Clinical Trials /

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

NCT02010021

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Presurgical Treatment With Letrozole in Patients With Early-stage Breast Cancer.
  • Official Title: Presurgical Treatment With Letrozole in Patients With Early-stage Breast Cancer.

Clinical Trial IDs

  • ORG STUDY ID: D13236
  • NCT ID: NCT02010021

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
LetrozoleFemaraLetrozole-presurgical

Purpose

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 RAD001 (Everolimus) 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.

Trial Arms

NameTypeDescriptionInterventions
No drug treatmentNo InterventionPost-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.
    Letrozole-presurgicalActive ComparatorPatients 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.
    • Letrozole

    Eligibility Criteria

            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 HER2 (human epidermal growth factor receptor 2) negative
                 (IHC 0-1+, or with a 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).
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:Female
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:IRS-1/PI3K/AKT pathway activation
    Time Frame:1 year
    Safety Issue:
    Description:The primary endpoint of this trial is the level of IRS/PI3K (Phosphatidylinositide 3-kinase)/AKT (protein kinase B) pathway activation in primary tumors, measured by densitometric analysis of immunoblot signals of markers of pathway activation (IRS-1, phospho-IRS-1-Ser636/639, phospho-AKT-T308, phospho-AKT-S473).

    Secondary Outcome Measures

    Measure:Ki67 score
    Time Frame:1 year
    Safety Issue:
    Description:The secondary endpoint is Ki67 score, as determined by the percentage of Ki67+ tumor cells by immunohistochemistry.

    Details

    Phase:N/A
    Primary Purpose:Interventional
    Overall Status:Active, not recruiting
    Lead Sponsor:Dartmouth-Hitchcock Medical Center

    Trial Keywords

    • breast cancer
    • postmenopausal
    • letrozole
    • RAD001
    • Everolimus

    Last Updated

    July 3, 2017