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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

Phase 2
18 Years
Open (Enrolling)
Breast Cancer

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Trial Information

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


- 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

Inclusion Criteria


- 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

- 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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Prevention

Principal Investigator

Carol J. Fabian, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of Kansas


United States: Federal Government

Study ID:




Start Date:

August 2000

Completion Date:

Related Keywords:

  • Breast Cancer
  • breast cancer
  • Breast Neoplasms
  • Hyperplasia



University of Kansas Medical Center Kansas City, Kansas  66160-7353
U.S. Oncology Research, Inc. Dallas, Texas  75246