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

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

  • ORG STUDY ID: VICC BRE 0776
  • SECONDARY ID: P50CA098131
  • SECONDARY ID: P30CA068485
  • SECONDARY ID: VU-VICC-BRE-0776
  • SECONDARY ID: VU-VICC-IRB-080064
  • NCT ID: NCT00651976

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
letrozoletreatment

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

NameTypeDescriptionInterventions
treatmentExperimental
  • 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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Ki67 index measured in hormone receptor-positive breast cancers compared to those that are hormone receptor-negative
Time Frame:day 7 to day 21
Safety Issue:
Description:Ki67 index is measured by counting the percentage of cells staining for Ki67 in a section of breast tissue. The number of stained cells will be compared in tissue that is hormone receptor-positive tissue to tissue that is hormone receptor negative.

Secondary Outcome Measures

Measure:In situ apoptotic effect of letrozole
Time Frame:day 7 to day 21
Safety Issue:
Description:Measured by level of capase-3 in post-treatment breast tissue.
Measure:Identification of a recurrence risk biomarker profile using RNA microarray
Time Frame:day 7 to day 21
Safety Issue:
Description:RNA will be extracted from pre- and post-treatment breast tissue and will be compared with the Ki67 index

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:Vanderbilt-Ingram Cancer Center

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

Last Updated

October 15, 2018