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


Phase 1
18 Years
N/A
Not Enrolling
Female
Stage I Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer

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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