Phase II Trial - Breast Cancer Chemoprevention by Lovastatin

This study has been terminated.
(Slow accrual)
Sponsor:
Information provided by (Responsible Party):
James Ford, Stanford University
ClinicalTrials.gov Identifier:
NCT00285857
First received: January 31, 2006
Last updated: June 5, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: Lovastatin
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • 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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To assess change in mammographic density, which is known to associate with breast cancer risk, before and after treatment with lovastatin [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • To assess incidence of breast cancers and new high-risk breast lesions, including atypical hyperplasia, ductal or lobular carcinoma in situ, or radial scar. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • To assess change in other breast cancer risk-associated biomarkers in rpFNA specimens. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: November 2005
Study Completion Date: December 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: lovastatin Drug: Lovastatin
80 mg; 40 mg orally twice per day
Other Names:
  • Mevacor
  • Advicor (as a combination with niacin)
  • Altocor
  • Altoprev
  • Statosan (Atos Pharma)

Detailed 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
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00285857

Locations
United States, California
Stanford University Cancer Center
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: James Ford, MD Stanford University
  More Information

Publications:
Responsible Party: James Ford, Associate Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT00285857     History of Changes
Other Study ID Numbers: BRSNSTU0010, BRSNSTU0010, 95505
Study First Received: January 31, 2006
Last Updated: June 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Stanford University:
breast cancer
lovastatin
duct cytology

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Lovastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 28, 2014