Phase II Trial - Breast Cancer Chemoprevention by Lovastatin

Breast Cancer Clinical Trial

Official title:

A Phase II Trial of Lovastatin for Modification of Abnormal Breast Duct Cytology and Risk-Associated Biomarkers in Women at High Inherited Risk of Breast Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00285857
• Other study ID #: BRSNSTU0010
• Secondary ID: BRSNSTU001095505
• Status: Terminated
• Phase: Phase 2
• First received: January 31, 2006
• Last updated: June 5, 2014
• Start date: November 2005
• Est. completion date: December 2010

Study information

• Verified date: June 2014
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to determine whether oral lovastatin, used for 6 months, results in a decrease of abnormal breast duct cytology in women at high inherited breast cancer risk.

Description:

The purpose of the study is to determine whether oral lovastatin, given daily at a dose of 80 mg for six months, results in a decrease in the rate of abnormal breast duct cytology (either hyperplasia or hyperplasia with atypia as measured by random periareolar fine needle aspiration (rpFNA) of breast duct cells) in women at high inherited breast cancer risk. A stratified analysis of this objective will be performed according to BRCA mutation status (absence or presence of an inherited deleterious BRCA1 or BRCA2 mutation).

Additional objectives of the study are:

• To assess change in mammographic density, which is known to associate with breast cancer risk, before and after treatment with lovastatin

• To assess incidence of breast cancers and new high-risk breast lesions, including atypical hyperplasia, ductal or lobular carcinoma in situ, or radial scar.

• To assess change in other breast cancer risk-associated biomarkers in rpFNA specimens, including:

• Ki-67 (a marker of cell proliferation)

• Estrogen receptor (ER)

• Progesterone receptor (PR)

• HER/2-neu over-expression

• Susceptibility to DNA damage

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. completion date: December 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Women with an increased inherited risk of breast cancer, but no current breast cancer. Defined by either:

• Known deleterious mutation in BRCA1, BRCA2, or other high-risk mutation

• Family history conveying at least a 2-fold increase in breast cancer risk

• Only those patients without evidence of abnormality requiring biopsy on mammography, breast MRI, or clinical breast examination will be eligible for inclusion.

• Patients must have ECOG performance status 0.

• Patients must have normal organ and marrow function, including complete blood count and comprehensive metabolic panel within normal institutional limits.

• Patients must have no evidence of active liver disease, or elevation of serum transaminases. Prior history of liver disease, if not currently active, will not exclude patients from participation. Patients must have no evidence of myopathy or myositis, including symptoms of generalized muscle aches or weakness, muscle tenderness, or elevation in creatine phosphokinase. In order to be eligible for participation, patients will be asked to limit alcoholic beverage consumption to three alcoholic drinks per week. This is specified because of recommendations for caution with use of lovastatin in patients with heavy alcohol use.

• Women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation. Only women who are not currently breastfeeding will be eligible to participate.

Exclusion Criteria:

• Patients with prior history of invasive breast cancer less than 2 years previously unless they had stage III or lower breast cancer more than 2 years ago.

• Patients with history of other cancer, excluding non-melanoma skin cancer, unless the cancer was stage III or lower, and they have been without evidence of recurrence for 5 years.

• Patients who show evidence of malignant cytology on initial rpFNA.

• Patients whose initial mammogram, breast MRI, or clinical breast exam prompts recommendation for biopsy by study investigators.

• Patients using other investigational agents.

• Use of tamoxifen or selective estrogen response modifiers (SERMS), including raloxifene; patients who have taken these agents within the last 2 years.

• Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to lovastatin.

• Patients with 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.

• Patients on concurrent lovastatin and cyclosporine, gemfibrozil, erythromycin, fibrates or niacin, unless they discontinue them.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Lovastatin
80 mg; 40 mg orally twice per day

Locations

Country	Name	City	State
United States	Stanford University Cancer Center	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Stanford University

Country where clinical trial is conducted

United States, 

References & Publications (1)

Vinayak S, Schwartz EJ, Jensen K, Lipson J, Alli E, McPherson L, Fernandez AM, Sharma VB, Staton A, Mills MA, Schackmann EA, Telli ML, Kardashian A, Ford JM, Kurian AW. A clinical trial of lovastatin for modification of biomarkers associated with breast c — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine whether oral lovastatin, given daily at a dose of 80 mg for six months, results in a decrease in the rate of abnormal breast duct cytology		6 months	No
Secondary	To assess change in mammographic density, which is known to associate with breast cancer risk, before and after treatment with lovastatin		6 months	No
Secondary	To assess incidence of breast cancers and new high-risk breast lesions, including atypical hyperplasia, ductal or lobular carcinoma in situ, or radial scar.		6 months	No
Secondary	To assess change in other breast cancer risk-associated biomarkers in rpFNA specimens.		6 months	No