Celecoxib in Treating Postmenopausal Women Who Are Undergoing Surgery for Invasive Breast Cancer

Study Overview
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Brief Summary
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This randomized phase I trial is studying the side effects of celecoxib in treating postmenopausal women with invasive breast cancer who are scheduled to undergo surgery at Memorial Sloan-Kettering Cancer Center. Celecoxib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine whether celecoxib suppresses aromatase activity in postmenopausal women with invasive breast cancer planning to undergo surgery. SECONDARY OBJECTIVES: I. Correlate celecoxib-mediated inhibition of aromatase activity with levels of cyclooxygenase (COX)-2 and HER-2/neu and estrogen receptor status in these patients. II. Determine the effect of this drug on histology, Ki67, RNA expression profile by microarray analysis, PI3-K, AKT and ERK1/2 MAP kinase activities, and PGE_2 levels in these patients. III. Determine whether any observed biological effect of this drug is dose-dependent in these patients. IV. Identify collateral targets (COX-2-independent) of this drug in these patients. OUTLINE: This is a randomized study. Patients are randomized to 1 of 3 treatment arms. Arm I: Patients receive oral celecoxib twice daily for 1-3 weeks (according to the duration between biopsy and surgery) in the absence of unacceptable toxicity. Arm II: Patients receive a higher dose of oral celecoxib as in arm I. Arm III: Patients do not receive treatment. All patients undergo definitive surgery. PROJECTED ACCRUAL: A total of 75 patients (25 per treatment arm) will be accrued for this study within 2-3 years.

Official Title
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An Exploratory, Open-Label Phase I Pharmacodynamic Study of COX-2 Inhibition With Celecoxib (Celebrex) and Aromatase Activity in Breast Cancer

Conditions
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Stage I Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer

Intervention / Treatment
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* Drug: celecoxib
* Procedure: therapeutic conventional surgery
* Other: pharmacological study
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed invasive breast carcinoma Tumor at least 1 cm by radiologic estimate or physical exam No disease limited to ductal carcinoma in situ only Planning to undergo surgery at Memorial Sloan-Kettering Cancer Center Hormone receptor status: Not specified Female Postmenopausal as defined by at least 1 of the following: No menstrual period within the past 12 months Prior bilateral oophorectomy No known liver disease No renal insufficiency No congestive heart failure No coronary artery disease No history of documented peptic ulcer disease No gastritis No medical condition that would preclude definitive surgery No allergy to NSAIDs or sulfa-containing drugs No connective tissue diseases, including any of the following: Systemic lupus erythematosus Reynaud's disease Scleroderma More than 3 months since prior chemotherapy More than 2 weeks since prior hormone replacement therapy More than 2 weeks since prior tamoxifen More than 2 weeks since prior aromatase inhibitors More than 2 weeks since prior raloxifene More than 2 weeks since prior steroids More than 1 week since prior nonsteroidal anti-inflammatory drugs (NSAIDs) More than 1 week since prior cyclooxygenase (COX)-2 inhibitors No concurrent warfarin No concurrent thiazide or loop diuretics No concurrent COX-2 inhibitors No concurrent NSAIDs

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (celecoxib)<br>Patients receive oral celecoxib twice daily for 1-3 weeks (according to the duration between biopsy and surgery) in the absence of unacceptable toxicity. | Drug: celecoxib<br>* Given orally<br>* Other names: SC-58635;Procedure: therapeutic conventional surgery<br>* Undergo surgery<br>Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;Other: laboratory biomarker analysis<br>* Correlative studies<br>|
| Experimental: Arm II (high-dose celecoxib)<br>Patients receive a higher dose of oral celecoxib as in arm I. | Drug: celecoxib<br>* Given orally<br>* Other names: SC-58635;Procedure: therapeutic conventional surgery<br>* Undergo surgery<br>Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;Other: laboratory biomarker analysis<br>* Correlative studies<br>|
| Active Comparator: Arm III (surgery)<br>Patients do not receive treatment. All patients undergo surgery. | Procedure: therapeutic conventional surgery<br>* Undergo surgery<br>Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in aromatase activity levels |  | From baseline to post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cell proliferation via a marker Ki67 between treatment arms by immunohistochemistry |  | From baseline to post-treatment | 
| Correlation between aromatase activity and levels of COX 2 protein, HER 2/neu and ER status in surgical specimens |  | At post-treatment/surgery | 
| Effect of treatment vs. no treatment on gene expression (mRNA) profile by microarray, kinase activities (PI3, AKT and ERK1/2 MAP kinases) and PGE2 levels |  | At post-treatment/surgery |