Exemestane and Celecoxib in Postmenopausal Women at High Risk for Breast Cancer
Condition: Breast Neoplasms
MeSH terms: Breast Neoplasms
Intervention: Exemestane; Calcium carbonate; Vitamin D
Intervention description: exemestane 25 mg by mouth (PO) every day for two years; calcium carbonate 1200 mg PO every day x 2 years; Vitamin D 400 international units PO every day x 2 years
Intervention MeSH terms: Vitamin D; Exemestane; Calcium Carbonate; Calcium
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 46.0
Sex: Female
Healthy volunteers: No
Keywords: Chemoprevention; Mammographic Density; Bone Mineral Density; Biomarkers; Safety; Breast Cancer; Postmenopausal

Summary:

      The primary goal of this 5-year study is to determine whether exemestane alone or in
      combination with celecoxib decreases breast tissue density in healthy postmenopausal women at
      high risk for breast cancer. Dense breast tissue seen on mammography has been linked to an
      increased risk of breast cancer. The study will also examine the effects of exemestane and
      celecoxib on bone density, blood hormone levels and quality of life. Exemestane, approved by
      the Food and Drug Administration for treating postmenopausal women with breast cancer, lowers
      the amount of estrogen in the body. Celecoxib, approved for treating arthritis pain and for
      reducing the number or colon polyps in an inherited syndrome, is an anti-inflammatory drug.
      Half of the women in the study will receive exemestane alone and half will receive exemestane
      and celecoxib together.

      In December 2004, the arm using exemestane and celecoxib was closed to accrual

      Postmenopausal women who are at increased risk for developing invasive breast cancer may be
      eligible to participate. Candidates are screened with breast cancer risk assessment, medical
      history and physical examination, blood tests, review of medical records, if needed, breast
      biopsy, and dual energy x-ray absorptiometry (DEXA) scan to assess bone density. For the DEXA
      scan, the subject lies still on a table for about 30 minutes while the spine and hip are
      scanned using a small amount of radiation.

      Participants take exemestane in pill form once a day for 2 years. They also take calcium and
      vitamin D pills daily to help protect bone health. They are followed in the clinic during the
      course of the study to determine the amount of drug taken and any side effects, and for the
      following tests and procedures:

        -  Medical evaluation and blood tests at after 1 and 3 months on study drugs

        -  Medical evaluation at 6 months

        -  Breast biopsy at screening and then at 12 months

        -  dual-emission x-ray absorptiometry (DEXA) scan of the spine, mammogram and routine blood
           tests before starting study drugs and then yearly for 5 years.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Postmenopausal female.

        Postmenopausal defined as no menses for at least 12 months or bilateral oophorectomy. In
        unclear cases, (e.g. 50 year old who has had hysterectomy) chemical confirmation of
        postmenopausal status may be confirmed with follicle stimulating hormone (FSH) greater than
        35 U/L.

        Elevated risk for developing invasive breast cancer by virtue of one of the following
        criteria:

        Gail Model risk of greater than or equal to 1.7% over 5 years from study entry. (This is
        the same minimum level of risk required for a subject to be eligible for the recently
        completed NSABP-P1 tamoxifen breast cancer prevention trial).

        Lobular neoplasia.

        Atypical ductal hyperplasia.

        DCIS (ductal carcinoma in situ) that has been previously treated with mastectomy or
        lumpectomy and radiation, +/- tamoxifen.

        Deleterious mutations in BRCA1 or 2 OR A priori risk assessment of 20% chance or greater of
        carrying BRCA1/2 gene mutation. The BRCAPRO and Couch model will both be used to asses this
        risk. If a woman has a 20% risk of carrying a BRCA1/2 mutation by either model, she will
        meet eligibility criteria.

        Prior stage I or II breast cancer at least 2 years out from treatment for invasive disease
        and no prior use of aromatase inhibitors.

        Subjects should be willing to abstain from use of hormonal therapies (e.g. tamoxifen,
        hormone replacement therapy, oral contraceptive pills, hormone-containing intrauterine
        devices (IUDs). E-string is acceptable). Venlafaxine will be offered as supportive care for
        women with menopausal symptoms.

        Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

        Subject has been counseled regarding her options and has signed the informed consent
        document.

        Baseline dual-emission x-ray absorptiometry (DEXA) scan with bone mineral density (BMD)
        T-score greater than or equal to 2.5 at antero posterior (AP) spine.

        Hemoglobin greater than or equal to 11 g/dl.

        Creatinine less than 1.5 times the upper limits of normal.

        Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) less than 2.5 times
        upper limit of normal.

        No investigational agent for the past 30 days.

        If history of cancer (other than squamous or basal cell skin cancers), subject must have no
        evidence of disease at time of enrollment AND no history of cancer directed treatment in
        the 2 years preceding enrollment.

        EXCLUSION CRITERIA:

        Current or recent chronic use (within 3 months) of hormonal medications, e.g. oral
        contraceptive pills, hormone replacement therapy, tamoxifen, raloxifene, IUD with
        progestins or corticosteroids. (Subjects on chronic topical or inhaled steroids will be
        eligible for the study.) Current use of phenytoin, carbamazepine, rifampin due to increased
        estrogen metabolism.

        History of clotting or bleeding disorder.

        History of allergic reactions attributed to compounds of similar chemical or biologic
        composition to exemestane (e.g. anastrozole, letrozole, formestane).

        Uncontrolled intercurrent illness including, but not limited to, ongoing or active
        infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
        arrhythmia, or psychiatric illness/social situations that would limit compliance with study
        requirements.