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

Primary Purpose

Atypical Ductal Breast Hyperplasia, Breast Cancer, Ductal Breast Carcinoma in Situ

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
atorvastatin calcium
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Atypical Ductal Breast Hyperplasia

Eligibility Criteria

18 Years - 72 Years (Adult, Older Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

  • Women at increased risk for breast cancer, defined by one of the following:

    • 5 year projected Gail risk of greater than 1.67%
    • Previous diagnosis of atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS) (per participating institution's pathology review), or ductal carcinoma in situ (participants could have received any type of surgery and radiation as long as they have an intact opposite breast)
  • The participant must have been properly informed of the study and must sign an informed consent to be able to be enrolled in the study; the informed consent document must be signed, witnessed, and dated prior to start of the study
  • Normal physical exam and bilateral mammogram that shows no evidence of suspicious, malignant disease, or uncharacterized lesions within last 12 months and no evidence of any active other cancer
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky greater than or equal to 70%)
  • Leukocytes greater than 3,000/uL
  • Platelets greater than 100,000/uL
  • Total bilirubin within normal institutional limits
  • AST (SGOT)or /ALT (SGPT) =< 1.5 X institutional ULN
  • Creatinine within normal institutional limits
  • CPK, PTT, PT within normal institutional limits (up to 1 month prior to randomization)
  • The effects of atorvastatin on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, women of child-bearing potential must agree to use adequate contraception (barrier method of birth control (IUD); abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately

Exclusion Criteria:

  • Any type of active invasive cancer
  • Bilateral mastectomy
  • Use of oral contraceptives; androgens; luteinizing-hormone-releasing-hormone (LHRH) analogs, prolactin inhibitors, antiandrogens, tamoxifen, raloxifen, or aromatase inhibitors; women who discontinue these drugs at least 3 months prior to study enrollment will be eligible
  • Chronic medical condition that requires regular use of statins or steroids (unless participants have discontinued these drugs 1 month prior to enrollment)
  • Participants may not be receiving any other investigational agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to atorvastatin
  • Psychiatric condition, including history of clinical depression, or addictive disorder that would preclude obtaining informed consent or would interfere with compliance; uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because atorvastatin is a Class X agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with atorvastatin breast feeding should be discontinued if the mother is treated with atorvastatin

Sites / Locations

  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Other

Arm Label

Arm I (lower dose atorvastatin calcium)

Arm II (atorvastatin calcium)

Arm III (higher dose atorvastatin calcium)

Arm IV (no intervention)

Arm Description

Participants receive oral atorvastatin once daily for 3 months.

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

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

Participants do not receive treatment. Participants undergo blood sample collection and fine needle aspiration of breast tissue at baseline and at 3 months for correlative biomarker studies.

Outcomes

Primary Outcome Measures

Atorvastatin induced changes in proliferation rate measured by Ki-67
A single proliferation rate at each time period is calculated for each participant based on the proportion cells expressing KI-67.

Secondary Outcome Measures

Cytologic evaluation of FNA samples
Cytologic evaluation of FNA samples
Proliferation and apoptosis analysis of FNA samples
Proliferation and apoptosis analysis of FNA samples
Inflammatory and lipid profile markers
Genotypic analysis
Measurement of atorvastatin and its metabolites in serum and breast tissue

Full Information

First Posted
March 17, 2008
Last Updated
December 28, 2016
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00637481
Brief Title
A Phase I Prevention Study of Atorvastatin in Women at Increased Risk for Breast Cancer
Official Title
A Phase I Prevention Study of Atorvastatin in Women at Increased Risk for Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
December 2016
Overall Recruitment Status
Completed
Study Start Date
March 2008 (undefined)
Primary Completion Date
October 2012 (Actual)
Study Completion Date
October 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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 Description
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 do not receive treatment. Participants undergo blood sample collection and fine needle aspiration of breast tissue at baseline and at 3 months for correlative biomarker studies.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atypical Ductal Breast Hyperplasia, Breast Cancer, Ductal Breast Carcinoma in Situ, Lobular Breast Carcinoma in Situ

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
66 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (lower dose atorvastatin calcium)
Arm Type
Experimental
Arm Description
Participants receive oral atorvastatin once daily for 3 months.
Arm Title
Arm II (atorvastatin calcium)
Arm Type
Experimental
Arm Description
Participants receive oral atorvastatin (at a higher dose than in arm I) once daily for 3 months.
Arm Title
Arm III (higher dose atorvastatin calcium)
Arm Type
Experimental
Arm Description
Participants receive oral atorvastatin (at a higher dose than in arm II) once daily for 3 months.
Arm Title
Arm IV (no intervention)
Arm Type
Other
Arm Description
Participants do not receive treatment. Participants undergo blood sample collection and fine needle aspiration of breast tissue at baseline and at 3 months for correlative biomarker studies.
Intervention Type
Drug
Intervention Name(s)
atorvastatin calcium
Other Intervention Name(s)
CI-981, Lipitor
Intervention Description
Given orally
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Atorvastatin induced changes in proliferation rate measured by Ki-67
Description
A single proliferation rate at each time period is calculated for each participant based on the proportion cells expressing KI-67.
Time Frame
Baseline to 3 months
Secondary Outcome Measure Information:
Title
Cytologic evaluation of FNA samples
Time Frame
Baseline
Title
Cytologic evaluation of FNA samples
Time Frame
3 months
Title
Proliferation and apoptosis analysis of FNA samples
Time Frame
Baseline
Title
Proliferation and apoptosis analysis of FNA samples
Time Frame
3 months
Title
Inflammatory and lipid profile markers
Time Frame
Up to 3 months
Title
Genotypic analysis
Time Frame
Baseline
Title
Measurement of atorvastatin and its metabolites in serum and breast tissue
Time Frame
Up to 3 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
72 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Women at increased risk for breast cancer, defined by one of the following: 5 year projected Gail risk of greater than 1.67% Previous diagnosis of atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS) (per participating institution's pathology review), or ductal carcinoma in situ (participants could have received any type of surgery and radiation as long as they have an intact opposite breast) The participant must have been properly informed of the study and must sign an informed consent to be able to be enrolled in the study; the informed consent document must be signed, witnessed, and dated prior to start of the study Normal physical exam and bilateral mammogram that shows no evidence of suspicious, malignant disease, or uncharacterized lesions within last 12 months and no evidence of any active other cancer Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky greater than or equal to 70%) Leukocytes greater than 3,000/uL Platelets greater than 100,000/uL Total bilirubin within normal institutional limits AST (SGOT)or /ALT (SGPT) =< 1.5 X institutional ULN Creatinine within normal institutional limits CPK, PTT, PT within normal institutional limits (up to 1 month prior to randomization) The effects of atorvastatin on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, women of child-bearing potential must agree to use adequate contraception (barrier method of birth control (IUD); abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately Exclusion Criteria: Any type of active invasive cancer Bilateral mastectomy Use of oral contraceptives; androgens; luteinizing-hormone-releasing-hormone (LHRH) analogs, prolactin inhibitors, antiandrogens, tamoxifen, raloxifen, or aromatase inhibitors; women who discontinue these drugs at least 3 months prior to study enrollment will be eligible Chronic medical condition that requires regular use of statins or steroids (unless participants have discontinued these drugs 1 month prior to enrollment) Participants may not be receiving any other investigational agents History of allergic reactions attributed to compounds of similar chemical or biologic composition to atorvastatin Psychiatric condition, including history of clinical depression, or addictive disorder that would preclude obtaining informed consent or would interfere with compliance; uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women are excluded from this study because atorvastatin is a Class X agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with atorvastatin breast feeding should be discontinued if the mother is treated with atorvastatin
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Banu Arun
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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