NCT00665457

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

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

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 3 (actual)
• Sponsor: University of Nebraska · Academic / Other
• Sex: Female
• Age: 19 Years – 120 Years
• Healthy volunteers: Not accepted

Summary

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

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

• Breast Cancer

Interventions

Type	Name	Description
BIOLOGICAL	filgrastim
DRUG	capecitabine
DRUG	celecoxib
DRUG	cyclophosphamide
DRUG	docetaxel
DRUG	doxorubicin hydrochloride
GENETIC	gene expression analysis
GENETIC	polymorphism analysis
GENETIC	protein expression analysis
GENETIC	reverse transcriptase-polymerase chain reaction
OTHER	imaging biomarker analysis
OTHER	immunohistochemistry staining method
OTHER	laboratory biomarker analysis
OTHER	pharmacogenomic studies
PROCEDURE	dynamic contrast-enhanced magnetic resonance imaging
PROCEDURE	needle biopsy
PROCEDURE	neoadjuvant therapy
PROCEDURE	radiomammography
PROCEDURE	ultrasound imaging

Timeline

• Start date: 2004-04-15
• Primary completion: 2009-07-31
• Completion: 2009-07-31
• First posted: 2008-04-23
• Last updated: 2023-09-13
• Results posted: 2018-07-10

Locations

1 site across 1 country: United States