MDACC Study Summary 2006-0185

Study Summary
No. 2006-0185:.......Breast......Banu Arun......Breast Medical Oncology

Study Summary Title



Study Summary Number:	2006-0185

Study Title:	Phase I prevention study of Atorvastatin in women at increased risk for breast cancer

Physician

New Patient Referral



Name:	Banu Arun	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Breast Medical Oncology	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-792-2817 Contact us about clinical trials

General Information



Disease Group:	Breast	Supported By:	N/A

Phase of Study:	Phase I	Return Visit:	Patients will come back at month three to be taken off study.

Treatment Agents:	Atorvastatin	Home Care:	All patients will take the atorvastatin as indicated (one 10 mg tablet, two 10 mg tablets, or four 10 mg tablets) every day for three months. All treatment may be given at home.

Treatment Loc:	Only at MDACC

Estimated Length of Stay in Houston:	N/A

Description/
Intervention:

The goal of this clinical research study is to find the smallest dose of
Lipitor (atorvastatin) that can be given to patients that may effect tumor
biomarkers in participants at risk for breast cancer. Biomarkers are certain
proteins in the blood that are related to breast cancer risk and the response
to certain drugs. The side effects of this drug will be studied, as well as
its effects on breast tissue and/or cancer risk.

Study Objectives / Outcomes

1. OBJECTIVES

Overall objective is to evaluate the chemopreventive potential of different doses of atorvastatin in a phase I chemoprevention study, by evaluating its biomarker modulatory efficacy. We propose to evaluate the modulation of biomarkers in response to different doses of atorvastatin in breast tissue of women who are at high risk for breast cancer

1.1

Primary Objective

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.

1.2. Secondary Objectives:

1) To evaluate atorvastatin induced modulation of breast cancer biomarkers markers (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.

2) To determine plasma and tissue levels of atorvastatin and two of its hydroxylated metabolites (o-hydroxyatorvastatin and p-hydroxyatorvastatin) in women who are treated with atorvastatin and to correlate these levels with Ki-67 levels

3) To correlate changes in Ki-67 and the above-described panel of biomarkers with HMG-CoA reductase genotype

Study Status Information



Study Activation / Registration Date:	03/19/2008

IRB Review and Approval Date:	02/16/2007

Study Type:	Phase I

Recruitment Status:	Open

Projected Accrual:	60

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) Women aged 18 -72 years 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.

2) 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.

3) 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.

4) ECOG performance status less than or = 1 (Karnofsky greater than or equal to 70%).

5) Participants must have normal organ and marrow function as defined below (up to 6 months prior to randomization): Leukocytes greater than 3,000/�L; Platelets greater than 100,000/�L; Total bilirubin within normal institutional limits; AST (SGOT) or/ALT (SGPT) </=1.5, institutional ULN; Creatinine within normal institutional limits; CPK, PTT, PT within normal institutional limits (up to 1 month prior to randomization).

6) 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:

1) Any type of active invasive cancer.

2) Bilateral mastectomy

3) 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.

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) 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.

8) 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.

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