Clinical Trials /

The Effect of Simvastatin on Breast Cancer Cell Growth in Women With Stage I-II Breast Cancer

NCT03454529

Description:

The purpose of this pilot phase II trial is to identify the molecular and genetic mechanisms by which statins influence breast cancer cell proliferation. Simvastatin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and reduce the aggressiveness of breast cancer cells.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: The Effect of Simvastatin on Breast Cancer Cell Growth in Women With Stage I-II Breast Cancer
  • Official Title: The Effect of Statins on Markers of Breast Cancer Proliferation and Apoptosis in Women With Early Stage Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 2017-073
  • SECONDARY ID: NCI-2018-00044
  • SECONDARY ID: 2017-073
  • SECONDARY ID: P30CA022453
  • NCT ID: NCT03454529

Conditions

  • Invasive Breast Carcinoma
  • Stage I Breast Cancer AJCC v7
  • Stage IA Breast Cancer AJCC v7
  • Stage IB Breast Cancer AJCC v7
  • Stage II Breast Cancer AJCC v6 and v7
  • Stage IIA Breast Cancer AJCC v6 and v7
  • Stage IIB Breast Cancer AJCC v6 and v7

Interventions

DrugSynonymsArms
SimvastatinMK 733, Synvinolin, ZocorTreatment (simvastatin)

Purpose

The purpose of this pilot phase II trial is to identify the molecular and genetic mechanisms by which statins influence breast cancer cell proliferation. Simvastatin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and reduce the aggressiveness of breast cancer cells.

Detailed Description

      PRIMARY OBJECTIVES:

      I. Evaluate the relationship between short-term use of oral simvastatin on change in
      expression of Ki-67 as a candidate biomarker of breast tumor proliferation among women with
      clinical stage 1 or 2- primary invasive breast cancer.

      II. Evaluate the relationship between short-term use of oral simvastatin on changes in other
      candidate predictive markers of breast tumor proliferation (cyclin D1 and P27), changes in a
      marker of apoptosis (cleaved caspase-3 [CC3]), changes in a marker of inflammation
      (c-reactive protein [CRP]) and as novel additional biomarkers changes in the composition of
      the plasma membrane (lipid rafts) and changes in activation of signaling markers
      (phosphorylation [p]Akt, pMAPK, pEGFR, PHER2).

      III. To conduct exploratory analyses comparing the effect of statins on breast tumor
      proliferation and apoptosis in groups defined by tumor expression of hydroxymethylglutaryl
      co-enzyme A (CoA) reductase (HMG-CoA), estrogen receptor (ER)/progesterone receptor (PR)
      status, HER2neu, and tumor grade.

      OUTLINE:

      Patients receive simvastatin orally (PO) daily for 2-4 weeks in the absence of disease
      progression or unacceptable toxicity.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (simvastatin)ExperimentalPatients receive simvastatin PO daily for 2-4 weeks in the absence of disease progression or unacceptable toxicity.
  • Simvastatin

Eligibility Criteria

        Inclusion Criteria:

          -  Provision of informed consent prior to any study specific procedures

          -  Histologic confirmation of invasive breast cancer with any measures of ER, PR and
             HER2neu

          -  Clinical stage I or II breast cancer for which there will be at least a 2 week period
             of time between diagnosis and definitive surgery

          -  Performance status (Eastern Cooperative Oncology Group [ECOG] 0-1)

          -  Not currently pregnant during the study; participants will be informed that the use of
             contraceptive pills is contraindicated because it may interfere with the study drug
             and it may be harmful to the woman who has been diagnosed with breast cancer

        Exclusion Criteria:

          -  Plans for administration of neoadjuvant chemotherapy or hormonal therapy

          -  Insufficient tissue on diagnostic core breast biopsy for analysis

          -  Previous or concurrent malignancy (with the exception of non-melanomatous skin cancer)

          -  Severe gastrointestinal disorder

          -  Current use of statins or fibrates for any time during the 3 months prior to the study

          -  Proven hypersensitivity to statins

          -  White blood cell (WBC) < 3,500/mm^3

          -  Platelet (Plt) < 120,000/mm^3

          -  Hemoglobin (HgB) < 10 g/dL

          -  Aspartate aminotransferase (AST) > 45 U/L

          -  Alanine aminotransferase (ALT) > 45 U/L

          -  Creatinine > 1.5 mg/dL

          -  Bilirubin > 1.15 mg/dL

          -  Creatine kinase measurement (CPK) > or = 250 mg/dL

          -  Central nervous system (CNS) diseases and major psychiatric diseases or inability to
             comply to the protocol procedures

          -  Active infections

          -  Cardiac failure, class I-IV

          -  Current anticoagulant or antiplatelet aggregation therapy

          -  Mitral and/or tricuspid valvopathy or valvular prosthesis; angina; severe arterial
             hypertension; chronic and/or paroxysmal atrial fibrillation; previous myocardial
             infarction

          -  Current lactation
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in Ki-67 expression assessed in tumor tissue by immunohistochemistry
Time Frame:Baseline up to 4 weeks
Safety Issue:
Description:Will be described as average pre-post differences in percent positive cells with 95% Wilson confidence intervals and tested with a paired t-test.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Michael Simon

Last Updated

January 28, 2019