Clinical trial NCT00073073
Conditions: Breast Neoplasms
Keywords: Chemoprevention Mammographic Density Bone Mineral Density Biomarkers Safety Breast Cancer Postmenopausal
Sponsor: Georgetown University
Start date: 2003-11-01; Completion date: 2011-12-01
Enrollment: 46 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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.

Arms: arm 1: exemestane 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.
Interventions: intervention 1: Exemestane intervention 2: Calcium carbonate intervention 3: Vitamin D
Intervention descriptions: intervention 1: exemestane 25 mg by mouth (PO) every day for two years intervention 2: calcium carbonate 1200 mg PO every day x 2 years intervention 3: Vitamin D 400 international units PO every day x 2 years

Protocol documents: