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

University of Nebraska

Status and phase

Terminated

Phase 2

Conditions

Breast Cancer

Treatments

Drug: docetaxel

Procedure: neoadjuvant therapy

Procedure: needle biopsy

Genetic: gene expression analysis

Drug: doxorubicin hydrochloride

Other: laboratory biomarker analysis

Other: imaging biomarker analysis

Procedure: radiomammography

Drug: capecitabine

Other: immunohistochemistry staining method

Biological: filgrastim

Procedure: ultrasound imaging

Drug: celecoxib

Genetic: polymorphism analysis

Genetic: reverse transcriptase-polymerase chain reaction

Procedure: dynamic contrast-enhanced magnetic resonance imaging

Other: pharmacogenomic studies

Genetic: protein expression analysis

Drug: cyclophosphamide

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00665457

P30CA036727 (U.S. NIH Grant/Contract)

0085-04-FB

Details and patient eligibility

About

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.

Full description

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.

Enrollment

3 patients

Sex

Female

Ages

19 to 120 years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

3 participants in 1 patient group

Celecoxib

Experimental group

Description:

•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.

Treatment: