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

Sponsor
Michael Simon (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT03454529
Collaborator
National Cancer Institute (NCI) (NIH)
24
Enrollment
1
Location
1
Arm
62.7
Anticipated Duration (Months)
0.4
Patients Per Site Per Month

Study Details

Study Description

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
Phase 2

Detailed Description

PRIMARY OBJECTIVES:

  1. 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.

  2. 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).

  3. 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 Design

Study Type:
Interventional
Actual Enrollment :
24 participants
Allocation:
N/A
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
Actual Study Start Date :
Mar 9, 2018
Actual Primary Completion Date :
Oct 6, 2021
Anticipated Study Completion Date :
May 31, 2023

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change in Ki-67 expression assessed in tumor tissue by immunohistochemistry [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 [Baseline up to 4 weeks]

    2. cleaved caspase-3 (CC3) as a marker of apoptosis [Baseline up to 4 weeks]

    3. c-reactive protein (CRP) as a marker of inflammation [Baseline up to 4 weeks]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    19 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Wayne State University/Karmanos Cancer Institute Detroit Michigan United States 48201

    Sponsors and Collaborators

    • Michael Simon
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Michael Simon, Barbara Ann Karmanos Cancer Institute

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Michael Simon, Principal Investigator, Barbara Ann Karmanos Cancer Institute
    ClinicalTrials.gov Identifier:
    NCT03454529
    Other Study ID Numbers:
    • 2017-073
    • NCI-2018-00044
    • 2017-073
    • P30CA022453
    First Posted:
    Mar 6, 2018
    Last Update Posted:
    Jun 23, 2022
    Last Verified:
    Jun 1, 2022
    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
    Simvastatin

    Study Results

    No Results Posted as of Jun 23, 2022