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

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

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.

Study Overview

• Status: Completed
• Conditions: Stage I Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: pharmacological study; Procedure: therapeutic conventional surgery; Drug: celecoxib

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.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (celecoxib); Patients receive oral celecoxib twice daily for 1-3 weeks (according to the duration between biopsy and surgery) in the absence of unacceptable toxicity.	Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Procedure: therapeutic conventional surgery; Undergo surgery; Drug: celecoxib; Given orally; Other Names: Celebrex; SC-58635
Experimental: Arm II (high-dose celecoxib); Patients receive a higher dose of oral celecoxib as in arm I.	Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Procedure: therapeutic conventional surgery; Undergo surgery; Drug: celecoxib; Given orally; Other Names: Celebrex; SC-58635
Active Comparator: Arm III (surgery); Patients do not receive treatment. All patients undergo surgery.	Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Procedure: therapeutic conventional surgery; Undergo surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in aromatase activity levels	From baseline to post-surgery

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in cell proliferation via a marker Ki67 between treatment arms by immunohistochemistry	From baseline to post-treatment
Correlation between aromatase activity and levels of COX 2 protein, HER 2/neu and ER status in surgical specimens	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	At post-treatment/surgery

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Elisa Port, Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start: April 1, 2003
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): February 1, 2010

Study Registration Dates

• First Submitted: October 3, 2003
• First Submitted That Met QC Criteria: October 6, 2003
• First Posted (Estimate): October 7, 2003

Study Record Updates

• Last Update Posted (Estimate): December 29, 2016
• Last Update Submitted That Met QC Criteria: December 28, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Celecoxib
• Other Study ID Numbers: NCI-2012-01441 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); P30CA008748 (U.S. NIH Grant/Contract); CDR0000329919; MSKCC-03027 (Other Identifier: Memorial Sloan-Kettering Cancer Center); N01-CN-35112 (Other Identifier: DCP); N01CN35112 (Other Grant/Funding Number: US NIH Grant/Contract Award Number)