Clinical trial NCT00070057: Celecoxib in Treating Postmenopausal Women Who Are Undergoing Surgery for Invasive Breast Cancer
Official title: An Exploratory, Open-Label Phase I Pharmacodynamic Study of COX-2 Inhibition With Celecoxib (Celebrex) and Aromatase Activity in Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Stage I Breast Cancer
Stage II Breast Cancer
Stage IIIA Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-10-07
Enrollment: 75
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in aromatase activity levels
timeFrame: From baseline to post-surgery
Secondary outcomes:
measure: Change in cell proliferation via a marker Ki67 between treatment arms by immunohistochemistry
timeFrame: From baseline to post-treatment
measure: Correlation between aromatase activity and levels of COX 2 protein, HER 2/neu and ER status in surgical specimens
timeFrame: At post-treatment/surgery
measure: 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
timeFrame: At post-treatment/surgery
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Elisa Port
role: PRINCIPAL_INVESTIGATOR
References: