Clinical Trials /

Alternative Dosing of Exemestane Before Surgery in Treating Postmenopausal Patients With Stage 0-II Estrogen Positive Breast Cancer

NCT02598557

Description:

This randomized phase IIb trial studies how well alternative dosing of exemestane before surgery works in treating in postmenopausal patients with stage 0-II estrogen positive breast cancer. Chemoprevention is the use of drugs to keep breast cancer from forming or coming back. The use of exemestane may treat early stage (stage 0-II) breast cancer. Comparing the exemestane standard dose regimen versus two alternative, less frequent dose regimens may decrease undesirable symptoms and have similar efficacy in reducing serum estradiol.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Alternative Dosing of <span class="go-doc-concept go-doc-intervention">Exemestane</span> Before Surgery in Treating Postmenopausal Patients With Stage 0-II Estrogen Positive Breast Cancer

Title

  • Brief Title: Alternative Dosing of Exemestane Before Surgery in Treating Postmenopausal Patients With Stage 0-II Estrogen Positive Breast Cancer
  • Official Title: Alternative Dosing of Exemestane in Postmenopausal Women With Stage 0-II ER-Positive Breast Cancer: A Randomized Presurgical Trial
  • Clinical Trial IDs

    NCT ID: NCT02598557

    ORG ID: NCI-2015-01821

    NCI ID: NCI-2015-01821

    Trial Conditions

    Estrogen Receptor Positive

    Postmenopausal

    Stage 0 Breast Cancer

    Stage IA Breast Cancer

    Stage IB Breast Cancer

    Stage IIA Breast Cancer

    Stage IIB Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Exemestane Aromasin, FCE-24304 Arm I (exemestane), Arm II (exemestane, placebo), Arm III (exemestane, placebo)

    Trial Purpose

    This randomized phase IIb trial studies how well alternative dosing of exemestane before
    surgery works in treating in postmenopausal patients with stage 0-II estrogen positive
    breast cancer. Chemoprevention is the use of drugs to keep breast cancer from forming or
    coming back. The use of exemestane may treat early stage (stage 0-II) breast cancer.
    Comparing the exemestane standard dose regimen versus two alternative, less frequent dose
    regimens may decrease undesirable symptoms and be more effective in treating breast cancer.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. Non-inferiority of percent change in time of serum estradiol levels, adjusted for
    baseline levels, following four up to six weeks of exemestane 25 mg given three times per
    week or one time per week compared with exemestane 25 mg daily dosing.

    SECONDARY OBJECTIVES:

    I. To assess safety and toxicity. II. To support the preventive activity of exemestane we
    will investigate the change in Ki67 and progesterone receptor (PgR) levels in tumor cells
    and the adjacent intraepithelial neoplasia or benign histologic structures.

    III. To assess possible association of estradiol level with tissue and circulating
    biomarkers.

    IV. To investigate possible pharmacogenetic markers. V. To assess drug levels on tissue
    samples. VI. To investigate tissue and circulating proteomics profiling.

    OUTLINE: Patients are randomized to 1 of 3 treatment arms.

    ARM I: Patients receive exemestane orally (PO) once daily (QD) on days 1-7.

    ARM II: Patients receive exemestane PO QD on days 1, 3, and 5. Patients also receive placebo
    PO QD on days 2, 4, 6, and 7.

    ARM III: Patients receive exemestane PO QD on day 1 and placebo PO QD on days 2-7.

    In all arms, courses repeat every 7 days for 4-6 weeks in the absence of disease progression
    or unacceptable toxicity. Patients then undergo surgery between days 29-43.

    Trial Arms

    Name Type Description Interventions
    Arm I (exemestane) Experimental Patients receive exemestane PO QD on days 1-7. Courses repeat every 7 days for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Exemestane
    Arm II (exemestane, placebo) Experimental Patients receive exemestane PO QD on days 1, 3, and 5. Patients also receive placebo PO QD on days 2, 4, 6, and 7. Courses repeat every 7 days for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Exemestane
    Arm III (exemestane, placebo) Experimental Patients receive exemestane PO QD on day 1 and placebo PO QD on days 2-7. Courses repeat every 7 days for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Exemestane

    Eligibility Criteria

    Inclusion Criteria:

    - Postmenopausal women (* postmenopausal: age >= 60 years, or amenorrhea >= 12 months,
    or bilateral oophorectomy, or in women with hysterectomy only follicle stimulating
    hormone [FSH] > 30 IU/L if < 60 years old) with histologically confirmed estrogen
    receptor (ER) positive (>= 10%) primary breast cancer stage T02, N01, Mx; women with
    larger tumors who refuse chemotherapy (chemo) and/or endocrine neoadjuvant therapy
    can be eligible

    - Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)

    - Leukocytes >= 3,000/microliter

    - Absolute neutrophil count >= 1,500/microliter

    - Platelets >= 100,000/microliter

    - Total bilirubin =< 2 x institutional upper limit of normal (ULN)

    - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
    [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
    =< 1.5 institutional ULN

    - Creatinine within normal institutional limits

    - Ability to understand and the willingness to sign a written informed consent document

    Exclusion Criteria:

    - Body mass index (BMI) < 18.5 Kg/m^2

    - Previous treatment for breast cancer including chemotherapy and endocrine therapy

    - Women who are planned to receive neoadjuvant therapy

    - Participants may not be receiving investigational agents

    - History of allergic reactions attributed to compounds of similar chemical or biologic
    composition to exemestane

    - 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

    - Other coexisting malignancies (with the exclusion of basal cell carcinoma or skin
    squamous cell carcinoma) diagnosed during the last 2 years before randomization

    - History of severe osteoporosis (T score =< -4 either spine or hip), or presence of
    vertebral fracture

    - Use of hormone replacement therapy (HRT) in the last 30 days prior to the
    randomization

    - Use of any chemopreventive agents (selective estrogen receptor modulators [SERM]) in
    the last 3 months

    - Concomitant use of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)
    inducer medication (rifampicin, phenytoin, carbamazepine, phenobarbital, and St.
    John's wort)

    Minimum Eligible Age: N/A

    Maximum Eligible Age: 75 Years

    Eligible Gender: Female

    Primary Outcome Measures

    Percentage change of serum estradiol concentration

    Secondary Outcome Measures

    Additional validated method of estradiol measurement

    Androstenedione and testosterone expression measured by radioimmunoassay

    Breast tissue estradiol concentration in tumor and breast fat

    Change in Ki67 expression

    Change in leptin and adiponectin serum concentrations measured by enzyme linked immunoassays

    Change in serum drug measurements of exemestane and 17-dihydroxyexemestane at the end of treatment

    Changes in estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression levels

    Changes in the occurrence of crown like structures in mammary fat tissue by immunohistochemistry

    Incidence of toxicity graded according to the Common Terminology Criteria for Adverse Events version 4.0 and Menopause-Specific Quality of Life Questionnaire

    Insulin and glucose concentrations measured with the Architect Immunoassay analyzer

    Ki67 in adjacent intraepithelial neoplasia and or grossly benign tissue

    Proteomic analysis

    Serum concentrations of estrone and estrone sulfate measured by liquid chromatography coupled with tandem mass spectrometry

    Sex hormone binding globulin serum levels measured by a chemiluminescent microparticle immunoassay

    UDP glucuronosyltransferase 2 family, polypeptide B17 gene analysis assessed by the Taqman copy number variation assay

    Trial Keywords