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

December 12, 2012 updated by: University of California, San Francisco

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 Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

35

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94115
        • UCSF Helen Diller Family Comprehensive Cancer Center
    • Illinois
      • Chicago, Illinois, United States, 60637-1470
        • University of Chicago Cancer Research Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115-6084
        • Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change in proliferation after statin exposure, as measured by Ki-67 level
Time Frame: up to 6 weeks
up to 6 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
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
up to 6 weeks
Presence of comedo necrosis
Time Frame: up to 6 weeks
up to 6 weeks
Safety
Time Frame: up to 6 weeks
up to 6 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Laura J. Esserman, MD, MBA, University of California, San Francisco

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2006

Primary Completion (Actual)

September 1, 2007

Study Completion (Actual)

June 1, 2011

Study Registration Dates

First Submitted

December 27, 2006

First Submitted That Met QC Criteria

December 27, 2006

First Posted (Estimate)

December 28, 2006

Study Record Updates

Last Update Posted (Estimate)

December 13, 2012

Last Update Submitted That Met QC Criteria

December 12, 2012

Last Verified

December 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000522934
  • UCSF-047522
  • UCSF-H8409-26206-01
  • MSKCC-06041

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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