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Phase 2 Study of Lovastatin as Breast Cancer Chemoprevention

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ClinicalTrials.gov Identifier: NCT00285857
Recruitment Status : Terminated (Slow accrual)
First Posted : February 2, 2006
Results First Posted : March 9, 2017
Last Update Posted : March 9, 2017
Sponsor:
Information provided by (Responsible Party):
James Ford, Stanford University

Tracking Information
First Submitted Date  ICMJE January 31, 2006
First Posted Date  ICMJE February 2, 2006
Results First Submitted Date  ICMJE November 17, 2016
Results First Posted Date  ICMJE March 9, 2017
Last Update Posted Date March 9, 2017
Study Start Date  ICMJE November 2005
Actual Primary Completion Date May 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 19, 2017)
Change in the Incidence of Abnormal Breast Duct Cytology After Treatment With Lovastatin 80 mg/Day [ Time Frame: 6 months ]
Assessed on that basis of pre- and post-treatment evaluation with RPFNA (random periareolar fine needle aspiration). All subjects received a prescription for lovastatin 80 mg/day, to be taken as 40 mg twice-a-day. Cytology was qualitatively and quantitatively, using the Masood semiquantitative scale to assign a number to each specimen, with higher numbers indicating increasing degrees of abnormality, as follows: 06-10 Non-proliferative breast disease (NPBD) 11-14 Proliferative breast disease without atypia (PBD-A) 15-18 Proliferative breast disease with atypia (PBD+A) 19-24 Carcinoma in situ and invasive cancer (CIS/IC) If no cells could be obtained after multiple RPFNA attempts, the classification was acellular. Change from NPBD to PBD-A was considered Unfavorable. Change from NPBD to Acellular was considered Equivocal. Change from PBD-A to NPBD was considered Favorable.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 19, 2017)
  • Change in Mammographic Density Before and After Treatment With Lovastatin 80 mg/Day [ Time Frame: 6 months ]
    Bilateral mammography was performed at study entry (before lovastatin therapy) and at study conclusion (after lovastatin therapy) . Mammograms were assessed for a decline in mean breast density, using the American College of Radiology Breast Imaging Reporting and Data System (BI-RAD) composition system for mammographic density assessment. Category 0 Need additional imaging evaluation
    1. Negative
    2. Benign
    3. Probably benign
    4. Suspicious abnormality
    5. Highly suggestive of malignancy
    6. Known biopsy-proven malignancy
  • Change in Total Cholesterol After Treatment With Lovastatin 80 mg/Day [ Time Frame: 6 months ]
  • Change in Low Density Lipoprotein (LDL) After Treatment With Lovastatin 80 mg/Day [ Time Frame: 6 months ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 2 Study of Lovastatin as Breast Cancer Chemoprevention
Official Title  ICMJE A Phase 2 Trial of Lovastatin for Modification of Abnormal Breast Duct Cytology and Risk-Associated Biomarkers in Women at High Inherited Risk of Breast Cancer
Brief Summary The study evaluates if a 6-month course of oral lovastatin at 80 mg/day would decrease abnormal breast duct cytology in women with a high inherited breast cancer risk.
Detailed Description

The study evaluates if a 6-month course of oral lovastatin at 80 mg/day (as 40 mg twice-a-day) would decrease abnormal breast duct cytology in women with a high inherited breast cancer risk. Breast duct cytology was assessed as hyperplasia or hyperplasia with atypia, as measured by random periareolar fine needle aspiration (rpFNA), of breast duct cells.

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
  • Asess incidence of breast cancers and new high-risk breast lesions, including atypical hyperplasia, ductal or lobular carcinoma in situ, or radial scar.
  • 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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE Drug: Lovastatin

Lovastatin 80 mg/day as 40 mg orally twice daily.

Lovastatin is approved by FDA as a cholesterol-lowering agent.

Other Names:
  • Mevacor
  • Advicor (as a combination with niacin)
  • Altocor
  • Altoprev
  • Statosan (Atos Pharma)
Study Arms  ICMJE Experimental: Lovastatin 80 mg/day
Lovastatin 80 mg/day as 40 mg orally twice daily, for 6 months.
Intervention: Drug: Lovastatin
Publications * 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 cancer risk. Breast Cancer Res Treat. 2013 Nov;142(2):389-98. doi: 10.1007/s10549-013-2739-z. Epub 2013 Oct 29.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: June 5, 2014)
30
Original Enrollment  ICMJE
 (submitted: January 31, 2006)
57
Actual Study Completion Date  ICMJE December 2010
Actual Primary Completion Date May 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

INCLUSION CRITERIA

  • Female
  • Increased inherited risk of breast cancer, as defined by:

    • Known deleterious mutation in BRCA1, BRCA2, or other high-risk mutation
    • Family history conveying at least a 2-fold increase in breast cancer risk
  • ECOG performance status 0
  • Normal organ and marrow function, including complete blood count and comprehensive metabolic panel within normal institutional limits
  • Subject agreement to limit alcoholic beverage consumption to three alcoholic drinks per week.

EXCLUSION CRITERIA

  • Prior history of invasive breast cancer less than 2 years previously (EXCEPTION: stage III or lower breast cancer > 2 years ago)
  • Current or history of other cancers (EXCEPTION: non-melanoma skin cancer, or stage III or cancer without evidence of recurrence for 5 years
  • Initial mammogram, breast MRI, or clinical breast examination prompts recommendation for biopsy by study investigators.
  • Evidence of malignant cytology on initial rpFNA.
  • Use of other investigational agents.
  • Use of tamoxifen or selective estrogen response modifiers (SERMS), including raloxifene, within the last 2 years.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to lovastatin.
  • 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.
  • Currently receiving lovastatin and cyclosporine, gemfibrozil, erythromycin, fibrates or niacin, (unless discontinued for study participation)
  • No evidence of active liver disease, nor elevation of serum transaminases (prior history of liver disease, if not currently active, is not an exclusion)
  • No evidence of myopathy or myositis, including symptoms of generalized muscle aches or weakness, muscle tenderness, or elevation in creatine phosphokinase.
  • Lactating (breastfeeding)
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00285857
Other Study ID Numbers  ICMJE IRB-13732
BRSNSTU0010 ( Other Identifier: OnCore )
95505 ( Other Identifier: Stanford University Alternate IRB Approval Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party James Ford, Stanford University
Study Sponsor  ICMJE Stanford University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: James Ford, MD Stanford University
PRS Account Stanford University
Verification Date January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP