Breast Cancer
Conditions
Keywords
Post-Menopause, Neoadjuvant Therapy
Brief summary
To test whether the addition of the COX-2 inhibitor, celecoxib, will decrease the gene expression of CYP19 in breast cancers collected from postmenopausal women that receive neoadjuvant exemestane.
Detailed description
Rationale: In postmenopausal women, the main source of estrogen is through the conversion of androgens, or sex hormones produced by the adrenal glands. An enzyme called aromatase carries out this process. Exemestane, an aromatase inhibitor, blocks production of estrogens. Research indicates that the gene responsible for aromatase activity is CYPO19. Therefore, exemestane helps to inhibit aromatase activity through CYP019. Along with CYP019, another gene associated with breast cancer is an overexpression of COX-2 enzymes. Research suggests that COX-2 overexpression can cause cancer cell division, increased blood flow to tumors, and metastases. Celecoxib blocks COX-2 activity and produces fewer side effects compared with other non-steroidal inflammatory drugs (NSAIDs). This study builds on previous research to test the combination of exemestane and celecoxib for breast cancer. Purpose: This study is evaluating the safety and efficacy of exemestane and celecoxib before surgery for stage II, III, and IV breast cancer in postmenopausal women. Tests will analyze the CYP019 gene after these treatments. Treatment: Patients in this study will receive exemestane and celecoxib. Both drugs will be given to patients as oral pills. Exemestane will be taken daily for sixteen weeks. Starting in week 9, celecoxib will be taken twice daily for eight weeks. Therefore, during weeks 9-16, patients will be taking both exemestane and celecoxib. Several tests and exams will be given throughout the study to closely monitor patients, including a biopsy performed after the first 8 weeks on exemestane. After sixteen weeks on exemestane and celecoxib, patients will have breast surgery.
Interventions
DRUGExemestane
25 mg orally once per day for 16 weeks.
DRUGCelecoxib
given orally at two 200 mg capsules (400 mg) twice per day. Patients assigned to receive 400 mg twice per day should be instructed to take the drug with food.
OTHERCorrelative studies
Sponsors
Pfizer
Ohio State University Comprehensive Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must be female with histologically confirmed breast cancer * Stage II-IV disease * ER and/or PR positive * ECOG Performance Status 0-1 * Tumor must be present following core needle biopsy as determined by physical exam or radiographic evaluation. * Postmenopausal * No prior treatment for current breast cancer. No other active malignancy is allowed.Adequately treated basal cell, squamous cell skin cancer, in situ cervical cancer, or any other cancer from which the patient has been disease-free for 5 years is permitted. Biphosphonates and palliative radiation for bone metastasis is permitted while on study. * Hormone replacement therapy must be discontinued. It is not permitted during the time on study.
Exclusion criteria
* Known history of aspirin or NSAID induced asthma, urticaria or allergic reactions; or allergy to sulfonamides severe enough in nature to require emergency room treatment or hospitalization. * History of myocardial infarction or other thrombotic events. * Inflammatory breast cancer (edema or ulceration of the skin of the breast). * Significant renal dysfunction (serum creatinine \> 1.5 x upper limit of normal). * Significant hepatic dysfunction (serum bilirubin \> 1.5 x upper limit of normal or AST, ALT \> 3 x upper limit of normal) * ANC \<1.5, platelets \<100,000 K/uL, and hemoglobin \< 9 g/dL. * Use of other COX-2 inhibitors such as rofecoxib (Vioxx®, aspirin, trisalicylate (Trilisate®), is not permitted during the time on study. No washout period is required. Baby aspirin, 81 mg po daily, is permitted. * Use of NSAID's such as ibuprofen (Advil® or Motrin®), naproxyn (Aleve® Naprosyn®, or Anaprox®), etodolac (Lodine®), oxaprozin (Daypro®), difusanil (Dolobid®), nabumetone (Relafin®), or tolmetin (Tolectin®) is not permitted during the time on study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Decreased Gene Expression of CYP19 in Breast Cancer by Adding COX-2 Inhibitor to Exemestane | up to 16 weeks | Collected from postmenopausal women that receive neoadjuvant exemestane. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate Response Rate of Neoadjuvant Exemestane and Celecoxib in Postmenopausal Women. | up to 16 weeks | Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response, Disappearance of all target lesions; Partial Response, \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease, \<30% decrease in the sum of the longest diameter of target lesions; Progressive Disease, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. |
Countries
United States
Participant flow
Recruitment details
Enrollment of postmenopausal women between January 2003 and July 2007
Participants by arm
| Arm | Count |
|---|---|
| Exemestane & Celecoxib Patients will received exemestane 25 mg orally per day for 8 weeks. Starting in the 9th week, patients will receive celecoxib 400 mg orally twice per day for 8 weeks in addition to exemestane.
Exemestane: 25 mg orally once per day for 16 weeks.
Celecoxib: given orally at two 200 mg capsules (400 mg) twice per day. Patients assigned to receive 400 mg twice per day and instructed to take the drug with food.
Correlative studies | 22 |
| Total | 22 |
Baseline characteristics
| Characteristic | Exemestane & Celecoxib |
|---|---|
| Age, Continuous | 63 years |
| Axillary Nodal Evaluation Fine needle aspiration | 2 patients |
| Axillary Nodal Evaluation Sentinel | 1 patients |
| Clinical Axillary Status Negative | 15 patients |
| Clinical Axillary Status Positive | 7 patients |
| Clinical Stage I (cancer cells confined to limited area) | 1 patients |
| Clinical Stage IIA (evidence cancer has begun to grow/spread) | 14 patients |
| Clinical Stage IIB (tumor between 2-5 cm or larger) | 3 patients |
| Clinical Stage IIIA (cancer considered advanced) | 3 patients |
| Clinical Stage Occult primary (axillary metastases) | 1 patients |
| ECOG (Eastern Cooperative Oncology Group) Performance Status 0-1 | 22 patients |
| Her-2 FISH Negative | 8 patients |
| Her-2 FISH Not available | 10 patients |
| Her-2 FISH Positive | 4 patients |
| Histology Invasive | 15 patients |
| Histology Lobular | 5 patients |
| Histology Mixed invasive and lobular | 2 patients |
| Menopause Status of Postmenopausal | 22 patients |
| Progesterone Receptor status Negative | 6 patients |
| Progesterone Receptor status Positive | 16 patients |
| Region of Enrollment United States | 22 patients |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 22 / 22 | 22 / 22 |
| serious Total, serious adverse events | 0 / 22 | 0 / 22 |
Outcome results
Primary
Number of Patients With Decreased Gene Expression of CYP19 in Breast Cancer by Adding COX-2 Inhibitor to Exemestane
Collected from postmenopausal women that receive neoadjuvant exemestane.
Time frame: up to 16 weeks
Population: Comparison of immunohistochemistry (IHC) Allred Differences with Neoadjuvant Therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exemestane + Celecoxib | Number of Patients With Decreased Gene Expression of CYP19 in Breast Cancer by Adding COX-2 Inhibitor to Exemestane | 0 patients |
| Exemestane | Number of Patients With Decreased Gene Expression of CYP19 in Breast Cancer by Adding COX-2 Inhibitor to Exemestane | 0 patients |
Secondary
Evaluate Response Rate of Neoadjuvant Exemestane and Celecoxib in Postmenopausal Women.
Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response, Disappearance of all target lesions; Partial Response, \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease, \<30% decrease in the sum of the longest diameter of target lesions; Progressive Disease, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: up to 16 weeks
Population: Clinical Response was determined by physical exam and breast Ultrasound at baseline and repeated at 8 weeks and 16 weeks, and pathological response by histopathological examination of primary tumor and axillary nodes after definitive breast cancer surgery.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Exemestane + Celecoxib | Evaluate Response Rate of Neoadjuvant Exemestane and Celecoxib in Postmenopausal Women. | Partial Response | 5 patients |
| Exemestane + Celecoxib | Evaluate Response Rate of Neoadjuvant Exemestane and Celecoxib in Postmenopausal Women. | Stable Disease | 1 patients |
| Exemestane + Celecoxib | Evaluate Response Rate of Neoadjuvant Exemestane and Celecoxib in Postmenopausal Women. | Complete Response | 0 patients |
| Exemestane + Celecoxib | Evaluate Response Rate of Neoadjuvant Exemestane and Celecoxib in Postmenopausal Women. | Progressive Disease | 1 patients |
| Exemestane + Celecoxib | Evaluate Response Rate of Neoadjuvant Exemestane and Celecoxib in Postmenopausal Women. | Non-measurable | 15 patients |