Exemestane and Celecoxib in Postmenopausal Women at High Risk for Breast Cancer
| Status: | Completed |
|---|---|
| Conditions: | Breast Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 10/14/2017 |
| Start Date: | November 2003 |
| End Date: | December 2011 |
A Trial of Exemestane in Postmenopausal Women With DCIS or at High Risk for Invasive Breast Cancer
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.
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.
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.
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.
- 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.
We found this trial at
2
sites
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9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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