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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00416403
First received: December 27, 2006
Last updated: December 12, 2012
Last verified: December 2012

December 27, 2006
December 12, 2012
July 2006
September 2007   (final data collection date for primary outcome measure)
Change in proliferation after statin exposure, as measured by Ki-67 level [ Time Frame: up to 6 weeks ] [ Designated as safety issue: No ]
Change in proliferation after statin exposure, as measured by Ki-67 level
Complete list of historical versions of study NCT00416403 on ClinicalTrials.gov Archive Site
  • 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 [ Time Frame: up to 6 weeks ] [ Designated as safety issue: No ]
  • Presence of comedo necrosis [ Time Frame: up to 6 weeks ] [ Designated as safety issue: No ]
  • Safety [ Time Frame: up to 6 weeks ] [ Designated as safety issue: Yes ]
  • 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
Not Provided
Not Provided
 
Effect of Fluvastatin on Biomarkers in Women Who Are Undergoing Surgery for Ductal Carcinoma In Situ or Stage I Breast Cancer
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.

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.

Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Breast Cancer
  • Drug: fluvastatin sodium
    Given orally
  • Procedure: Breast Cancer Surgery Only - Arm III
    Breast Cancer Surgery
  • Experimental: Arm I
    Patients receive oral fluvastatin sodium once daily for 3-6 weeks in the absence of disease progression or unacceptable toxicity.
    Intervention: Drug: fluvastatin sodium
  • Experimental: Arm II
    Patients receive oral fluvastatin sodium as in arm I at a higher dose.
    Intervention: Drug: fluvastatin sodium
  • Experimental: Arm III
    Patients do not receive fluvastatin sodium. breast Cancer surgery only
    Intervention: Procedure: Breast Cancer Surgery Only - Arm III
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. Breast Cancer Res Treat. 2010 Jan;119(1):137-44.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
35
June 2011
September 2007   (final data collection date for primary outcome measure)

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
Female
Not Provided
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00416403
CDR0000522934, UCSF-047522, UCSF-H8409-26206-01, MSKCC-06041
Yes
University of California, San Francisco
University of California, San Francisco
National Cancer Institute (NCI)
Study Chair: Laura J. Esserman, MD, MBA University of California, San Francisco
University of California, San Francisco
December 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP