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

Phase 2

Completed

• Conditions: Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage IIB Breast Cancer AJCC v6 and v7; Invasive Breast Carcinoma; Stage I Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7
• Interventions: Other: Laboratory Biomarker Analysis; Drug: Simvastatin

• Registration Number: NCT03454529
• Lead Sponsor: Michael Simon

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.

Study Timeline

• Study First Submitted: 2018-02-22
• Study First Submitted QC: 2018-03-02
• Study First Posted: 2018-03-06
• Study Start: 2018-03-09
• Primary Completion: 2021-10-06
• Study Completion: 2021-10-06
• Results First Submitted: 2023-04-17
• Status Verified: 2023-07
• Results First Submitted QC: 2023-07-27
• Last Update Submitted: 2023-07-27
• Results First Posted: 2023-08-01
• Last Update Posted: 2023-08-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 24

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (simvastatin)	Laboratory Biomarker Analysis	Patients receive simvastatin PO daily for 2-4 weeks in the absence of disease progression or unacceptable toxicity.
Treatment (simvastatin)	Simvastatin	Patients receive simvastatin PO daily for 2-4 weeks in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Change in Ki-67 Expression Assessed in Tumor Tissue by Immunohistochemistry	Baseline up to 4 weeks	Differences in % positive cells pre and post treatment along with 95% confidence interval

Trial Locations

Locations (1)

Wayne State University/Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States