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

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Single Blind, Active Control

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.

Intervention(s) in this Clinical Trial

• Drug: fluvastatin sodium
  • Given orally
• Procedure: observation
  • Patients do not receive fluvastatin sodium.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Arm I
  • Patients receive oral fluvastatin sodium once daily for 3-6 weeks in the absence of disease progression or unacceptable toxicity.
• Experimental: Arm II
  • Patients receive oral fluvastatin sodium as in arm I at a higher dose.
• No Intervention: Arm III
  • Patients do not receive fluvastatin sodium.

Primary Measures

• Change in proliferation after statin exposure, as measured by Ki-67 level
  • Safety Issue?: No

Secondary Measures

• 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
  • Safety Issue?: No
• Presence of comedo necrosis
  • Safety Issue?: No
• Safety
  • Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Memorial Sloan-Kettering Cancer Center

Overall Clinical Trial Officials and Contacts

Laura J. Esserman, MD, MBA Study Chair UCSF Helen Diller Family Comprehensive Cancer Center  

Information obtained from ClinicalTrials.gov on October 06, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00416403

Study ID Number: CDR0000522934

ClinicalTrials.gov Identifier: NCT00416403

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database