Atorvastatin in Preventing Breast Cancer in Women at Increased Risk for Breast Cancer

Condition(s) targeted: Breast Cancer

Intervention: Atorvastatin (Drug)

Phase: Phase 1

Status: Recruiting

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Banu Arun, MD, Principal Investigator, Affiliation: M.D. Anderson Cancer Center

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming. The use of atorvastatin (Lipitor) may prevent breast cancer.

PURPOSE: This randomized phase I trial is studying the best dose of atorvastatin in preventing breast cancer 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 design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Primary outcome: Changes in Ki-67

Detailed description: OBJECTIVES:

Primary

- 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 for developing breast cancer.

Secondary

- To evaluate atorvastatin-induced modulation of breast cancer biomarkers (EGFR, P-EGFR,

ER, p21, p27, bcl-2, CC3, and cytology) and drug-related markers (LXR, total cholesterol, LDL, HDL, CRP) in these participants.

- To determine plasma and tissue levels of atorvastatin and its hydroxylated metabolites

(o-hydroxyatorvastatin and p-hydroxyatorvastatin) and correlate these levels with Ki-67 levels.

- 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.

Minimum age: 18 Years. Maximum age: 72 Years. Gender(s): Female.

Criteria:

Inclusion Criteria:

1. Increased risk for breast cancer, defined by one of the following: - Greater than or

equal to 20% life long risk by Claus, Tyrer-Cuzick, BOADICEA, or BRCAPRO model, or a

5 year projected Gail risk of greater than or equal to 1. 67%; - Previous diagnosis of

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).

2. Woman, age 18-72 years

3. 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 and dated prior to start of the study. No witnesses are required.

4. Normal physical exam, including a normal clinical breast examination, and mammogram that shows no evidence of suspicious, malignant disease, or uncharacterized lesions within last 12 months and no evidence of any active invasive cancer. (For abnormal mammogram, if follow up tests such as ultrasound or biopsy shows no evidence of suspicious, malignant disease, or uncharacterized lesions within last 12 months, patients will be allowed on the study).

5. ECOG performance status 6. Participants must have normal organ and marrow function as defined below (up to 6 months prior to randomization): Leukocytes greater than 3,000/mL; Platelets greater than 100,000/mL; Total bilirubin within normal institutional limits; AST (SGOT) /ALT (SGPT) 1. 5 X institutional ULN; Creatinine within normal institutional upper limits; CPK, PTT, PT within normal institutional upper limits (up to 1 month prior to randomization).

7. 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.

8. If the participant is of childbearing potential, she must have a documented negative urine pregnancy test within 14 days prior to randomization or start of the study agent.

9. Normal bimanual pelvic examination within the last 12 months and any normal pap smear within the last 3 years (or more often at the gynecologist's discretion) that show no invasive cancer. Patients with total hysterectomy do not need to have pap smear.

Exclusion Criteria:

1. Any type of active invasive cancer.

2. Bilateral mastectomy

3. Oral or injection use of contraceptives; androgens; luteinizing-hormone-releasing- hormone (LHRH) analogs, prolactin inhibitors, antiandrogens, tamoxifen, raloxifene, or aromatase inhibitors. Women who discontinue these drugs at least 3 months prior to study enrollment will be eligible.

4. Chronic medical condition that requires regular use of statins or steroids (unless participants have discontinued these drugs 1 month prior to enrollment).

5. Participants may not be receiving any other investigational agents.

6. History of allergic reactions attributed to compounds of similar chemical or biologic composition to atorvastatin.

7. Uncontrolled psychiatric condition, including history of clinical depression, or addictive disorder that would preclude obtaining informed consent or would interfere with compliance.

8. 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.

9. Breast implantation

10. 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.

M. D. Anderson Cancer Center at University of Texas, Houston, Texas 77030-4009, United States; Recruiting
Clinical Trials Office - M. D. Anderson Cancer Center, Phone: 713-792-3245

Clinical trial summary from the National Cancer Institute's PDQ® database

UT MD Anderson Cancer Center website

Starting date: March 2008
Last updated: October 6, 2011