Effect of Fluvastatin on Biomarkers in Women Who Are Undergoing Surgery for Ductal Carcinoma In Situ or Stage I Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Collecting samples of blood and tissue from patients with cancer to study in the laboratory may help doctors learn how fluvastatin effects biomarkers related to breast cancer. PURPOSE: This randomized phase II trial is studying how fluvastatin effects biomarkers in women undergoing surgery for ductal carcinoma in situ or stage I breast cancer.

Detailed Description
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OBJECTIVES: Primary Determine differences between measures of cell proliferation (Ki-67) in women with ductal carcinoma in situ (DCIS) or stage I breast cancer receiving neoadjuvant fluvastatin sodium. Secondary Determine whether statin use differentially affects specific types of DCIS/early-stage breast cancer (comedo, estrogen receptor [ER]-positive, ER-negative). Compare differences between tissue staining of CD68, circulating macrophages, and regulatory T cells in these patients. Assess the feasibility of using inherent susceptibility (mRNA polymerase chain reaction testing) to predict response to statins in these patients. OUTLINE: This is a randomized, controlled, single-blind, multicenter, pilot study. Patients are randomized to 1 of 2 treatment arms (arms I or II). Patients accrued as control participants are assigned to arm III. Arm I: Patients receive oral fluvastatin sodium once daily for 3-6 weeks in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive oral fluvastatin sodium as in arm I at a higher dose. Arm III (control): Patients do not receive fluvastatin sodium. All patients then undergo definitive surgery. Patients in arms I and II undergo blood collection at baseline and at the time of surgery for biomarker analysis. Patients in arm III undergo blood collection at baseline and then approximately 1 month later. Tissue is collected from patients in all arms at the time of surgery. Blood and tissue samples are examined for biological markers, including Ki-67, C-reactive protein, cleaved caspase 3, HER2, CD68 gene, and estrogen and progesterone receptors by immunohistochemistry. Markers of inflammation (e.g., comedo necrosis macrophages and CD25-positive T cells), low-density lipoprotein, and cholesterol are also analyzed. Serum mRNA is measured by polymerase chain reaction. PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

Official Title
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Randomized Phase II Biomarker Pilot Trial of Fluvastatin Use in Women With Ductal Carcinoma in Situ (DCIS) or Stage I Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: fluvastatin sodium
* Procedure: Breast Cancer Surgery Only - Arm III


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed ductal carcinoma in situ (DCIS) or stage I breast cancer by stereotactic core or incisional biopsy Planning to undergo surgery in 3-6 weeks Patients undergoing re-excision due to evidence of tumor present at surgical margins are eligible Hormone receptor status not specified PATIENT CHARACTERISTICS: Female Menopausal status not specified ALT and AST ≤ 10% above upper limit of normal Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Able to tolerate statins Willing to undergo 2 blood draws (separated by approximately 3-4 weeks) during study participation (control arm) PRIOR CONCURRENT THERAPY: No other concurrent statins No concurrent chemotherapy No concurrent administration of any of the following: Niacin Propranolol Cholestyramine Cyclosporine Digoxin Erythromycin Itraconazole Gemfibrozil Phenytoin Diclofenac Tolbutamide Glyburide Losartan Cimetidine Ranitidine Omeprazole Rifampin Warfarin No initiation of new hormonal therapy during study participation Concurrent participation in other clinical trials (e.g., for DCIS or prevention) is allowed
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive oral fluvastatin sodium once daily for 3-6 weeks in the absence of disease progression or unacceptable toxicity. | Drug: fluvastatin sodium<br>* Given orally<br>|
| Experimental: Arm II<br>Patients receive oral fluvastatin sodium as in arm I at a higher dose. | Drug: fluvastatin sodium<br>* Given orally<br>|
| Experimental: Arm III<br>Patients do not receive fluvastatin sodium. breast Cancer surgery only | Procedure: Breast Cancer Surgery Only - Arm III<br>* Breast Cancer Surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in proliferation after statin exposure, as measured by Ki-67 level |  | up to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood and serum markers, including C-reactive protein, cleaved caspase 3, HER2, CD68, macrophages and immunoregulatory CD25 T cells, estrogen and progesterone receptors, mRNA, low-density lipoprotein, and cholesterol |  | up to 6 weeks | 
| Presence of comedo necrosis |  | up to 6 weeks | 
| Safety |  | up to 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer in situ, ductal breast carcinoma in situ, stage IA breast cancer, stage IB breast cancer