Clinical Trial: A Phase I Prevention Study of Atorvastatin in Women at Increased Risk for Breast Cancer

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase I Prevention Study of Atorvastatin in Women at Increased Risk for Breast Cancer

Brief Summary: Chemoprevention is the use of certain drugs to keep cancer from forming. The use of atorvastatin (Lipitor) may prevent breast cancer. This randomized phase I trial is studying the best dose of atorvastatin in preventing breast cancer in women at increased risk for breast cancer.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the minimum biological effective dose (MBED) of atorvastatin required to induce modulation in the proliferation marker, Ki-67, in breast tissue of women who are at high risk to develop breast cancer. We will evaluate pre- and post atorvastatin treatment (4 dose levels) expression of Ki-67 in samples obtained via FNA from breast tissue of women at high risk for breast cancer. This specific aim tests the hypothesis that treatment with atorvastatin will induce a decrease in Ki-67.

SECONDARY OBJECTIVES:

I. To evaluate atorvastatin induced modulation of breast cancer biomarkers markers (EGFR, P-EGFR, ER, p21, p27, bcl-2, CC3, cytology) and drug related markers (LXR, total cholesterol, LDL, HDL, CRP) in women who are at high risk to develop breast cancer.

II. To determine plasma and tissue levels of atorvastatin and two of its hydroxylated metabolites (ohydroxyatorvastatin and p-hydroxyatorvastatin) in women who are treated with atorvastatin and to correlate these levels with Ki-67 levels. III. To correlate changes in Ki-67 and the above-described panel of biomarkers with HMG-CoA reductase genotype.

OUTLINE: Participants are randomized to 1 of 4 arms.

ARM I: Participants receive oral atorvastatin once daily for 3 months.

ARM II: Participants receive oral atorvastatin (at a higher dose than in arm I) once daily for 3 months.

ARM III: Participants receive oral atorvastatin (at a higher dose than in arm II) once daily for 3 months.

ARM IV: Participants
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Atorvastatin induced changes in proliferation rate measured by Ki-67 [ Time Frame: Baseline to 3 months ]

A single proliferation rate at each time period is calculated for each participant based on the proportion cells expressing KI-67.


Original Primary Outcome: Changes in proliferation as measured by Ki-67 at baseline and at 3 months

Current Secondary Outcome:

  • Cytologic evaluation of FNA samples [ Time Frame: Baseline ]
  • Cytologic evaluation of FNA samples [ Time Frame: 3 months ]
  • Proliferation and apoptosis analysis of FNA samples [ Time Frame: Baseline ]
  • Proliferation and apoptosis analysis of FNA samples [ Time Frame: 3 months ]
  • Inflammatory and lipid profile markers [ Time Frame: Up to 3 months ]
  • Genotypic analysis [ Time Frame: Baseline ]
  • Measurement of atorvastatin and its metabolites in serum and breast tissue [ Time Frame: Up to 3 months ]


Original Secondary Outcome:

  • Proliferation and apoptosis biomarker expression (EGFR, P-EGFR, ER, p21, p27, bcl-2, and CC3) as measured by immunohistochemistry at baseline and at 3 months
  • Cytologic evaluation of fine needle aspiration (FNA) samples at baseline and at 3 months
  • Serum levels of LXR, total cholesterol, LDL, HDL, and C-reactive protein (CRP) at baseline and at 3 months
  • Blood levels of HMG-CoA reductase genotype as measured by polymerase chain reaction at baseline
  • Serum and tissue levels of atorvastatin and its hydroxylated metabolites (o-hydroxyatorvastatin and p-hydroxyatorvastatin) as measured by tandem mass spectrometry at baseline and at 3 months


Information By: National Cancer Institute (NCI)

Dates:
Date Received: March 17, 2008
Date Started: March 2008
Date Completion:
Last Updated: December 28, 2016
Last Verified: December 2016