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

NCT00073073 | Completed Phase 2 Results

• 2 other identifiers: 04004404-C-0044
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 2

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.

Conditions

Breast Neoplasms

Keywords

Chemoprevention; Mammographic Density; Bone Mineral Density; Biomarkers; Safety; Breast Cancer; Postmenopausal

Outcome Measures

Primary Outcomes (1)

• Percent Change in Mammographic Density at 1 Year on Exemestane

  1 year

Secondary Outcomes (7)

• Effect of This Drug on Bone Mineral Density

  1 year

• Change in Breast Density at 2 Years

  2 years

• Effect of This Drug on Serum Hormones, Insulin-like Growth Factor Pathway Components, and Leptin at 3 Months and 1 Year

  3 months and 1 year

• Absolute Change of Lipid Profiles on Exemestane From Baseline

  1 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 Year

  1 year

Study Arms (1)

Exemestane

EXPERIMENTAL

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.

Drug: Exemestane; Dietary Supplement: Calcium carbonate; Dietary Supplement: Vitamin D

Interventions

Exemestane DRUG

exemestane 25 mg by mouth (PO) every day for two years

Also known as: Aromasin

Exemestane

Calcium carbonate DIETARY_SUPPLEMENT

calcium carbonate 1200 mg PO every day x 2 years

Exemestane

Vitamin D DIETARY_SUPPLEMENT

Vitamin D 400 international units PO every day x 2 years

Exemestane

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Georgetown University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Lombardi Cancer Center, Georgetown University

Washington D.C., District of Columbia, 20007, United States

Location

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, Vogel V, Robidoux A, Dimitrov N, Atkins J, Daly M, Wieand S, Tan-Chiu E, Ford L, Wolmark N. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 1998 Sep 16;90(18):1371-88. doi: 10.1093/jnci/90.18.1371.

  PMID: 9747868 BACKGROUND

• Baum M, Budzar AU, Cuzick J, Forbes J, Houghton JH, Klijn JG, Sahmoud T; ATAC Trialists' Group. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet. 2002 Jun 22;359(9324):2131-9. doi: 10.1016/s0140-6736(02)09088-8.

  PMID: 12090977 BACKGROUND

• Jones S, Vogel C, Arkhipov A, Fehrenbacher L, Eisenberg P, Cooper B, Honig S, Polli A, Whaley F, di Salle E, Tiffany J, Consonni A, Miller L. Multicenter, phase II trial of exemestane as third-line hormonal therapy of postmenopausal women with metastatic breast cancer. Aromasin Study Group. J Clin Oncol. 1999 Nov;17(11):3418-25. doi: 10.1200/JCO.1999.17.11.3418.

  PMID: 10550136 BACKGROUND

• Gatti-Mays ME, Venzon D, Galbo CE, Singer A, Reynolds J, Makariou E, Kallakury B, Heckman-Stoddard BM, Korde L, Isaacs C, Warren R, Gallagher A, Eng-Wong J. Exemestane Use in Postmenopausal Women at High Risk for Invasive Breast Cancer: Evaluating Biomarkers of Efficacy and Safety. Cancer Prev Res (Phila). 2016 Mar;9(3):225-33. doi: 10.1158/1940-6207.CAPR-15-0269. Epub 2016 Jan 12.

  PMID: 26758879 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Breast Neoplasms

Interventions

exemestane; Calcium Carbonate; Vitamin D

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Calcium Compounds; Inorganic Chemicals; Carbonates; Carbonic Acid; Carbon Compounds, Inorganic; Minerals; Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Claudine Isaacs
• Organization: Georgetown University

isaacsc@georgetown.edu

(202)444-3677

Study Officials

• Suparna B Wedam, M.D.

  National Cancer Institute, National Institutes of Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2003
• First Posted: November 17, 2003
• Study Start: November 1, 2003
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: May 17, 2016
• Results First Posted: May 17, 2016

Record last verified: 2015-10

Locations

US (2)