Phase II Study of Acolbifene in Pre-Menopausal Women at High Risk for Breast Cancer
I. To determine the effect of six months of acolbifene 20 mg/day on Ki-67 in high risk
premenopausal women with baseline hyperplasia +/- atypia and Ki-67 positivity of >= 2%..
I. To determine the effect of six months of acolbifene 20 mg/day on mammographic breast
density in high risk premenopausal women.
II. To determine the effect of six months of acolbifene 20 mg/day on serum levels of
follicular phase bioavailable estradiol, and luteal phase progesterone, testosterone, and
III. To determine the effect of six months of acolbifene 20 mg/day on epithelial cell
cytomorphology and molecular markers such as ER, PgR, and pS2.
IV. To determine the effect of six months of acolbifene on markers of cardiovascular risk
(C-reactive protein, functional AntiThrombin III, and fasting lipid profile) and bone
turnover markers associated with bone mineral density gain or loss (serum osteocalcin and
V. To assess any increase in reported hot flashes, menstrual cycle irregularities, pelvic
pain, musculoskeletal complaints, and fatigue from baseline.
Patients receive oral acolbifene hydrochloride once daily for 6 months in the absence of
Patients undergo symptom assessment (hot flashes, menstrual abnormalities, pelvic pain,
muscle and joint pain, and fatigue) at baseline, 6-8 weeks, monthly for 6 months, and then
at 2 weeks after completion of study treatment.
Patients undergo random periareolar fine needle aspiration between days 1-10 of menstrual
cycle at baseline and at 6 months. Patients also undergo blood sample collection between
days 1-10 and days 20-24 of menstrual cycle at baseline and at 6 months. Samples taken
between days 1-10 of menstrual cycle are analyzed for Ki-67 expression, cytomorphology,
molecular markers (estrogen receptor, progesterone receptor, and pS2 expression), and
bioavailable estradiol levels. Samples taken between days 20-24 of menstrual cycle are
analyzed for progesterone, testosterone, IGF-1, IGFBP-3, lipid profile, bone-turnover
markers (osteocalcin and N-telopeptide crosslinks), C-reactive protein, and functional
After completion of study treatment, patients are followed at 2 weeks.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention
Reduced proliferation as measured by Ki-67 expression in breast epithelial cells obtained by random periareolar fine needle aspiration
At 6 months
University of Kansas
United States: Food and Drug Administration
|University of Kansas Medical Center||Kansas City, Kansas 66160-7353|