Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Biomarker/Laboratory analysis, Treatment Active Not specified NCI UCSF-047522 UCSF-H8409-26206-01, MSKCC-06041, NCT00416403

Objectives

Primary

1. 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

1. Determine whether statin use differentially affects specific types of DCIS/early-stage breast cancer (comedo, estrogen receptor [ER]-positive, ER-negative).
2. Compare differences between tissue staining of CD68, circulating macrophages, and regulatory T cells in these patients.
3. Assess the feasibility of using inherent susceptibility (mRNA polymerase chain reaction testing) to predict response to statins in these patients.

Entry 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

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

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)

Expected Enrollment

A total of 60 patients will be accrued for this study.

Outcomes

Change in proliferation after statin exposure, as measured by Ki-67 level

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
Presence of comedo necrosis
Safety

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.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Laura Esserman, MD, MBA, Protocol chair		Ph: 415-885-7691; 800-888-8664

U.S.A.
California
	San Francisco
	UCSF Helen Diller Family Comprehensive Cancer Center
		Clinical Trials Office - UCSF Helen Diller Family Comprehensive Cancer Center	Ph:  877-827-3222
Illinois
	Chicago
	University of Chicago Cancer Research Center
		Olufunmilayo I. Falusi Olopade, MD, FACP	Ph:  773-702-6149
Massachusetts
	Boston
	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
		Judy Garber, MD	Ph:  617-632-2282 866-790-4500
			Email: judy_garber@dfci.harvard.edu
New York
	New York
	Memorial Sloan-Kettering Cancer Center
		Elisa Rush Port, MD	Ph:  212-639-5461 800-525-2225
			Email: porte@mskcc.org

Registry Information
Official Title		Randomized Phase II Biomarker Pilot Trial of Fluvastatin Use in Women with Ductal Carcinoma in Situ (DCIS) or Stage I Breast Cancer
Trial Start Date		2006-07-11
Registered in ClinicalTrials.gov		NCT00416403
Date Submitted to PDQ		2006-11-15
Information Last Verified		2007-05-27
NCI Grant/Contract Number		CA08748

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