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

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ClinicalTrials.gov Identifier: NCT03454529
Recruitment Status : Recruiting
First Posted : March 6, 2018
Last Update Posted : March 6, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Michael Simon, Barbara Ann Karmanos Cancer Institute

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
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 Other: Laboratory Biomarker Analysis Drug: Simvastatin Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Effect of Statins on Markers of Breast Cancer Proliferation and Apoptosis in Women With Early Stage Breast Cancer
Estimated Study Start Date : March 9, 2018
Estimated Primary Completion Date : May 31, 2020
Estimated Study Completion Date : May 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Simvastatin

Arm Intervention/treatment
Experimental: Treatment (simvastatin)
Patients receive simvastatin PO daily for 2-4 weeks in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Simvastatin
Given PO
Other Names:
  • MK 733
  • Synvinolin
  • Zocor




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


Other Outcome Measures:
  1. Changes in other candidate markers associated with breast tumor proliferation including cyclin D1 and P27 [ Time Frame: Baseline up to 4 weeks ]
  2. cleaved caspase-3 (CC3) as a marker of apoptosis [ Time Frame: Baseline up to 4 weeks ]
  3. c-reactive protein (CRP) as a marker of inflammation [ Time Frame: Baseline up to 4 weeks ]


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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03454529


Locations
United States, Michigan
Wayne State University/Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Michael S. Simon    313-576-8727      
Principal Investigator: Michael S. Simon, M.D., MPH         
Sub-Investigator: David Gorski, M.D., PhD.         
Sub-Investigator: Amy Weise, D.O.         
Sub-Investigator: Keiva L. Bland, M.D.         
Sub-Investigator: Lydia Choi, M.D.         
Sub-Investigator: Lawrence Flaherty, M.D.         
Sponsors and Collaborators
Michael Simon
National Cancer Institute (NCI)
Investigators
Principal Investigator: Michael Simon Barbara Ann Karmanos Cancer Institute

Responsible Party: Michael Simon, Principal Investigator, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT03454529     History of Changes
Other Study ID Numbers: 2017-073
NCI-2018-00044 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2017-073 ( Other Identifier: Wayne State University/Karmanos Cancer Institute )
P30CA022453 ( U.S. NIH Grant/Contract )
First Posted: March 6, 2018    Key Record Dates
Last Update Posted: March 6, 2018
Last Verified: March 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Simvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors