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

The Ohio State University

Status and phase: Completed; Phase 2

Conditions: Breast Cancer

Treatments: Drug: Exemestane; Other: Correlative studies; Drug: Celecoxib

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00201773

OSU-0245

Details and patient eligibility

About

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.

Full 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.

Enrollment: 22 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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22 participants in 1 patient group

Exemestane & Celecoxib

Experimental group

Description:

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.

Treatment:

Drug: Celecoxib

Other: Correlative studies

Drug: Exemestane