Biomarkers in Women Receiving Chemotherapy & Celecoxib for Stage II or Stage III Breast Cancer Removable by Surgery

NCT ID: NCT00665457

Last Updated: 2023-09-13

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

3 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-04-15

Study Completion Date

2009-07-31

Brief Summary

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RATIONALE: Studying samples of blood and tumor tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer.

PURPOSE: This phase II clinical trial is studying biomarkers and side effects in women receiving chemotherapy and celecoxib for stage II or stage III breast cancer that can be removed by surgery.

Detailed Description

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OBJECTIVES:

* To determine the safety and efficacy of four courses of neoadjuvant chemotherapy comprising docetaxel, capecitabine, and celecoxib followed by doxorubicin hydrochloride, cyclophosphamide, and celecoxib for the treatment of women with resectable stage II or III breast cancer.
* To determine the mRNA and protein levels of thyraidylate synthase (TS), thymidine phosphylase (TP), vascular endothelial growth factor (VEGF), Multi-Drug Resistance Protein 1 (MDR-1), cyclooxygenase-2 (COX-2), and matrix metalloproteinase-2 (MMP-2) in tumor tissue prior to and following treatment.
* To correlate baseline expression of TS, TP, VEGF, MDR, COX-2, and MMP-2 to tumor response measured by physical exam, breast MRI, breast ultrasound, mammography, and pathologic response.
* To determine if polymorphisms in the genes that encode those proteins also correlate with outcome, if a correlation is found between specific molecular markers and clinical outcome.

OUTLINE:

* Neoadjuvant chemotherapy: Patients receive docetaxel IV over 1 hour on days 1, 8, and 15, oral capecitabine twice daily on days 1-14, and oral celecoxib twice daily on days 1-21. Courses repeat every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients then receive doxorubicin hydrochloride IV and cyclophosphamide IV once daily on day 1, oral celecoxib twice daily on days 1-14, and filgrastim subcutaneously once daily on days 3-10. Courses repeat every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Celecoxib is stopped one week prior to surgery.

* Surgery: Patients undergo definitive surgery (either modified radical mastectomy or lumpectomy combined with axillary node dissection). Patients may also undergo adjuvant radiotherapy and hormonal therapy at the discretion of multidisciplinary breast team.

Blood is collected at baseline and examined for genetic polymorphisms associated with functional changes in proteins. Tumor tissue is obtained by needle biopsy at baseline, before the second course of docetaxel/capecitabine/celecoxib, and at surgical resection. Molecular markers and protein expression are assessed by immunohistochemistry using fluorescence-image analysis and real-time reverse-transcriptase PCR.

Patients undergo imaging comprising dynamic MRI, ultrasound, and mammogram at baseline and after the first and second 4 courses of chemotherapy.

Conditions

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Breast Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Celecoxib

•Neoadjuvant chemotherapy: Patients receive docetaxel IV over 1 hour on days 1, 8, and 15, oral capecitabine twice daily on days 1-14, and oral celecoxib twice daily on days 1-21. Courses repeat every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients then receive doxorubicin hydrochloride IV and cyclophosphamide IV once daily on day 1, oral celecoxib twice daily on days 1-14, and filgrastim subcutaneously once daily on days 3-10. Courses repeat every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Celecoxib is stopped one week prior to surgery.

•Surgery: Patients undergo definitive surgery (either modified radical mastectomy or lumpectomy combined with axillary node dissection). Patients may also undergo adjuvant radiotherapy and hormonal therapy at the discretion of multidisciplinary breast team.

Group Type EXPERIMENTAL

filgrastim

Intervention Type BIOLOGICAL

capecitabine

Intervention Type DRUG

celecoxib

Intervention Type DRUG

cyclophosphamide

Intervention Type DRUG

docetaxel

Intervention Type DRUG

doxorubicin hydrochloride

Intervention Type DRUG

gene expression analysis

Intervention Type GENETIC

polymorphism analysis

Intervention Type GENETIC

protein expression analysis

Intervention Type GENETIC

reverse transcriptase-polymerase chain reaction

Intervention Type GENETIC

imaging biomarker analysis

Intervention Type OTHER

immunohistochemistry staining method

Intervention Type OTHER

laboratory biomarker analysis

Intervention Type OTHER

pharmacogenomic studies

Intervention Type OTHER

dynamic contrast-enhanced magnetic resonance imaging

Intervention Type PROCEDURE

needle biopsy

Intervention Type PROCEDURE

neoadjuvant therapy

Intervention Type PROCEDURE

radiomammography

Intervention Type PROCEDURE

ultrasound imaging

Intervention Type PROCEDURE

Interventions

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filgrastim

Intervention Type BIOLOGICAL

capecitabine

Intervention Type DRUG

celecoxib

Intervention Type DRUG

cyclophosphamide

Intervention Type DRUG

docetaxel

Intervention Type DRUG

doxorubicin hydrochloride

Intervention Type DRUG

gene expression analysis

Intervention Type GENETIC

polymorphism analysis

Intervention Type GENETIC

protein expression analysis

Intervention Type GENETIC

reverse transcriptase-polymerase chain reaction

Intervention Type GENETIC

imaging biomarker analysis

Intervention Type OTHER

immunohistochemistry staining method

Intervention Type OTHER

laboratory biomarker analysis

Intervention Type OTHER

pharmacogenomic studies

Intervention Type OTHER

dynamic contrast-enhanced magnetic resonance imaging

Intervention Type PROCEDURE

needle biopsy

Intervention Type PROCEDURE

neoadjuvant therapy

Intervention Type PROCEDURE

radiomammography

Intervention Type PROCEDURE

ultrasound imaging

Intervention Type PROCEDURE

Other Intervention Names

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Neupogen Xeloda Celebrex Cytoxan, Neosar Docefrez, Taxotere Lipodox, Lipodox 50, and Doxil

Eligibility Criteria

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Inclusion Criteria

* Pathologic evidence of invasive breast cancer

* Stage II-III disease
* Resectable disease
* Must have a primary tumor estimated by mammogram, ultrasound or palpation to be ≥ 3 cm and/or palpable axillary nodes \> 1 cm for whom neoadjuvant chemotherapy is appropriate
* ECOG performance status 0-1
* Absolute granulocyte count \> 2,000/mm\^3
* Platelet count \> 100,000/mm\^3
* Serum bilirubin \< 1.5 times upper limit of normal (ULN)
* Serum creatinine \< 1.5 times ULN
* Fertile patients must use effective contraception during and for 3 months after completion of study therapy
* At least 2 weeks since prior treatment with cyclooxygenase (COX)-2 inhibitors

Exclusion Criteria

* Not pregnant or nursing/negative pregnancy test
* No allergies to sulfa medication, aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs)
* No uncontrolled concurrent illness that might jeopardize the patient's ability to receive the chemotherapy program outlined in this protocol, including any of the following:

* Active infection requiring intravenous antibiotics
* Symptomatic congestive heart failure
* Unstable angina pectoris
* Serious, uncontrolled cardiac arrhythmia
* No other prior malignancy except for adequately treated basal cell or squamous cell skin cancer, noninvasive carcinomas, or other cancers from which the patient has been disease-free for at least 5 years
* No prior chemotherapy or radiation therapy for ipsilateral breast cancer
* No concurrent sorivudine or brivudine to treat herpes simplex or herpes zoster viral infections
* No concurrent participation in another therapeutic clinical trial
Minimum Eligible Age

19 Years

Maximum Eligible Age

120 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

University of Nebraska

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Elizabeth C. Reed, MD

Role: PRINCIPAL_INVESTIGATOR

University of Nebraska

Locations

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Unversity of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Countries

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United States

Other Identifiers

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P30CA036727

Identifier Type: NIH

Identifier Source: secondary_id

View Link

0085-04-FB

Identifier Type: -

Identifier Source: org_study_id

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