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

NCT00637481 | Completed Phase 1

• 6 other identifiers: NCI-2009-00859CDR00006534662006-0185MDA05-6-01N01CN35159P30CA016672
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

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.

Conditions

Atypical Ductal Breast Hyperplasia; Breast Cancer; Ductal Breast Carcinoma in Situ; Lobular Breast Carcinoma in Situ

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline to 3 months

Secondary Outcomes (7)

• Cytologic evaluation of FNA samples

  Baseline

• Cytologic evaluation of FNA samples

  3 months

• Proliferation and apoptosis analysis of FNA samples

  Baseline

• Proliferation and apoptosis analysis of FNA samples

  3 months

• Inflammatory and lipid profile markers

  Up to 3 months

Study Arms (4)

Arm I (lower dose atorvastatin calcium)

EXPERIMENTAL

Participants receive oral atorvastatin once daily for 3 months.

Drug: atorvastatin calcium; Other: laboratory biomarker analysis

Arm II (atorvastatin calcium)

EXPERIMENTAL

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

Drug: atorvastatin calcium; Other: laboratory biomarker analysis

Arm III (higher dose atorvastatin calcium)

EXPERIMENTAL

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

Drug: atorvastatin calcium; Other: laboratory biomarker analysis

Arm IV (no intervention)

OTHER

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

Interventions

atorvastatin calcium DRUG

Given orally

Also known as: CI-981, Lipitor

Arm I (lower dose atorvastatin calcium); Arm II (atorvastatin calcium); Arm III (higher dose atorvastatin calcium)

laboratory biomarker analysis OTHER

Correlative studies

Arm I (lower dose atorvastatin calcium); Arm II (atorvastatin calcium); Arm III (higher dose atorvastatin calcium); Arm IV (no intervention)

Eligibility Criteria

• Age: 18 Years - 72 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Carcinoma, Intraductal, Noninfiltrating; Breast Neoplasms; Breast Carcinoma In Situ

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Carcinoma in Situ; Neoplasms, Ductal, Lobular, and Medullary; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• Banu Arun

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2008
• First Posted: March 18, 2008
• Study Start: March 1, 2008
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: December 29, 2016

Record last verified: 2016-12

Locations

US (1)