or unexplained persistent elevations of serum transminases

- Pregnancy.

- Breast feeding

- Serious concomitant disorders that would compromise the safety of the patient or
compromise the patient's ability to complete the study, at the discretion of the

- Second primary malignancy that is clinically detectable at the time of consideration
for study enrollment.

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Soo Chin Lee, MBBS, MRCP

Investigator Role:

Principal Investigator

Investigator Affiliation:

National University Hospital, Singapore


Singapore: Domain Specific Review Boards

Study ID:




Start Date:

March 2008

Completion Date:

Related Keywords:

  • Breast Cancer
  • Breast Neoplasms