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Study of Breast Cancer Prevention by Letrozole in High Risk Women

Primary Purpose

Breast Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Letrozole
Placebo
Sponsored by
Carol Fabian, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Breast Cancer

Eligibility Criteria

30 Years - 69 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Post-menopausal women at high risk for development of breast cancer
  • On a stable dose of hormone replacement therapy
  • have cytomorphologic evidence of hyperplasia +/- atypia and Ki-67 expression >1.5% in benign breast epithelial cells acquired by RPFNA
  • Serum level of 25-OH vitamin D of at least 30 ng/ml prior to study entry
  • Willing to have a repeat random periareolar fine needle aspiration (RPFNA) and mammogram at 6 months and 12 months (if participating in the open label portion of the study) following initiation of study drug

Exclusion Criteria:

  • Prior history of osteoporosis or osteoporotic fracture.
  • Prior history of invasive breast cancer or other invasive cancer within five years from date of study entry.
  • Current and chronic use of cyclooxygenase-2 (COX-2) specific inhibitors or NSAIDs
  • Receiving treatment for rheumatoid arthritis or fibromyalgia
  • Current history of poorly controlled migraines or perimenopausal symptoms
  • Currently receiving other investigational agents.
  • Receipt of more than 6 months of an aromatase inhibitor (anastrozole, exemestane, letrozole, etc.) at any time in the past.

Sites / Locations

  • University of Kansas Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Letrozole

Placebo

Arm Description

Letrozole, 2.5 mg daily for 6 months

Placebo, daily for 6 months

Outcomes

Primary Outcome Measures

Change in Proliferation Rate (Ki-67 by Immunocytochemistry) From Baseline to 6 Months
Change in proliferation rate (percent positively stained cells for Ki-67 antigen by immunocytochemistry) in benign breast epithelial cells acquired by random periareolar fine needle aspiration (RPFNA) from women at high risk for the development of breast cancer.

Secondary Outcome Measures

Assessment of Change in Morphology by the Masood Score.
Masood score is a semi-quantitative index of increasing abnormality, thus higher values are worse. Range 6 to 24. Based on Masood S, Frykberg ER, McLellan GL, Scalapino MC, Mitchum DG, Bullard JB. Prospective evaluation of radiologically directed fine-needle aspiration biopsy of nonpalpable breast lesions. Cancer 1990; 66:1480-7.
Change in Mammographic Density From Baseline to 6 Months..
Percent area of the breast considered to be at increased density, as determined by the computer program Cumulus..

Full Information

First Posted
December 18, 2007
Last Updated
May 18, 2023
Sponsor
Carol Fabian, MD
Collaborators
Novartis, National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00579826
Brief Title
Study of Breast Cancer Prevention by Letrozole in High Risk Women
Official Title
Study of Breast Cancer Prevention by Letrozole in High Risk Women
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
October 2006 (undefined)
Primary Completion Date
March 2015 (Actual)
Study Completion Date
August 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Carol Fabian, MD
Collaborators
Novartis, National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a multi-institution double-blind placebo-controlled trial whose main objective is to determine if 6 months of letrozole (2.5 mg daily) can reduce proliferation as assessed by Ki-67 in high risk postmenopausal women on systemic hormone replacement therapy who have random periareolar fine needle aspiration (RPFNA) evidence of hyperplasia with atypia or borderline atypia, and a minimum Ki-67 of >1.5%. The primary hypothesis is that proliferation and expression of other estrogen response genes will be favorably modulated by six months of letrozole relative to placebo without substantially increasing hot flashes or worsening overall quality of life.
Detailed Description
Subsequent to the 6 month RPFNA for assessment of biomarkers, toxicity and quality of life assessments, all women may receive optional open-label letrozole for an additional 6 months, followed by a third RPFNA and biomarker

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
55 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Letrozole
Arm Type
Experimental
Arm Description
Letrozole, 2.5 mg daily for 6 months
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo, daily for 6 months
Intervention Type
Drug
Intervention Name(s)
Letrozole
Other Intervention Name(s)
Letrozole(Femara)
Intervention Description
Letrozole 2.5 mg tablet daily. Then optional open label letrozole for another 6 months.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo tablet daily for 6 months then optional open label letrozole for 6 months.
Primary Outcome Measure Information:
Title
Change in Proliferation Rate (Ki-67 by Immunocytochemistry) From Baseline to 6 Months
Description
Change in proliferation rate (percent positively stained cells for Ki-67 antigen by immunocytochemistry) in benign breast epithelial cells acquired by random periareolar fine needle aspiration (RPFNA) from women at high risk for the development of breast cancer.
Time Frame
Baseline to 6 Months
Secondary Outcome Measure Information:
Title
Assessment of Change in Morphology by the Masood Score.
Description
Masood score is a semi-quantitative index of increasing abnormality, thus higher values are worse. Range 6 to 24. Based on Masood S, Frykberg ER, McLellan GL, Scalapino MC, Mitchum DG, Bullard JB. Prospective evaluation of radiologically directed fine-needle aspiration biopsy of nonpalpable breast lesions. Cancer 1990; 66:1480-7.
Time Frame
Baseline to 6 Months
Title
Change in Mammographic Density From Baseline to 6 Months..
Description
Percent area of the breast considered to be at increased density, as determined by the computer program Cumulus..
Time Frame
Baseline to 6 Months
Other Pre-specified Outcome Measures:
Title
Change in Fibromyalgia Impact Questionnaire (FIQ) Score.
Description
Assessment of impact of fibromyalgia on everyday living activities. Composite score ranges from 0 (best, no interference or impact on activities) to 104 (worst, maximum interference with activities).
Time Frame
Baseline to 6 months
Title
Change in Brief Fatigue Inventory (BFI) Score.
Description
Assessment of the extent to which fatigue interferes in normal everyday living activities. Change over 6 months of treatment is assessed. Range from 0 (best, no fatigue) to 10 (worst). Increase in score indicates greater intensity of fatigue and/or greater interference with activities due to fatigue.
Time Frame
baseline to 6 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Post-menopausal women at high risk for development of breast cancer stable dose of hormone replacement therapy have cytomorphologic evidence of hyperplasia +/- atypia and Ki-67 expression >1.5% in benign breast epithelial cells acquired by RPFNA Serum level of 25-hydroxyvitamin D of at least 30 ng/ml prior to study entry Willing to have a repeat random periareolar fine needle aspiration (RPFNA) and mammogram at 6 months and 12 months (if participating in the open label portion of the study) following initiation of study drug Exclusion Criteria: Prior history of osteoporosis or osteoporotic fracture. Prior history of invasive breast cancer or other invasive cancer within five years from date of study entry. Current and chronic use of cyclooxygenase-2 (COX-2) specific inhibitors or NSAIDs Receiving treatment for rheumatoid arthritis or fibromyalgia Current history of poorly controlled migraines or perimenopausal symptoms Currently receiving other investigational agents. Receipt of more than 6 months of an aromatase inhibitor (anastrozole, exemestane, letrozole, etc.) at any time in the past.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carol J Fabian, MD
Organizational Affiliation
University of Kansas Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Global results will be published.

Learn more about this trial

Study of Breast Cancer Prevention by Letrozole in High Risk Women

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