Exemestane With Celecoxib as Neoadjuvant Treatment in Postmenopausal Women With Stage II, III, and IV Breast Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase II Trial of Exemestane (Aromasin) in Combination With Celecoxib (Celebrex) as Neoadjuvant Treatment in Postmenopausal Women With Stage II, III, and IV Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Exemestane
* Drug: Celecoxib
* Other: Correlative studies


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exemestane & Celecoxib<br>Patients will receive 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. | Drug: Exemestane<br>* 25 mg orally once per day for 16 weeks.<br>* Other names: Aromasin;Drug: Celecoxib<br>* 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.<br>* Other names: Celebrex;Other: Correlative studies<br> <br> * Other names: tissue samples;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | up to 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | up to 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Post-Menopause, Neoadjuvant Therapy