An Exploratory, Open-Label Phase I Pharmacodynamic Study of COX-2 Inhibition With Celecoxib (Celebrex) and Aromatase Activity in Breast Cancer
I. Determine whether celecoxib suppresses aromatase activity in postmenopausal women with
invasive breast cancer planning to undergo surgery.
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
III. Determine whether any observed biological effect of this drug is dose-dependent in
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.
Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Change in aromatase activity levels
From baseline to post-surgery
Memorial Sloan-Kettering Cancer Center
United States: Institutional Review Board
|Memorial Sloan Kettering Cancer Center||New York, New York 10021|