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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Vanderbilt-Ingram Cancer Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Ingrid Meszoely, MD, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier:
NCT00651976
First received: April 2, 2008
Last updated: May 5, 2014
Last verified: May 2014
  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.


Condition Intervention
Breast Cancer
Drug: letrozole
Other: Blood Collection
Procedure: biopsy/lumpectomy/mastectomy

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pre-Surgical Trial of Letrozole in Post-Menopausal Patients With Operable Hormone-Sensitive Breast Cancer (Spore)

Resource links provided by NLM:


Further study details as provided by Vanderbilt-Ingram Cancer Center:

Primary Outcome Measures:
  • Ki67 index measured in hormone receptor-positive breast cancers compared to those that are hormone receptor-negative [ Time Frame: day 7 to day 21 ] [ Designated as safety issue: No ]
    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:
  • In situ apoptotic effect of letrozole [ Time Frame: day 7 to day 21 ] [ Designated as safety issue: No ]
    Measured by level of capase-3 in post-treatment breast tissue.

  • Identification of a recurrence risk biomarker profile using RNA microarray [ Time Frame: day 7 to day 21 ] [ Designated as safety issue: No ]
    RNA will be extracted from pre- and post-treatment breast tissue and will be compared with the Ki67 index


Estimated Enrollment: 200
Study Start Date: March 2008
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: treatment Drug: letrozole
Take by mouth at a dose of 2.5 mg on days 7-21
Other: Blood Collection
Blood used for gene expression analysis and reverse transcriptase-polymerase chain reaction
Procedure: biopsy/lumpectomy/mastectomy
Tissue collection,Surgery to remove tumor, Tumor tissues used for laboratory biomarker analysis

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00651976

Contacts
Contact: VICC Clinical Trials Information Program 800-811-8480

Locations
United States, Georgia
Emory University Completed
Atlanta, Georgia, United States
United States, Oklahoma
Surgical Associates, Inc. Completed
Tulsa, Oklahoma, United States, 74136
United States, Pennsylvania
Bryn Mawr Withdrawn
Bryn Mawr, Pennsylvania, United States, 19010
Allegheny Cancer Center Completed
Pittsburgh, Pennsylvania, United States, 15212
Lankenau Hospital Withdrawn
Wynnewood, Pennsylvania, United States, 19096
United States, Tennessee
Vanderbilt-Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232-6838
Contact: Clinical Trials Office - Vanderbilt-Ingram Cancer Center    800-811-8480      
Principal Investigator: Ingrid Meszoely, MD         
Vanderbilt-Ingram Cancer Center at Franklin Recruiting
Nashville, Tennessee, United States, 37064
Contact: VICC Clinical Trials Information Program    800-811-8480      
Principal Investigator: Ingrid Meszoely, MD         
Vanderbilt-Ingram Cancer Center, One Hundred Oaks Recruiting
Nashville, Tennessee, United States, 37204
Contact: Clinical Trials Office - Vanderbilt-Ingram Cancer Center    800-811-8480      
Principal Investigator: Ingrid Meszoely, MD         
Sponsors and Collaborators
Vanderbilt-Ingram Cancer Center
Investigators
Principal Investigator: Ingrid Meszoely, MD Vanderbilt-Ingram Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Ingrid Meszoely, MD, Associate Professor of Surgery (Surgical Oncology); Clinical Director, Vanderbilt Breast Center; Surgical Oncologist, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier: NCT00651976     History of Changes
Other Study ID Numbers: VICC BRE 0776, P50CA098131, P30CA068485, VU-VICC-BRE-0776, VU-VICC-IRB-080064
Study First Received: April 2, 2008
Last Updated: May 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Vanderbilt-Ingram Cancer Center:
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

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Letrozole
Antineoplastic Agents
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014