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

Stage IIIA Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00070057
• Other study ID #: NCI-2012-01441
• Secondary ID: NCI-2012-01441CD
• Status: Completed
• Phase: Phase 1
• First received: October 3, 2003
• Last updated: December 28, 2016
• Start date: April 2003
• Est. completion date: February 2010

Study information

• Verified date: December 2016
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: February 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Stage I Breast Cancer
• Stage II Breast Cancer
• Stage IIIA Breast Cancer
• Stage IIIB Breast Cancer
• Stage IIIC Breast Cancer

Intervention

Drug:
• celecoxib
Given orally

Procedure:
• therapeutic conventional surgery
Undergo surgery

Other:
• pharmacological study
Correlative studies
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in aromatase activity levels		From baseline to post-surgery	No
Secondary	Change in cell proliferation via a marker Ki67 between treatment arms by immunohistochemistry		From baseline to post-treatment	No
Secondary	Correlation between aromatase activity and levels of COX 2 protein, HER 2/neu and ER status in surgical specimens		At post-treatment/surgery	No
Secondary	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	No