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Letrozole in Treating Postmenopausal Women With Stage I or Stage II Breast Cancer That Can Be Removed by Surgery
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), October 2008
First Received: April 2, 2008   Last Updated: August 11, 2009   History of Changes
Sponsors and Collaborators: Vanderbilt-Ingram Cancer Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00651976
  Purpose

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by lowering the amount of estrogen the body makes. Giving letrozole before surgery may be an effective treatment for breast cancer.

PURPOSE: This phase I trial is studying how well letrozole works in treating postmenopausal women with stage I or stage II breast cancer that can be removed by surgery.


Condition Intervention Phase
Breast Cancer
Drug: letrozole
Genetic: RNA analysis
Genetic: gene expression analysis
Genetic: reverse transcriptase-polymerase chain reaction
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Procedure: biopsy
Procedure: neoadjuvant therapy
Procedure: therapeutic conventional surgery
Phase I

Study Type: Interventional
Study Design: Treatment, Open Label
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 National Cancer Institute (NCI):

Primary Outcome Measures:
  • Correlation of letrozole-induced reduction of Ki67 with OncotypeDX assay recurrence score [ Designated as safety issue: No ]
  • Identification of a recurrence risk biomarker profile using RNA microarray [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • In situ apoptotic effect of letrozole [ Designated as safety issue: No ]
  • Correlation of the in situ apoptotic effect of letrozole with OncotypeDX assay recurrence score and RNA profiles [ Designated as safety issue: No ]

Estimated Enrollment: 165
Study Start Date: March 2008
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • To determine whether letrozole-induced reduction of Ki67 in postmenopausal women with estrogen receptor (ER)-positive and HER2-negative, resectable, stage I or II breast cancer correlates with the OncotypeDX assay recurrence score.
  • To identify a recurrence risk biomarker profile using RNA microarray.

Secondary

  • To determine the in situ apoptotic effect of letrozole in these patients.
  • To correlate the in situ apoptotic effect of letrozole with OncotypeDX assay recurrence score and RNA profiles.

OUTLINE: Patients receive oral letrozole once daily for 14 days in the absence of disease progression or unacceptable toxicity. No more than 24 hours after the last dose of letrozole, patients undergo total mastectomy or segmental resection with lymph node evaluation.

Patients undergo tumor tissue biopsies at baseline and during surgical resection. Tumor tissue samples are analyzed for Ki67 and caspase 3 by immunohistochemistry; RNA microarray; and OncotypeDX assay (a reverse transcriptase-polymerase chain reaction [RT-PCR] assay of 21 prospectively selected genes).

  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 or II (T1c or T2, N0 or N1) 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 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

PRIOR CONCURRENT THERAPY:

  • At least 21 days since prior tamoxifen or raloxifene as a preventive agent
  • At least 1 month 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00651976

Locations
United States, Tennessee
Vanderbilt-Ingram Cancer Center - Cool Springs Recruiting
Nashville, Tennessee, United States, 37064
Contact: Ingrid Meszoely     615-322-2391        
Vanderbilt-Ingram Cancer Center at Franklin Recruiting
Nashville, Tennessee, United States, 37064
Contact: Ingrid Meszoely     615-322-2391        
Vanderbilt-Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232-6838
Contact: Clinical Trials Office - Vanderbilt-Ingram Cancer Center     800-811-8480        
Sponsors and Collaborators
Vanderbilt-Ingram Cancer Center
Investigators
Principal Investigator: Ingrid Meszoely, MD Vanderbilt-Ingram Cancer Center
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000592970, VU-VICC-BRE-0776, VU-VICC-IRB-080064
Study First Received: April 2, 2008
Last Updated: August 11, 2009
ClinicalTrials.gov Identifier: NCT00651976     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage I breast cancer
stage II breast cancer

Study placed in the following topic categories:
Skin Diseases
Breast Neoplasms
Letrozole
Aromatase Inhibitors
Hormones
Menopause
Breast Diseases

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

ClinicalTrials.gov processed this record on September 11, 2009