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

University of California San Francisco (UCSF)

Status and phase: Completed; Phase 2

Conditions: Breast Cancer

Treatments: Drug: fluvastatin sodium; Procedure: Breast Cancer Surgery Only - Arm III

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00416403

UCSF-H8409-26206-01

CDR0000522934

UCSF-047522

MSKCC-06041

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 35 patients

Sex: Female

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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35 participants in 3 patient groups

Arm I

Experimental group

Description:

Patients receive oral fluvastatin sodium once daily for 3-6 weeks in the absence of disease progression or unacceptable toxicity.

Treatment:

Drug: fluvastatin sodium

Arm II

Experimental group

Description:

Patients receive oral fluvastatin sodium as in arm I at a higher dose.

Treatment:

Drug: fluvastatin sodium

Arm III

Experimental group

Description:

Patients do not receive fluvastatin sodium. breast Cancer surgery only

Treatment:

Procedure: Breast Cancer Surgery Only - Arm III