Acolbifene in Preventing Cancer in Premenopausal Women at High Risk of Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      This phase II trial is studying how well acolbifene works in preventing cancer in
      premenopausal women at high risk of breast cancer. Chemoprevention is the use of certain
      drugs to keep cancer from forming. The use of acolbifene may stop cancer from growing or
      coming back.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      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%..

      SECONDARY OBJECTIVES:

      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
      fasting IGF-1/IGFBP-3.

      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
      N-telopeptide crosslinks).

      V. To assess any increase in reported hot flashes, menstrual cycle irregularities, pelvic
      pain, musculoskeletal complaints, and fatigue from baseline.

      OUTLINE:

      Patients receive oral acolbifene hydrochloride once daily for 6 months in the absence of
      unacceptable toxicity.

      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 antithrombin III.

      After completion of study treatment, patients are followed at 2 weeks.
    

Intervention name(s): acolbifene hydrochloride
Intervention type(s): Drug
Intervention description(s): Given orally
Other intervention name(s): EM-652.HCL; SCH 57068.HCl
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention