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
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: fluvastatin sodium
Procedure: Breast Cancer Surgery Only - Arm III
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized Phase II Biomarker Pilot Trial of Fluvastatin Use in Women With Ductal Carcinoma in Situ (DCIS) or Stage I Breast Cancer

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Change in proliferation after statin exposure, as measured by Ki-67 level [ Time Frame: up to 6 weeks ] [ Designated as safety issue: No ]

Secondary Outcome 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 [ 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 ]

Enrollment: 35
Study Start Date: July 2006
Study Completion Date: June 2011
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral fluvastatin sodium once daily for 3-6 weeks in the absence of disease progression or unacceptable toxicity.
Drug: fluvastatin sodium
Given orally
Experimental: Arm II
Patients receive oral fluvastatin sodium as in arm I at a higher dose.
Drug: fluvastatin sodium
Given orally
Experimental: Arm III
Patients do not receive fluvastatin sodium. breast Cancer surgery only
Procedure: Breast Cancer Surgery Only - Arm III
Breast Cancer Surgery

Detailed 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.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00416403

Locations
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Illinois
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115-6084
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
University of California, San Francisco
Investigators
Study Chair: Laura J. Esserman, MD, MBA University of California, San Francisco
  More Information

Additional Information:
Publications:
Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00416403     History of Changes
Other Study ID Numbers: CDR0000522934, UCSF-047522, UCSF-H8409-26206-01, MSKCC-06041
Study First Received: December 27, 2006
Last Updated: December 12, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, San Francisco:
breast cancer in situ
ductal breast carcinoma in situ
stage IA breast cancer
stage IB breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma
Carcinoma in Situ
Carcinoma, Ductal
Carcinoma, Ductal, Breast
Carcinoma, Intraductal, Noninfiltrating
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Neoplasms, Ductal, Lobular, and Medullary
Fluvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 30, 2014