Invasive Breast CarcinomaPhase 2NCT03454529
The Effect of Simvastatin on Breast Cancer Cell Growth in Women With Stage I-II Breast Cancer
A Phase 2 study testing Laboratory Biomarker Analysis and Simvastatin in people with Invasive Breast Carcinoma and Stage I Breast Cancer AJCC v7, run by Michael Simon at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 years and older, women only
- Conditions the study is for
- Invasive Breast Carcinoma, Stage I Breast Cancer AJCC v7, Stage IA Breast Cancer AJCC v7
- What is being tested?
- Laboratory Biomarker Analysis and Simvastatin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Mar 2018to 6 Oct 2021
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 20Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
About this study
Official title: The Effect of Statins on Markers of Breast Cancer Proliferation and Apoptosis in Women With Early Stage Breast Cancer
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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
- 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
- Being tested
- Laboratory Biomarker Analysis, Simvastatin
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
SimvastatinDrug
Also called MK 733, Synvinolin, Zocor
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (simvastatin) | Experimental | Patients receive simvastatin PO daily for 2-4 weeks in the absence of disease progression or unacceptable toxicity. Receives: Other: Laboratory Biomarker Analysis; Drug: Simvastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Ki-67 Expression Assessed in Tumor Tissue by Immunohistochemistry
Differences in % positive cells pre and post treatment along with 95% confidence interval
Measured: Baseline up to 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2018
- Study start9 Mar 2018
- Primary completion6 Oct 2021
- Study completion6 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Invasive Breast CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Michael Simon
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, Michael Simon, Barbara Ann Karmanos Cancer Institute
- Investigators
- Michael Simon, Principal investigator, Barbara Ann Karmanos Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03454529
- Sponsor's protocol ID
- 2017-073
- Other IDs
- NCI-2018-00044, 2017-073, P30CA022453
- Status last verified
- Jul 2023
- First submitted
- 22 Feb 2018
- Last updated
- 1 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 33587350