Trial Information

Neoadjuvant Therapy and Biomarker Analysis of Stage II and III Breast Cancer With Docetaxel/Capecitabine and Celecoxib Followed by Doxorubicin/Cyclophosphamide and Celecoxib

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.