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

National Cancer Institute (NCI)75 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Change in aromatase activity levels

Time frame: From baseline to post-surgery

Secondary Outcomes

Change in cell proliferation via a marker Ki67 between treatment arms by immunohistochemistry

Time frame: From baseline to post-treatment

Correlation between aromatase activity and levels of COX 2 protein, HER 2/neu and ER status in surgical specimens

Time frame: 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