Atorvastatin in Preventing Breast Cancer in Women at Increased Risk for Breast Cancer - Full Text View

Sponsor:	M.D. Anderson Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00637481

Purpose

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming. The use of atorvastatin 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.

Condition	Intervention	Phase
Breast Cancer Precancerous/Nonmalignant Condition	Drug: atorvastatin calcium Genetic: polymerase chain reaction Other: cytologic test Other: immunohistochemistry staining method Other: laboratory biomarker analysis Other: mass spectrometry Procedure: fine-needle aspiration	Phase I

Study Type:	Interventional
Study Design:	Prevention, Randomized, Active Control
Official Title:	A Phase I Prevention Study of Atorvastatin in Women at Increased Risk for Breast Cancer

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Atorvastatin Atorvastatin calcium

U.S. FDA Resources

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

Primary Outcome Measures:

Changes in proliferation as measured by Ki-67 at baseline and at 3 months [ Designated as safety issue: No ]

Secondary Outcome Measures:

Proliferation and apoptosis biomarker expression (EGFR, P-EGFR, ER, p21, p27, bcl-2, and CC3) as measured by immunohistochemistry at baseline and at 3 months [ Designated as safety issue: No ]
Cytologic evaluation of fine needle aspiration (FNA) samples at baseline and at 3 months [ Designated as safety issue: No ]
Serum levels of LXR, total cholesterol, LDL, HDL, and C-reactive protein (CRP) at baseline and at 3 months [ Designated as safety issue: No ]
Blood levels of HMG-CoA reductase genotype as measured by polymerase chain reaction at baseline [ Designated as safety issue: No ]
Serum and tissue levels of atorvastatin and its hydroxylated metabolites (o-hydroxyatorvastatin and p-hydroxyatorvastatin) as measured by tandem mass spectrometry at baseline and at 3 months [ Designated as safety issue: No ]

Estimated Enrollment:	66
Study Start Date:	March 2008
Estimated Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study:	18 Years to 72 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

At increased risk for breast cancer, defined by one of the following criteria:
- 5-year projected Gail risk of developing breast cancer > 1.67%
- Prior diagnosis of atypical hyperplasia (AH), lobular carcinoma in situ (LCIS), or ductal carcinoma in situ (DCIS)
  - Participants may have received any type of surgery and radiotherapy as long as they have an intact opposite breast
No evidence of suspicious, malignant disease or uncharacterized lesions by physical exam and bilateral mammogram within the past 12 months
No evidence of any other active invasive cancer

PATIENT CHARACTERISTICS:

ECOG performance status (PS) 0 or 1 (Karnofsky PS 70-100%)
Leukocytes > 3,000/μL
Platelet count > 100,000/μL
Total bilirubin normal
AST/ALT ≤ 1.5 times upper limit of normal
Creatinine normal
Creatine phosphokinase (CPK) normal
PTT and PT normal
Not pregnant or nursing
Negative pregnancy test
Fertile participants must use effective contraception
No concurrent uncontrolled illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness/social situation that would preclude compliance with study requirements
No chronic medical condition that requires regular use of statins or steroids
No history of allergic reactions attributed to compounds of similar chemical or biologic composition to atorvastatin
No psychiatric condition, including history of clinical depression, or addictive disorder that would preclude giving informed consent or would preclude study compliance

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior bilateral mastectomy
More than 3 months since prior oral contraceptives, androgens, luteinizing hormone-releasing hormone (LHRH) analogs, prolactin inhibitors, antiandrogens, tamoxifen, raloxifene, or aromatase inhibitors
More than 1 month since prior statins or steroids
No other concurrent investigational agents

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00637481

Locations

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

Sponsors and Collaborators

M.D. Anderson Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Banu Arun, MD

M.D. Anderson Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000588191, MDA-MDA05-6-01, MDA-2006-0185
Study First Received:	March 17, 2008
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00637481 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

breast cancer
ductal breast carcinoma in situ
lobular breast carcinoma in situ
atypical ductal breast hyperplasia

Additional relevant MeSH terms:

Antimetabolites
Precancerous Conditions
Skin Diseases
Molecular Mechanisms of Pharmacological Action
Antilipemic Agents
Breast Neoplasms
Enzyme Inhibitors
Anticholesteremic Agents

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Therapeutic Uses
Breast Diseases
Atorvastatin

ClinicalTrials.gov processed this record on November 20, 2009