Trial record 1 of 5 for:    exemestane high risk
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Exemestane and Celecoxib in Postmenopausal Women at High Risk for Breast Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Georgetown University
ClinicalTrials.gov Identifier:
NCT00073073
First received: November 14, 2003
Last updated: May 7, 2014
Last verified: March 2014
  Purpose

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.

Condition Intervention Phase
Breast Neoplasms
Drug: Exemestane
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Trial of Exemestane in Postmenopausal Women With DCIS or at High Risk for Invasive Breast Cancer

Resource links provided by NLM:


Further study details as provided by Georgetown University:

Primary Outcome Measures:
  • Percent change in mammographic density at 1 year on exemestane [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Effect of this drug on bone mineral density [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Change in breast density at 2 years [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Effect of this drug on serum hormones, insulin-like growth factor pathway components, and leptin at 3 months and 1 year [ Time Frame: 3 months and 1 year ] [ Designated as safety issue: No ]
  • Absolute change of lipid profiles on exemestane from baseline [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Effect of this drug on breast tissue trefoil factor 1 and proliferating cell nuclear antigen expression, prolactin, and breast tissue prolactin receptor at 1 year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Effect of exemestane on autocrine prolactin and breast tissue prolactin receptor at one year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Number of serum and breast tissue samples collected for exploratory proteomic profiles at one year [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Enrollment: 46
Study Start Date: November 2003
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Exemestane
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
Drug: Exemestane
exemestane 25 mg by mouth (PO) every day for two years calcium carbonate 1200 mg PO every day and vitamin D 400 IU PO every day x 2 years
Other Name: Aromasin

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.
  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Postmenopausal female.

Postmenopausal defined as no menses for at least 12 months or bilateral oophorectomy. In unclear cases, (e.g. 50 year old who has had hysterectomy) chemical confirmation of postmenopausal status may be confirmed with follicle stimulating hormone (FSH) greater than 35 U/L.

Elevated risk for developing invasive breast cancer by virtue of one of the following criteria:

Gail Model risk of greater than or equal to 1.7% over 5 years from study entry. (This is the same minimum level of risk required for a subject to be eligible for the recently completed NSABP-P1 tamoxifen breast cancer prevention trial).

Lobular neoplasia.

Atypical ductal hyperplasia.

DCIS (ductal carcinoma in situ) that has been previously treated with mastectomy or lumpectomy and radiation, +/- tamoxifen.

Deleterious mutations in BRCA1 or 2 OR A priori risk assessment of 20% chance or greater of carrying BRCA1/2 gene mutation. The BRCAPRO and Couch model will both be used to asses this risk. If a woman has a 20% risk of carrying a BRCA1/2 mutation by either model, she will meet eligibility criteria.

Prior stage I or II breast cancer at least 2 years out from treatment for invasive disease and no prior use of aromatase inhibitors.

Subjects should be willing to abstain from use of hormonal therapies (e.g. tamoxifen, hormone replacement therapy, oral contraceptive pills, hormone-containing intrauterine devices (IUDs). E-string is acceptable). Venlafaxine will be offered as supportive care for women with menopausal symptoms.

Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

Subject has been counseled regarding her options and has signed the informed consent document.

Baseline dual-emission x-ray absorptiometry (DEXA) scan with bone mineral density (BMD) T-score greater than or equal to 2.5 at antero posterior (AP) spine.

Hemoglobin greater than or equal to 11 g/dl.

Creatinine less than 1.5 times the upper limits of normal.

Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) less than 2.5 times upper limit of normal.

No investigational agent for the past 30 days.

If history of cancer (other than squamous or basal cell skin cancers), subject must have no evidence of disease at time of enrollment AND no history of cancer directed treatment in the 2 years preceding enrollment.

EXCLUSION CRITERIA:

Current or recent chronic use (within 3 months) of hormonal medications, e.g. oral contraceptive pills, hormone replacement therapy, tamoxifen, raloxifene, IUD with progestins or corticosteroids. (Subjects on chronic topical or inhaled steroids will be eligible for the study.) Current use of phenytoin, carbamazepine, rifampin due to increased estrogen metabolism.

History of clotting or bleeding disorder.

History of allergic reactions attributed to compounds of similar chemical or biologic composition to exemestane (e.g. anastrozole, letrozole, formestane).

Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

  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: NCT00073073

Locations
United States, District of Columbia
Lombardi Cancer Center, Georgetown University
Washington, District of Columbia, United States, 20007
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Georgetown University
Investigators
Principal Investigator: Suparna B Wedam, M.D. National Cancer Institute, National Institutes of Health
  More Information

Additional Information:
Publications:
Responsible Party: Georgetown University
ClinicalTrials.gov Identifier: NCT00073073     History of Changes
Obsolete Identifiers: NCT00085072
Other Study ID Numbers: 040044, 04-C-0044
Study First Received: November 14, 2003
Last Updated: May 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Georgetown University:
Chemoprevention
Mammographic Density
Bone Mineral Density
Biomarkers
Safety
Breast Cancer
Postmenopausal

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

ClinicalTrials.gov processed this record on August 28, 2014