Clinical Trials /

GCC 1366: Anti-Proliferative Response to NeoAdjuvant AIs in Overweight and Obese Patients

NCT02095184

Description:

More than three quarter of patients with breast cancer are treated by hormone pills called tamoxifen and aromatase inhibitors (AIs). AIs are drugs that stop female hormone production. This hormone production mostly happens in fat, muscle, and breast tissue in postmenopausal women. The female hormone estrogen is an important hormone for the growth of breast cancer cells. Anastrozole (Arimidex®) and Letrozole (Femara®) are AIs that are approved by the Food and Drug Administration (FDA). They have been used since 2005 to treat women with early stage breast cancer. When given before surgery (neoadjuvant), both anastrozole and letrozole have been shown to successfully shrink breast cancer tumors in most patients. In over 50% of patients, anastrozole and letrozole when given for about 4 months also helped to improve surgery outcomes. On top of that, whether or not a patient responds to anastrozole and letrozole before surgery can help the doctor decide whether that patient needs additional chemotherapy. One of the things may influence the level of hormone is body weight. It has been previously shown that postmenopausal women with higher body fat have higher level of female hormone as well as an increased risk of breast cancer. This is likely due to an increase in aromatase activity in the fatty tissue. However, at the current time AIs are used at the same doses in all women with breast cancer no matter whether they have different body weight. Currently, we do not know for certain whether the same doses of AIs work as well in patients with higher body fat compared to patients with less body fat. The purpose of this study is to see if women with higher body fat respond differently to AI treatment compared to women with lower body fat.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

N/A

Trial Eligibility

Document

GCC 1366: Anti-Proliferative Response to NeoAdjuvant AIs in Overweight and Obese Patients

Title

  • Brief Title: GCC 1366: Anti-Proliferative Response to NeoAdjuvant AIs in Overweight and Obese Patients
  • Official Title: GCC 1366: A Prospective Study of Neoadjuvant Non-Steroidal Aromatase Inhibitors to Evaluate Anti-Proliferative Response in Obese and Overweight Patients
  • Clinical Trial IDs

    NCT ID: NCT02095184

    ORG ID: HP-00057786

    Trial Conditions

    Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Anastrozole Cohort 1: Normal Weight Anastrozole, Cohort 2: Overweight Anastrozole, Cohort 3: Obese
    Letrozole Cohort 4: Normal Weight Letrozole, Cohort 5: Overweight Letrozole, Cohort 6: Obese Letrozole

    Trial Purpose

    More than three quarter of patients with breast cancer are treated by hormone pills called
    tamoxifen and aromatase inhibitors (AIs). AIs are drugs that stop female hormone production.
    This hormone production mostly happens in fat, muscle, and breast tissue in postmenopausal
    women. The female hormone estrogen is an important hormone for the growth of breast cancer
    cells. Anastrozole (Arimidex) and Letrozole (Femara) are AIs that are approved by the Food
    and Drug Administration (FDA). They have been used since 2005 to treat women with early
    stage breast cancer.

    When given before surgery (neoadjuvant), both anastrozole and letrozole have been shown to
    successfully shrink breast cancer tumors in most patients. In over 50% of patients,
    anastrozole and letrozole when given for about 4 months also helped to improve surgery
    outcomes. On top of that, whether or not a patient responds to anastrozole and letrozole
    before surgery can help the doctor decide whether that patient needs additional
    chemotherapy.

    One of the things may influence the level of hormone is body weight. It has been previously
    shown that postmenopausal women with higher body fat have higher level of female hormone as
    well as an increased risk of breast cancer. This is likely due to an increase in aromatase
    activity in the fatty tissue. However, at the current time AIs are used at the same doses in
    all women with breast cancer no matter whether they have different body weight. Currently,
    we do not know for certain whether the same doses of AIs work as well in patients with
    higher body fat compared to patients with less body fat.

    The purpose of this study is to see if women with higher body fat respond differently to AI
    treatment compared to women with lower body fat.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Cohort 1: Normal Weight Anastrozole Active Comparator Cohort 1: Patients with BMI < 25.0 kg/m2 treated with anastrozole Anastrozole
    Cohort 2: Overweight Anastrozole Active Comparator Cohort 2: Patients with BMI 25.0-29.9 kg/m2 treated with anastrozole Anastrozole
    Cohort 3: Obese Active Comparator Cohort 3: Patients with BMI 30 kg/m2 treated with anastrozole Anastrozole
    Cohort 4: Normal Weight Letrozole Active Comparator Cohort 4: Patients with BMI < 25.0 kg/m2 treating with letrozole Letrozole
    Cohort 5: Overweight Letrozole Active Comparator Cohort 5: Patients with BMI 25.0-29.9 kg/m2 treating with letrozole Letrozole
    Cohort 6: Obese Letrozole Active Comparator Cohort 6: Patients with BMI 30 kg/m2 treating with letrozole Letrozole

    Eligibility Criteria

    Inclusion Criteria:

    1. Female greater than or equal to 18 years.

    2. Histologically confirmed or presumptive or previously defined adenocarcinoma of the
    breast.

    3. Evidence of hormone sensitivity (estrogen receptor [ER] and/or progesterone receptor
    [PR] 1%) of primary tumor tissue.

    4. Human estrogen receptor -2 (HER2) negative in the primary tumor tissue as defined
    by:

    1. Grade 0 or 1+ staining intensity (on a scale of 0 to 3) by means of IHC analysis
    OR

    2. Grade 2+ staining intensity by means of immuno-histochemical (IHC) analysis with
    gene amplification on fluorescence in situ hybridization (FISH) < 2.0 OR

    3. Gene amplification on fluorescence in situ hybridization (FISH) < 2.0.

    5. Eastern Cooperative Oncology Group (ECOG) performance status 3

    6. Unresected operable presumptive or previously defined breast cancer stage I-III with
    primary tumor 1.0 cm.

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

    8. Patients must not have received any prior chemotherapy, radiation therapy, or
    endocrine therapy for their current breast cancer. Patients who received tamoxifen or
    raloxifene or another agent for prevention of breast cancer may be included as long
    as the patient has discontinued the treatment at least one month prior to baseline
    study biopsy.

    9. Patients must have an adequate tumor tissue sample prior to enrollment available for
    correlative studies as defined below: Core needle biopsy or incisional biopsy samples
    that can provide 5 unstained sections of 5 micron thickness. Fine needle aspiration
    (FNA) sample alone is not sufficient.

    10. Patients must have adequate organ function as defined below:

    1. Total bilirubin within normal institutional limits

    2. aspartate aminotransferase (AST)(SGOT)/alanine aminotransferase (ALT)(SGPT) <
    2.5 x institutional upper limit of normal

    3. Creatinine clearance 10 mL/min/1.73 m2

    Exclusion Criteria:

    1. Previous or current systemic malignancy within the past 3 years other than breast
    cancer or adequately treated cervical carcinoma in situ or basal/squamous carcinoma
    of the skin.

    2. Patients may not be receiving any other investigational agent.

    3. History of allergic reactions or hypersensitivity to compounds of similar chemical or
    biologic composition to anastrozole.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    Percent change in proliferative index (Ki67) after treatment with the standard dose anastrozole or letrozole in normal, obese, and overweight patients

    Secondary Outcome Measures

    Trial Keywords

    Breast Cancer

    Postmenopausal

    Hormone-Receptor Positive