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

NCT02095184 | Terminated Results DMC

• 1 other identifier: HP-00060250
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Breast Cancer

Keywords

Breast Cancer; Postmenopausal; Hormone-Receptor Positive

Outcome Measures

Primary Outcomes (1)

• Percent Change in Proliferative Index (Ki67) After Treatment With the Standard Dose Anastrozole or Letrozole in Normal, Obese, and Overweight Patients

  Core biopsy

  2-4 weeks Post-treatment

Secondary Outcomes (9)

• To Evaluate Differences in Baseline GP88 Level

  B,0-Prior to starting anastrozole or letrozole

• To Evaluate Differences in Baseline GP88 Level

  B,1-On the day of surgery or within 3 days of surgery

• To Evaluate Differences in Baseline GP88 Level

  B,2-obtained 2-4 weeks after initiation of AI therapy( for persons rec. extended neoadjuvant tx)

• To Assess Estradiol Levels at Baseline and After Treatment (in Primary ER Positive Breast Tumors)

  Baseline

• To Assess Estradiol Levels at Baseline and After Treatment (in Primary ER Positive Breast Tumors)

  2-4 weeks Post treatment

Other Outcomes (3)

• Metabolomic Profiling

  B-0

• Metabolomic Profiling

  B-1

• Metabolomic Profiling

  B-2

Study Arms (6)

Cohort 1: Normal Weight Anastrozole

ACTIVE COMPARATOR

Cohort 1: Patients with BMI \< 25.0 kg/m2 treated with anastrozole

Drug: Anastrozole

Cohort 2: Overweight Anastrozole

ACTIVE COMPARATOR

Cohort 2: Patients with BMI ≥ 25.0-29.9 kg/m2 treated with anastrozole

Drug: Anastrozole

Cohort 3: Obese

ACTIVE COMPARATOR

Cohort 3: Patients with BMI ≥ 30 kg/m2 treated with anastrozole

Drug: Anastrozole

Cohort 4: Normal Weight Letrozole

ACTIVE COMPARATOR

Cohort 4: Patients with BMI \< 25.0 kg/m2 treating with letrozole

Drug: Letrozole

Cohort 5: Overweight Letrozole

ACTIVE COMPARATOR

Cohort 5: Patients with BMI ≥ 25.0-29.9 kg/m2 treating with letrozole

Drug: Letrozole

Cohort 6: Obese Letrozole

ACTIVE COMPARATOR

Cohort 6: Patients with BMI ≥ 30 kg/m2 treating with letrozole

Drug: Letrozole

Interventions

Anastrozole DRUG

1 mg daily

Also known as: Arimidex

Cohort 1: Normal Weight Anastrozole; Cohort 2: Overweight Anastrozole; Cohort 3: Obese

Letrozole DRUG

2.5 mg daily

Also known as: Femara

Cohort 4: Normal Weight Letrozole; Cohort 5: Overweight Letrozole; Cohort 6: Obese Letrozole

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female greater than or equal to 18 years.
• Postmenopausal status, defined by no menstrual cycle for 12 months or surgical removal of ovaries.
• Histologically confirmed adenocarcinoma of the breast.
• Evidence of hormone sensitive, ER rich primary tumor defined by an Allred score of ≥6.
• Human estrogen receptor -2 (HER2) negative in the primary tumor tissue as defined by:
• Grade 0 or 1+ staining intensity (on a scale of 0 to 3) by means of IHC analysis OR
• Grade 2+ staining intensity by means of immuno-histochemical (IHC) analysis with gene amplification on fluorescence in situ hybridization (FISH) \< 2.0 OR
• Gene amplification on fluorescence in situ hybridization (FISH) \< 2.0.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3
• Unresected operable breast cancer stage I-III with primary tumor ≥ 2.0 cm.
• Ability to understand and the willingness to sign a written informed consent document.
• 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.
• 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.
• Patients must have adequate organ function as defined below:
• Total bilirubin within normal institutional limits

You may not qualify if:

• 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.
• Patients may not be receiving any other investigational agent.
• History of allergic reactions or hypersensitivity to compounds of similar chemical or biologic composition to anastrozole or letrozole.

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (1)

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Anastrozole; Letrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Suliat Nurudeen, MD
• Organization: University of Maryland Greenebaum Comprehensive Cancer Center

SNurudeen@som.umaryland.edu

410-328-7320

Study Officials

• Emily C Bellavance, M.D.

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2014
• First Posted: March 24, 2014
• Study Start: May 25, 2015
• Primary Completion: July 24, 2024
• Study Completion: August 2, 2024
• Last Updated: April 15, 2026
• Results First Posted: April 15, 2026

Record last verified: 2026-03

Locations

US (1)