An Exploratory, Open-Label Phase I Pharmacodynamic Study of COX-2 Inhibition With Celecoxib (Celebrex) and Aromatase Activity in Breast Cancer
18 Years
N/A
Female
Stage I Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer
Trial Information
An Exploratory, Open-Label Phase I Pharmacodynamic Study of COX-2 Inhibition With Celecoxib (Celebrex) and Aromatase Activity in Breast Cancer
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.
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Change in aromatase activity levels
Outcome Time Frame:
From baseline to post-surgery
Safety Issue:
No
Principal Investigator
Elisa Port
Investigator Role:
Principal Investigator
Investigator Affiliation:
Memorial Sloan-Kettering Cancer Center
Authority:
United States: Institutional Review Board
Study ID:
NCI-2012-01441
NCT ID:
NCT00070057
Start Date:
April 2003
Completion Date:
Related Keywords:
- Stage I Breast Cancer
- Stage II Breast Cancer
- Stage IIIA Breast Cancer
- Stage IIIB Breast Cancer
- Stage IIIC Breast Cancer
- Breast Neoplasms
Name | Location |
|---|---|
| Memorial Sloan Kettering Cancer Center | New York, New York 10021 |
