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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00416403
• Other study ID #: CDR0000522934
• Secondary ID: UCSF-047522UCSF-
• Status: Completed
• Phase: Phase 2
• First received: December 27, 2006
• Last updated: December 12, 2012
• Start date: July 2006
• Est. completion date: June 2011

Study information

• Verified date: December 2012
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: June 2011
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Carcinoma in Situ
• Carcinoma, Ductal
• Carcinoma, Intraductal, Noninfiltrating

Intervention

Drug:
• fluvastatin sodium
Given orally

Procedure:
• Breast Cancer Surgery Only - Arm III
Breast Cancer Surgery

Locations

Country	Name	City	State
United States	Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute	Boston	Massachusetts
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Garwood ER, Kumar AS, Baehner FL, Moore DH, Au A, Hylton N, Flowers CI, Garber J, Lesnikoski BA, Hwang ES, Olopade O, Port ER, Campbell M, Esserman LJ. Fluvastatin reduces proliferation and increases apoptosis in women with high grade breast cancer. Breas — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in proliferation after statin exposure, as measured by Ki-67 level		up to 6 weeks	No
Secondary	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	No
Secondary	Presence of comedo necrosis		up to 6 weeks	No
Secondary	Safety		up to 6 weeks	Yes