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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00637481
First received: March 17, 2008
Last updated: September 27, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Atypical Ductal Breast Hyperplasia
Breast Cancer
Ductal Breast Carcinoma in Situ
Lobular Breast Carcinoma in Situ
Drug: atorvastatin calcium
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Phase I Prevention Study of Atorvastatin in Women at Increased Risk for Breast Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Atorvastatin induced changes in proliferation rate measured by Ki-67 [ Time Frame: Baseline to 3 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Cytologic evaluation of FNA samples [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Proliferation and apoptosis analysis of FNA samples [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Proliferation and apoptosis analysis of FNA samples [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Inflammatory and lipid profile markers [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • Genotypic analysis [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Measurement of atorvastatin and its metabolites in serum and breast tissue [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]

Enrollment: 66
Study Start Date: March 2008
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (lower dose atorvastatin calcium)
Participants receive oral atorvastatin once daily for 3 months.
Drug: atorvastatin calcium
Given orally
Other Names:
  • CI-981
  • Lipitor
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II (atorvastatin calcium)
Participants receive oral atorvastatin (at a higher dose than in arm I) once daily for 3 months.
Drug: atorvastatin calcium
Given orally
Other Names:
  • CI-981
  • Lipitor
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm III (higher dose atorvastatin calcium)
Participants receive oral atorvastatin (at a higher dose than in arm II) once daily for 3 months.
Drug: atorvastatin calcium
Given orally
Other Names:
  • CI-981
  • Lipitor
Other: laboratory biomarker analysis
Correlative studies
Arm IV (no intervention)
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.
Other: laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   18 Years to 72 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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
  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: NCT00637481

Locations
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Principal Investigator: Banu Arun M.D. Anderson Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00637481     History of Changes
Other Study ID Numbers: NCI-2009-00859, NCI-2009-00859, CDR0000653466, 2006-0185, MDA05-6-01, N01CN35159
Study First Received: March 17, 2008
Last Updated: September 27, 2013
Health Authority: United States: Food and Drug Administration
United States: Federal Government

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma
Carcinoma in Situ
Carcinoma, Intraductal, Noninfiltrating
Hyperplasia
Carcinoma, Ductal, Breast
Carcinoma, Lobular
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Neoplasms, Ductal, Lobular, and Medullary
Pathologic Processes
Carcinoma, Ductal
Atorvastatin
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 August 18, 2014