Presurgical Treatment With Letrozole in Patients With Early-stage Breast Cancer.

January 9, 2019 updated by: Gary Schwartz, Dartmouth-Hitchcock Medical Center

Some tumors use estrogen in the body to assist with growth. Letrozole is a drug that is prevents cells from producing estrogens. This should assist with the slowing of growth of tumor cells. Letrozole also promotes cell destruction by inhibiting a cellular destruction pathway.

The objectives of this study will look at the differences between the cellular destruction pathway before and after letrozole use, and the differences in the cellular destruction pathway in participants that have received letrozole versus those who did not. The study will also look at a gene in all participants called Ki67. This gene is associated with the rate of tumor cell growth. The study will measure the levels of Ki67 and compare them to the amount of activation of the cellular destruction pathway.

Participants in this study will have undergone a diagnostic biopsy of their breast tissue.

In order to meet these objectives, one group of participants (Arm A) will not receive letrozole. Tissue leftover from their diagnostic biopsy will be treated with everolimus (RAD001) in the laboratory and the effects of this drug on the cellular destruction pathway will be studied.

The other group of participants (Arm B) will take letrozole for a minimum of 10 and maximum of 21 days. They will have a second tumor sample taken as part of their surgical procedure completed to remove the tumor tissue. Any differences in the cellular destruction pathway before and after exposure to letrozole will be measured.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

17

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth Hitchcock Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Histologic Documentation of invasive breast cancer by core needle or incisional biopsy. Excess baseline biopsy tumor tissue sufficient to make three 5-micron sections must be available for molecular analyses as part of this study.
  • The invasive cancer must be estrogen receptor alpha (ER)-positive, with ER staining present in greater than 50% staining of invasive cancer cells by IHC.
  • The invasive cancer must be human epidermal growth factor receptor 2 (HER2) negative (IHC 0-1+, or with a fluorescence in situ hybridization (FISH) ratio of <1.8 if IHC is 2+ or if IHC has not been done).
  • Clinical stage I-III invasive breast cancer with the intent to treat with surgical resection of the primary tumor. Tumor must be ≥ 2cm to provide adequate tissue.
  • Patients with multi-centric or bilateral disease are eligible if the target lesions meet the other eligibility criteria. Samples from all available tumors are requested for research purposes.
  • Women ≥ age 18, for whom adjuvant treatment with an aromatase inhibitor would be clinically indicated. Women must be either post-menopausal, or pre-menopausal having undergone oophorectomy.
  • Patients must meet the following clinical laboratory criteria:

Absolute neutrophil count (ANC)≥ 1000/mm3 and platelet count ≥ 75,000/mm3. Total bilirubin ≤ 1.5 X the upper limit of normal range (ULN). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN.

- Ability to give informed consent.

Exclusion Criteria:

  • Prior endocrine therapy for any histologically confirmed cancer is not allowed. Prior endocrine therapy that was administered ≥ 5 years ago for the prevention of breast cancer in patients with no history of breast cancer is allowed.
  • Systemic drug treatment to induce ovarian suppression if woman is pre-menopausal.
  • Any other neoadjuvant therapy for breast cancer (i.e., treatment with any other anti-cancer agent besides Letrozole (10-21)days before surgical resection of the primary tumor).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: No drug treatment
Post-menopausal women with stage I-III breast cancer will have surgical resection of tumor and tumor tissue will be used to study cell growth signaling pathways ex-vivo.
Active Comparator: Letrozole-presurgical
Patients will receive Letrozole for 10-21 days prior to surgical resection of tumor tissue. This tissue will be used ex-vivo to study cell growth signaling pathway. The results will be compared to arm of the study with no intervention.
Drug: Letrozole
Patients will receive Letrozole for 10-21 days prior to surgical resection of tumor tissue. This tissue will be used ex-vivo to study cell growth signaling pathway. The results will be compared to arm of the study with no intervention.
Other Names:
  • Femara

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Insulin Receptor Substrate 1 (IRS-1) / Phosphoinositide 3-kinase (PI3K) / Serine-threonine Protein Kinase (AKT) Pathway Activation
Time Frame: baseline and surgery, approximately 30 days
The Primary Endpoint is to determine the effect of ex vivo mTORC1 inhibition with everolimus (RAD001) on IRS-1/PI3K/AKT pathway activation (as measured by phospho-AKT-T308 and phospho-AKT-S473) in ER+/human epidermal growth factor receptor 2 (HER2)- breast tumors treated with presurgical letrozole compared to ER+/HER2- breast tumors not treated with presurgical therapy.
baseline and surgery, approximately 30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Ki67 Score
Time Frame: baseline and surgery, approximately 30 days

The Secondary Endpoint is to compare tumor cell proliferation as measured with the Ki-67 assay in breast cancer specimens taken before and at the time of surgery, comparing specimens of patients treated with presurgical letrozole and specimens of patients who did not receive presurgical letrozole. The secondary endpoint is Ki67 score, as determined by the percentage of Ki67+ tumor cells identified by immunohistochemistry.

Whole slides were scanned at 40x (Aperio AT2, Leica Biosystems), and automated Ki67 analysis (percent positive nuclei) was determined using the Aperio ImageScope (v12.3.1.60002, Leica Biosystems) nuclear v9 algorithm. As recommended by the International Ki67 in Breast Cancer Working Group, 3 high-power microscopic fields were selected for analysis to represent the spectrum of staining present on the whole tissue section, and a minimum of 500 malignant invasive cells were score
baseline and surgery, approximately 30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dartmouth-Hitchcock Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2014

Primary Completion (Actual)

December 8, 2017

Study Completion (Actual)

December 8, 2017

Study Registration Dates

First Submitted

November 22, 2013

First Submitted That Met QC Criteria

December 9, 2013

First Posted (Estimate)

December 12, 2013

Study Record Updates

Last Update Posted (Actual)

January 17, 2019

Last Update Submitted That Met QC Criteria

January 9, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D13236

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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