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Atorvastatin in Preventing Breast Cancer in Women at Increased Risk for Breast Cancer
This study is currently recruiting participants.
Verified by M.D. Anderson Cancer Center, December 2009
First Received: March 17, 2008   Last Updated: December 9, 2009   History of Changes
Sponsor: M.D. Anderson Cancer Center
Collaborator: National Cancer Institute (NCI)
Information provided by: M.D. Anderson Cancer Center
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
Drug: Atorvastatin
Phase I

Study Type: Interventional
Study Design: Prevention, Randomized, Open Label, Single Group Assignment, Efficacy Study
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 M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Changes in proliferation as measured by Ki-67 at baseline and at 3 months [ Time Frame: 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 [ Time Frame: Baseline and at 3 months ] [ Designated as safety issue: No ]
  • Cytologic evaluation of fine needle aspiration (FNA) samples [ Time Frame: Baseline and at 3 months ] [ Designated as safety issue: No ]
  • Serum levels of LXR, total cholesterol, LDL, HDL, and C-reactive protein (CRP) [ Time Frame: 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 [ Time Frame: Baseline and at 3 months ] [ 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 [ Time Frame: Baseline and at 3 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 66
Study Start Date: March 2008
Estimated Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Group 1: No Intervention
Group 1 will not receive any atorvastatin.
Group 2: Experimental
10 mg atorvastatin every day
Drug: Atorvastatin

Group 2 = 10 mg atorvastatin every day

Group 3 = 20 mg atorvastatin every day

Group 4 = 40 mg atorvastatin every day

Group 3: Experimental
20 mg atorvastatin every day
Drug: Atorvastatin

Group 2 = 10 mg atorvastatin every day

Group 3 = 20 mg atorvastatin every day

Group 4 = 40 mg atorvastatin every day

Group 4: Experimental
40 mg atorvastatin every day
Drug: Atorvastatin

Group 2 = 10 mg atorvastatin every day

Group 3 = 20 mg atorvastatin every day

Group 4 = 40 mg atorvastatin every day


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

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/µL; Platelets greater than 100,000/µL; 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, 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. 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.
  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     713-792-3245        
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Banu Arun, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: UT MD Anderson Cancer Center ( Banu Arun, MD / Professor )
Study ID Numbers: 2006-0185, CDR0000588191, MDA-MDA05-6-01, MDA-2006-0185
Study First Received: March 17, 2008
Last Updated: December 9, 2009
ClinicalTrials.gov Identifier: NCT00637481     History of Changes
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
precancerous/nonmalignant condition
breast cancer
ductal breast carcinoma in situ
lobular breast carcinoma in situ
atypical ductal breast hyperplasia

Additional relevant MeSH terms:
Antimetabolites
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 February 08, 2010