Clinical Trials /

Letrozole in Treating Postmenopausal Women With Stage I, II or III Breast Cancer That Can Be Removed by Surgery

NCT00651976

Description:

RATIONALE: Hormone therapy using letrozole may fight breast cancer by lowering the amount of estrogen the body makes. Giving letrozole before surgery allows us to monitor the effects of letrozole on the tumor on a molecular level and determine markers of response to treatment. PURPOSE: This study will show us how well letrozole works in treating postmenopausal women with stage I, II or III breast cancer that can be removed by surgery.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Terminated

Phase:

Early Phase 1

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Letrozole</span> in Treating Postmenopausal Women With Stage I, II or III <span class="go-doc-concept go-doc-disease">Breast Cancer</span> That Can Be Removed by Surgery

Title

  • Brief Title: Letrozole in Treating Postmenopausal Women With Stage I, II or III Breast Cancer That Can Be Removed by Surgery
  • Official Title: Pre-Surgical Trial of Letrozole in Post-Menopausal Patients With Operable Hormone-Sensitive Breast Cancer (Spore)
  • Clinical Trial IDs

    NCT ID: NCT00651976

    ORG ID: VICC BRE 0776

    NCI ID: P50CA098131

    Trial Conditions

    Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    letrozole treatment

    Trial Purpose

    RATIONALE: Hormone therapy using letrozole may fight breast cancer by lowering the amount of
    estrogen the body makes. Giving letrozole before surgery allows us to monitor the effects of
    letrozole on the tumor on a molecular level and determine markers of response to treatment.

    PURPOSE: This study will show us how well letrozole works in treating postmenopausal women
    with stage I, II or III breast cancer that can be removed by surgery.

    Detailed Description

    OBJECTIVES:

    Primary To determine that in breast tumors that continue to exhibit high proliferation
    (i.e., Ki67) upon hormone deprivation (with letrozole), their gene expression and/or a
    mutational or proteomic signatures will harbor molecules or 'pathways' that are biomarkers
    of resistance to endocrine therapy or a cause of it.

    The ultimate goal of these aims is to identify clinically-targetable pathways which can be
    exploited to enhance responses and survival in patients with ER+ breast cancer.

    OUTLINE: Patients receive oral letrozole once daily for 7-21 days in the absence of disease
    progression or unacceptable toxicity. Within 24 hours after the last dose of letrozole,
    patients undergo total mastectomy or segmental resection with lymph node evaluation.

    Pre-treatment diagnostic breast tissue is obtained. Patients undergo treatment and then
    undergo standard of care mastectomy or lumpectomy. Pre and post treatment tumor tissue
    samples are analyzed for Ki67, P-ER, ER, progesterone receptor (PR), and caspase 3 by
    immunohistochemistry; and RNA microarray.

    Trial Arms

    Name Type Description Interventions
    treatment Experimental letrozole

    Eligibility Criteria

    DISEASE CHARACTERISTICS:

    - Diagnosis of invasive breast cancer

    - Clinical stage I, II, or III disease

    - Resectable disease

    - Measurable disease, defined as a mass that can be reproducibly measured by physical
    examination and/or ultrasound and is at least 1 cm in size by ultrasound

    - Patients with measurable residual tumor at the primary site allowed

    - Estrogen receptor-positive tumor by immunohistochemistry (IHC)

    - HER2-negative tumor by Herceptest (0 or +1) OR HER2 not overexpressed by fluorescence
    in situ hybridization (FISH)

    - Planning to undergo surgical treatment with either segmental resection or total
    mastectomy with or without lymph node evaluation

    - Must have core biopsies from the time of diagnosis available (may include sections of
    paraffin-embedded material)

    - Prior contralateral breast cancer allowed provided there is no evidence of recurrence
    of the initial primary breast cancer

    - Patients with locally advanced disease who are candidates for preoperative
    chemotherapy at the time of initial evaluation are not eligible

    - Locally advanced disease is defined by any of the following:

    - Primary tumor 5 cm (T3)

    - Tumor of any size with direct extension to the chest wall or skin (T4a-c)

    - Inflammatory breast cancer (T4d)

    - Fixed axillary lymph node metastases (N2)

    - Metastasis to ipsilateral internal mammary node (N3)

    - No locally recurrent disease

    - No evidence of distant metastatic disease (i.e., lung, liver, bone, or brain
    metastases)

    PATIENT CHARACTERISTICS:

    - ECOG performance status 0-1

    - Postmenopausal, as defined by any of the following:

    - 55 years of age and over

    - Under 55 years of age and meets 1 of the following criteria:

    - Amenorrheic for at least 12 months

    - Follicle-stimulating hormone (FSH) 40 IU/L and estradiol levels 20 IU/L

    - Has undergone prior bilateral oophorectomy or radiation castration AND has been
    amenorrheic for at least 6 months

    - Bilirubin 1.5 times upper limit of normal (ULN)

    - SGOT and SGPT 1.5 times ULN

    - Creatinine 1.5 t times ULN

    - Able to swallow and retain oral medication

    - No serious medical illness that, in the judgment of the treating physician, places
    the patient at high risk for operative mortality

    - No malabsorption syndrome, ulcerative colitis, or other disease significantly
    affecting gastrointestinal function

    - No other malignancy within the past 5 years except for completely resected
    nonmelanoma skin cancer or successfully treated in situ carcinoma

    - No dementia, altered mental status, or any psychiatric condition that would preclude
    the understanding or rendering of informed consent

    - No severe uncontrolled malabsorption condition or disease (i.e., grade II/III
    diarrhea, severe malnutrition, or short gut syndrome)

    PRIOR CONCURRENT THERAPY:

    - See Disease Characteristics

    - At least 21 days since prior tamoxifen or raloxifene as a preventive agent

    - At least 7 days since prior hormone replacement therapy (e.g., conjugated estrogens
    [Premarin])

    - No prior resection of the stomach or small bowel

    - More than 30 days or 5 half-lives, whichever is longer, since prior investigational
    drugs

    - No prior chemotherapy for this primary breast cancer

    - No other concurrent investigational agents

    - No other concurrent anticancer therapy (e.g., chemotherapy, radiotherapy,
    immunotherapy, hormonal therapy, or any other biologic therapy)

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    Ki67 index measured in hormone receptor-positive breast cancers compared to those that are hormone receptor-negative

    Secondary Outcome Measures

    In situ apoptotic effect of letrozole

    Identification of a recurrence risk biomarker profile using RNA microarray

    Trial Keywords

    stage IA breast cancer

    stage IB breast cancer

    stage II breast cancer

    stage III breast cancer

    HER2-negative breast cancer

    estrogen receptor-positive breast cancer