- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03454529
The Effect of Simvastatin on Breast Cancer Cell Growth in Women With Stage I-II Breast Cancer
The Effect of Statins on Markers of Breast Cancer Proliferation and Apoptosis in Women With Early Stage Breast Cancer
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Michigan
-
Detroit, Michigan, United States, 48201
- Wayne State University/Karmanos Cancer Institute
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (simvastatin)
Patients receive simvastatin PO daily for 2-4 weeks in the absence of disease progression or unacceptable toxicity.
|
Correlative studies
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Ki-67 Expression Assessed in Tumor Tissue by Immunohistochemistry
Time Frame: Baseline up to 4 weeks
|
Differences in % positive cells pre and post treatment along with 95% confidence interval
|
Baseline up to 4 weeks
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Percentage of Cells P27+ From Pre-treatment to Post-treatment
Time Frame: Baseline up to 4 weeks
|
The difference in percentage of cells P27+ from pre-treatment to post-treatment
|
Baseline up to 4 weeks
|
Cleaved Caspase-3 (CC3) as a Marker of Apoptosis
Time Frame: Baseline up to 4 weeks
|
The difference in (percentage of cells cleaved caspase-3 (CC3)+) from pre-treatment to post-treatment
|
Baseline up to 4 weeks
|
C-reactive Protein (CRP) as a Marker of Inflammation
Time Frame: Baseline up to 4 weeks
|
c-reactive protein (CRP) as a marker of inflammation.
|
Baseline up to 4 weeks
|
Change in (% Intracellular p27 +) From Pre-treatment to Post-treatment
Time Frame: Baseline up to 4 weeks
|
the difference in (% intracellular p27 +) from pre-treatment to post-treatment
|
Baseline up to 4 weeks
|
Changes in p27 Cytoplasmic Intensity
Time Frame: Baseline up to 4 weeks
|
the difference in (p27 cytoplasmic intensity) from pre-treatment to post-treatment
|
Baseline up to 4 weeks
|
Changes in Cyclin D1
Time Frame: Baseline up to 4 weeks
|
the difference in % cyclin D1+ stained out of total cells from pre-treatment to post-treatment;
|
Baseline up to 4 weeks
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Michael Simon, Barbara Ann Karmanos Cancer Institute
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2017-073 (Other Identifier: Wayne State University/Karmanos Cancer Institute)
- P30CA022453 (U.S. NIH Grant/Contract)
- NCI-2018-00044 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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