LY353381 in Preventing Breast Cancer in Women With Hyperplasia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00005879
Recruitment Status : Completed
First Posted : January 27, 2003
Results First Posted : May 30, 2017
Last Update Posted : May 30, 2017
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Carol Fabian, MD, University of Kansas Medical Center

Brief Summary:

RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. The use of LY353381 may be an effective way to prevent the development of breast cancer in women who have hyperplasia.

PURPOSE: Randomized phase II trial to study the effectiveness of LY353381 in preventing breast cancer in women who have hyperplasia.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: arzoxifene Drug: Placebo Phase 2

Detailed Description:


  • Determine if LY353381 hydrochloride improves baseline cytology in women at high risk for breast cancer.
  • Determine if this drug modulates other potential surrogate endpoint biomarkers or drug effect biomarkers.
  • Determine if cytologic improvement is associated with initial presentation of the various stratification factors.
  • Determine whether cytology is correlated with other potential surrogate endpoint biomarkers or drug effect biomarkers and whether change in cytology is correlated with change in the other biomarkers.
  • Monitor the effects of this drug in terms of quality of life and women's health.

OUTLINE: This is a randomized, double-blind, multicenter study followed by an open-label study for both arms. Patients are stratified according to cytologic status (hyperplasia with atypia vs hyperplasia without atypia), mutation status (known carrier for BRCA1 or BRCA2 genes vs known not to be a carrier of mutant genes), menopausal status (premenopausal vs postmenopausal), estrogen-receptor status, and participating center. Patients are randomized to one of two treatment arms.

  • Arm I: Patients receive oral LY353381 hydrochloride once daily for 6 months.
  • Arm II: Patients receive oral placebo once daily for 6 months. Patients in both arms then receive oral LY353381 hydrochloride for an additional 6 months.

Quality of life is assessed at baseline and then at 6 and 12 months.

Patients are followed at 2 weeks and then annually for 5 years.

PROJECTED ACCRUAL: A total of 210-220 patients will be accrued for this study within 2.5-3 years.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 199 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase II Clinical Trial of a Selective Estrogen Receptor Modulator (LY353381*HCl) in High Risk Women With Fine Needle Aspiration Cytologic Evidence of Hyperplasia
Study Start Date : August 2000
Actual Primary Completion Date : July 2008
Actual Study Completion Date : July 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Placebo Comparator: Placebo
Drug: Placebo
matched tablet dialy

Experimental: Arzoxifene
LY353381, 20 mg daily
Drug: arzoxifene
one tablet daily
Other Name: LY353381

Primary Outcome Measures :
  1. Change in Masood Score [ Time Frame: Baseline to 6 months ]

    Change in the semi-quantitative score assigned by the designated cytopathologist.

    Range 6-24. Score represents increasing abnormality (i.e., worse appearance) Sum composite of 6 cytomorphological features, each scored as 1-4.

  2. Number of Participants With Improvement From Baseline in Cytomorphologic Abnormality at 6 Months [ Time Frame: Baseline to 6 months ]

    Change (improvement) in categorical descriptor of cytologic abnormality as assigned by the primary cytopathologist.

    Categories include: normal (non-proliferative), epithelial hyperplasia, epithelial hyperplasia with atypia.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes


  • Current random fine needle breast aspiration (FNA) evidence of 1 of the following:

    • Hyperplasia with atypia
    • Hyperplasia without atypia but with a 10-year modified Gail risk of at least 4%
    • Hyperplasia without atypia but with a BRCAPRO risk of at least 25%
    • Hyperplasia without atypia but with a known mutation in BRCA1 or BRCA2
    • Hyperplasia without atypia but with a history of contralateral ductal carcinoma in situ or invasive breast cancer
  • FNA must have been taken during days 1-14 of the menstrual cycle for premenopausal women
  • Classified as ACR class I-III on mammogram with stepwedge within past 6 months If intact uterus and/or ovaries, must have color doppler transvaginal pelvic sonogram within past 6 months showing endometrial thickening no greater than 13 mm premenopausal or no greater than 8 mm postmenopausal

    • No ovarian cysts felt to be possibly or probably non-physiologic that have not resolved to gynecologist's satisfaction on repeat sonogram
  • Must agree to have or have had genetic counseling and genetic testing performed for BRCA1 and BRCA2
  • No active cancer (e.g., detectable disease)
  • Hormone receptor status:

    • Not specified



  • 18 and over


  • Female

Menopausal status:

  • Any

Performance status:

  • Not specified

Life expectancy:

  • At least 12 months


  • Hemoglobin greater than 10 g/dL
  • Granulocyte count greater than 1,000/mm^3
  • No deficiencies in protein C, protein S, or antithrombin III
  • No activated protein C resistance


  • Albumin greater than 3.0 g/dL
  • Bilirubin less than 1.5 mg/dL
  • AST less than 100 U/L
  • Alkaline phosphatase less than 200 U/L


  • Creatinine less than 1.5 mg/dL


  • No history of deep venous thrombosis not related to trauma or pregnancy
  • No severe coronary artery disease
  • No history of prior stroke


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after study
  • No other active cancer
  • No retinal vein thrombosis
  • No concurrent severe poorly controlled migraine
  • No factor V Leiden mutation carrier


Biologic therapy:

  • At least 12 months since prior immunotherapy


  • At least 3 months between completion of prior KUMC phase II difluoromethylornithine (DFMO) study and baseline aspiration
  • At least 12 months since prior chemotherapy

Endocrine therapy:

  • Must not have started or stopped hormone replacement therapy or oral contraceptives within 6 months of baseline aspiration
  • Must continue all hormone replacement therapy and/or oral contraceptives that were being taken at time of baseline aspiration
  • At least 12 months since prior tamoxifen, raloxifene, or other antihormonal therapy


  • At least 3 months since prior radiotherapy


  • At least 6 months between prior oophorectomy and baseline aspiration


  • At least 2 weeks since the start of other new medication that would be ingested for 1 or more months

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00005879

United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160-7820
United States, Texas
U.S. Oncology Research, Inc.
Dallas, Texas, United States, 75246
Sponsors and Collaborators
University of Kansas Medical Center
National Cancer Institute (NCI)
Study Chair: Carol J. Fabian, MD University of Kansas

Responsible Party: Carol Fabian, MD, Director, Breast Cancer Prevention Unit, University of Kansas Medical Center Identifier: NCT00005879     History of Changes
Other Study ID Numbers: KUMC-HSC-7264-97
CDR0000067918 ( Registry Identifier: PDQ (Physician Data Query) )
NCI-P00-0146 ( Other Identifier: NCI )
U01CA077165 ( U.S. NIH Grant/Contract )
First Posted: January 27, 2003    Key Record Dates
Results First Posted: May 30, 2017
Last Update Posted: May 30, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Global results will be published.

Keywords provided by Carol Fabian, MD, University of Kansas Medical Center:
breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Pathologic Processes
Estrogen Receptor Modulators
Selective Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs