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

NCT ID: NCT00651976

Last Updated: 2018-10-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 213 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-03-31
• Study Completion Date: 2018-09-30

Brief Summary

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

treatment

Group Type: EXPERIMENTAL

letrozole

Intervention Type: DRUG

Take by mouth at a dose of 2.5 mg on days 7-21

Blood Collection

Intervention Type: OTHER

Blood used for gene expression analysis and reverse transcriptase-polymerase chain reaction

biopsy/lumpectomy/mastectomy

Intervention Type: PROCEDURE

Tissue collection,Surgery to remove tumor, Tumor tissues used for laboratory biomarker analysis

Interventions

letrozole

Take by mouth at a dose of 2.5 mg on days 7-21

Intervention Type: DRUG

Blood Collection

Blood used for gene expression analysis and reverse transcriptase-polymerase chain reaction

Intervention Type: OTHER

biopsy/lumpectomy/mastectomy

Tissue collection,Surgery to remove tumor, Tumor tissues used for laboratory biomarker analysis

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• 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
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Vanderbilt-Ingram Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Ingrid Meszoely, MD

Associate Professor of Surgery (Surgical Oncology); Clinical Director, Vanderbilt Breast Center; Surgical Oncologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ingrid Meszoely, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt-Ingram Cancer Center

Locations

Emory University

Atlanta, Georgia, United States

Surgical Associates, Inc.

Tulsa, Oklahoma, United States

Allegheny Cancer Center

Pittsburgh, Pennsylvania, United States

Vanderbilt-Ingram Cancer Center, One Hundred Oaks

Nashville, Tennessee, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Countries

United States

Related Links

http://www.vicc.org/ct/

Vanderbilt-Ingram Cancer Center, Find a Clinical Trial

Other Identifiers

P50CA098131

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA068485

Identifier Type: NIH

Identifier Source: secondary_id

View Link

VU-VICC-BRE-0776

Identifier Type: -

Identifier Source: secondary_id

VU-VICC-IRB-080064

Identifier Type: -

Identifier Source: secondary_id

VICC BRE 0776

Identifier Type: -

Identifier Source: org_study_id