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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2016 by University of Maryland
Sponsor:
Information provided by (Responsible Party):
Susan Kesmodel, University of Maryland
ClinicalTrials.gov Identifier:
NCT02095184
First received: March 20, 2014
Last updated: May 10, 2016
Last verified: May 2016

March 20, 2014
May 10, 2016
May 2015
March 2018   (final data collection date for primary outcome measure)
Percent change in proliferative index (Ki67) after treatment with the standard dose anastrozole or letrozole in normal, obese, and overweight patients [ Time Frame: 2-4 weeks ] [ Designated as safety issue: No ]
Percent change in proliferative index (Ki67) after treatment with the standard dose anastrozole or letrozole in normal, obese, and overweight patients
Same as current
Complete list of historical versions of study NCT02095184 on ClinicalTrials.gov Archive Site
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GCC 1366: Anti-Proliferative Response to NeoAdjuvant AIs in Overweight and Obese Patients
GCC 1366: A Prospective Study of Neoadjuvant Non-Steroidal Aromatase Inhibitors to Evaluate Anti-Proliferative Response in Obese and Overweight Patients

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.

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Interventional
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Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Breast Cancer
  • Drug: Anastrozole
    1 mg daily
  • Drug: Letrozole
    2.5 mg daily
  • Active Comparator: Cohort 1: Normal Weight Anastrozole
    Cohort 1: Patients with BMI < 25.0 kg/m2 treated with anastrozole
    Intervention: Drug: Anastrozole
  • Active Comparator: Cohort 2: Overweight Anastrozole
    Cohort 2: Patients with BMI ≥ 25.0-29.9 kg/m2 treated with anastrozole
    Intervention: Drug: Anastrozole
  • Active Comparator: Cohort 3: Obese
    Cohort 3: Patients with BMI ≥ 30 kg/m2 treated with anastrozole
    Intervention: Drug: Anastrozole
  • Active Comparator: Cohort 4: Normal Weight Letrozole
    Cohort 4: Patients with BMI < 25.0 kg/m2 treating with letrozole
    Intervention: Drug: Letrozole
  • Active Comparator: Cohort 5: Overweight Letrozole
    Cohort 5: Patients with BMI ≥ 25.0-29.9 kg/m2 treating with letrozole
    Intervention: Drug: Letrozole
  • Active Comparator: Cohort 6: Obese Letrozole
    Cohort 6: Patients with BMI ≥ 30 kg/m2 treating with letrozole
    Intervention: Drug: Letrozole
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
90
March 2019
March 2018   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Female greater than or equal to 18 years.
  2. Postmenopausal status, defined by no menstrual cycle for 12 months or surgical removal of ovaries.
  3. Histologically confirmed adenocarcinoma of the breast.
  4. Evidence of hormone sensitive, ER rich primary tumor defined by an Allred score of ≥6.
  5. 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.
  6. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3
  7. Unresected operable breast cancer stage I-III with primary tumor ≥ 2.0 cm.
  8. Ability to understand and the willingness to sign a written informed consent document.
  9. 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.
  10. 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.
  11. 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 or letrozole.
Female
18 Years and older   (Adult, Senior)
No
United States
 
NCT02095184
HP-00057786
Yes
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Susan Kesmodel, University of Maryland
University of Maryland
Not Provided
Principal Investigator: Susan Kesmodel, M.D. University of Maryland
University of Maryland
May 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP