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

Phase 1

Completed

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

• Registration Number: NCT00070057
• Lead Sponsor: National Cancer Institute (NCI)

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.

Study Timeline

• Study Start: 2003-04
• Study First Submitted: 2003-10-03
• Study First Submitted QC: 2003-10-06
• Study First Posted: 2003-10-07
• Primary Completion: 2010-02
• Study Completion: 2010-02
• Status Verified: 2016-12
• Last Update Submitted: 2016-12-28
• Last Update Posted: 2016-12-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 75

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (celecoxib)	laboratory biomarker analysis	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 III (surgery)	therapeutic conventional surgery	Patients do not receive treatment. All patients undergo surgery.
Arm I (celecoxib)	pharmacological study	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 (high-dose celecoxib)	therapeutic conventional surgery	Patients receive a higher dose of oral celecoxib as in arm I.
Arm II (high-dose celecoxib)	laboratory biomarker analysis	Patients receive a higher dose of oral celecoxib as in arm I.
Arm I (celecoxib)	therapeutic conventional surgery	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 (high-dose celecoxib)	pharmacological study	Patients receive a higher dose of oral celecoxib as in arm I.
Arm III (surgery)	pharmacological study	Patients do not receive treatment. All patients undergo surgery.
Arm III (surgery)	laboratory biomarker analysis	Patients do not receive treatment. All patients undergo surgery.
Arm II (high-dose celecoxib)	celecoxib	Patients receive a higher dose of oral celecoxib as in arm I.
Arm I (celecoxib)	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.

Primary Outcome Measures

Name	Time	Method
Change in aromatase activity levels	From baseline to post-surgery

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Memorial Sloan-Kettering Cancer Center; 🇺🇸 New York, New York, United States