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

NCT ID: NCT03454529

Last Updated: 2023-08-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-09
• Study Completion Date: 2021-10-06

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.

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (simvastatin)

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

Group Type: EXPERIMENTAL

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Simvastatin

Intervention Type: DRUG

Given PO

Interventions

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Simvastatin

Given PO

Intervention Type: DRUG

Other Intervention Names

MK 733; Synvinolin; Zocor

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

• Minimum Eligible Age: 19 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Michael Simon

OTHER

Sponsor Role: lead

Responsible Party

Michael Simon

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Michael Simon

Role: PRINCIPAL_INVESTIGATOR

Barbara Ann Karmanos Cancer Institute

Locations

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States

Countries

United States

References

Asari K, Sun WT, Kok ZH, Lam YH, Ng BL, Saunders V, White DL, Chuah C, Xiang W. Simvastatin enhances the efficacy of nilotinib in chronic myeloid leukaemia by post-translational modification and drug transporter modulation. Anticancer Drugs. 2021 Jun 1;32(5):526-536. doi: 10.1097/CAD.0000000000001028.

Reference Type: DERIVED

PMID: 33587350 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2018-00044

Identifier Type: REGISTRY

Identifier Source: secondary_id

2017-073

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA022453

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2017-073

Identifier Type: -

Identifier Source: org_study_id