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Exemestane and Celecoxib in Postmenopausal Women at High Risk for Breast Cancer

Phase 2
Completed
Conditions
Breast Neoplasms
Interventions
Dietary Supplement: Calcium carbonate
Dietary Supplement: Vitamin D
Registration Number
NCT00073073
Lead Sponsor
Georgetown University
Brief Summary

The primary goal of this 5-year study is to determine whether exemestane alone or in combination with celecoxib decreases breast tissue density in healthy postmenopausal women at high risk for breast cancer. Dense breast tissue seen on mammography has been linked to an increased risk of breast cancer. The study will also examine the effects of exemestane and celecoxib on bone density, blood hormone levels and quality of life. Exemestane, approved by the Food and Drug Administration for treating postmenopausal women with breast cancer, lowers the amount of estrogen in the body. Celecoxib, approved for treating arthritis pain and for reducing the number or colon polyps in an inherited syndrome, is an anti-inflammatory drug. Half of the women in the study will receive exemestane alone and half will receive exemestane and celecoxib together.

In December 2004, the arm using exemestane and celecoxib was closed to accrual

Postmenopausal women who are at increased risk for developing invasive breast cancer may be eligible to participate. Candidates are screened with breast cancer risk assessment, medical history and physical examination, blood tests, review of medical records, if needed, breast biopsy, and dual energy x-ray absorptiometry (DEXA) scan to assess bone density. For the DEXA scan, the subject lies still on a table for about 30 minutes while the spine and hip are scanned using a small amount of radiation.

Participants take exemestane in pill form once a day for 2 years. They also take calcium and vitamin D pills daily to help protect bone health. They are followed in the clinic during the course of the study to determine the amount of drug taken and any side effects, and for the following tests and procedures:

* Medical evaluation and blood tests at after 1 and 3 months on study drugs

* Medical evaluation at 6 months

* Breast biopsy at screening and then at 12 months

* dual-emission x-ray absorptiometry (DEXA) scan of the spine, mammogram and routine blood tests before starting study drugs and then yearly for 5 years.

Detailed Description

Background:

Evidence from adjuvant treatment trials of invasive breast cancer with aromatase inhibitors suggests that these agents are superior to tamoxifen in preventing contralateral breast cancer and are well tolerated. These agents are promising breast cancer chemopreventive agents. Data on safety and effect on surrogate biomarkers in a healthy at risk population is lacking.

Objectives:

Primary:

-The primary objective is to evaluate the study drug effects on mammographic density after one year on treatment.

Secondary:

-Secondary objectives include assessing the effect of the intervention on bone mineral density, serum hormones and lipids, and breast tissue biomarkers.

Eligibility:

Eligible patients are postmenopausal women who meet one of the following criteria:

* History of stage I or II breast cancer 2 years out from definitive therapy.

* Gail model 5 year risk greater than or equal to 1.7%

* History of treated ductal carcinoma in-situ (DCIS)

* History of high risk lesion on breast biopsy (atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), lobular carcinoma in-situ (LCIS))

* Known or suspected breast cancer 1, early onset (BRCA1) or breasts cancer 2, early onset (BRCA2) mutation

* Subjects must have adequate bone mineral density by dual-emission x-ray absorptiometry (DEXA) scan in order to enroll.

Design:

* This is an open label study of exemestane in postmenopausal women with an elevated risk of developing invasive breast cancer. Forty five subjects will be enrolled and receive standard dose exemestane (25 mg each day (QD)), calcium and vitamin D.

* Each subject will continue treatment for a total of two years.

* Changes in mammographic breast density and bone mineral density will be evaluated annually which will provide long term biomarker and safety information about prevention therapy with exemestane.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
46
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
ExemestaneCalcium carbonateexemestane 25 mg by mouth (PO) every day for two years taken with calcium carbonate 1200 mg PO every day and vitamin D 400 IU PO every day Initially patients were initially planned to receive Celecoxib but the study was amended prior to any subject going on and Celecoxib was never administered to any subjects.
ExemestaneVitamin Dexemestane 25 mg by mouth (PO) every day for two years taken with calcium carbonate 1200 mg PO every day and vitamin D 400 IU PO every day Initially patients were initially planned to receive Celecoxib but the study was amended prior to any subject going on and Celecoxib was never administered to any subjects.
ExemestaneExemestaneexemestane 25 mg by mouth (PO) every day for two years taken with calcium carbonate 1200 mg PO every day and vitamin D 400 IU PO every day Initially patients were initially planned to receive Celecoxib but the study was amended prior to any subject going on and Celecoxib was never administered to any subjects.
Primary Outcome Measures
NameTimeMethod
Percent Change in Mammographic Density at 1 Year on Exemestane1 year
Secondary Outcome Measures
NameTimeMethod
Change in Breast Density at 2 Years2 years
Effect of This Drug on Serum Hormones, Insulin-like Growth Factor Pathway Components, and Leptin at 3 Months and 1 Year3 months and 1 year
Effect of This Drug on Bone Mineral Density1 year
Absolute Change of Lipid Profiles on Exemestane From Baseline1 year
Effect of This Drug on Breast Tissue Trefoil Factor 1 and Proliferating Cell Nuclear Antigen Expression, Prolactin, and Breast Tissue Prolactin Receptor at 1 Year1 year
Effect of Exemestane on Autocrine Prolactin and Breast Tissue Prolactin Receptor at One Year1 year
Number of Serum and Breast Tissue Samples Collected for Exploratory Proteomic Profiles at One Year1 year

Trial Locations

Locations (2)

Lombardi Cancer Center, Georgetown University

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Washington, District of Columbia, United States

National Institutes of Health Clinical Center, 9000 Rockville Pike

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Bethesda, Maryland, United States

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