| Original Study ID : CDR0000583473 |
| Secondary ID : UNMC-08504 |
| NCT ID : NCT00665457 |
| Brief Title : Biomarkers in Women Receiving Chemotherapy and Celecoxib for Stage II or Stage III Breast Cancer That Can Be Removed by Surgery |
| Official Title : Neoadjuvant Therapy and Biomarker Analysis of Stage II and III Breast Cancer With Docetaxel/Capecitabine and Celecoxib Followed by Doxorubicin/Cyclophosphamide and Celecoxib |
| Brief 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. |
| Source : National Cancer Institute (NCI) |
| 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. |
| Overall Status : Active, not recruiting |
| Start Date : April 2004 |
| Official Title : Phase 2 |
| Phase : Interventional |
| Study Design : Treatment, Open Label |
| Enrollment : 46 |
| Verification Date : April 2008 |
| First Received Date : April 22, 2008 |
| Trial Eligibility |
| Criteria : DISEASE CHARACTERISTICS: - 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 - Hormone receptor status not specified PATIENT CHARACTERISTICS: - Menopausal status not specified - 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 - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 3 months after completion of study therapy - 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 PRIOR CONCURRENT THERAPY: - No prior chemotherapy or radiation therapy for ipsilateral breast cancer. - At least 2 weeks since prior treatment with cyclooxygenase (COX)-2 inhibitors - No concurrent sorivudine or brivudine to treat herpes simplex or herpes zoster viral infections - No concurrent participation in another therapeutic clinical trial |
| Gender : Female |
| Minimum Age : 19 Years |
| Maximum Age : N/A |
| Healthy Volunteers : No |
| OutComes |
| Primary OutComes |
| Interventions |
| Type : Biological |
| Name : filgrastim |
| Type : Drug |
| Name : capecitabine |
| Type : Drug |
| Name : celecoxib |
| Type : Drug |
| Name : cyclophosphamide |
| Type : Drug |
| Name : docetaxel |
| Type : Drug |
| Name : doxorubicin hydrochloride |
| Type : Genetic |
| Name : gene expression analysis |
| Type : Genetic |
| Name : polymorphism analysis |
| Type : Genetic |
| Name : protein expression analysis |
| Type : Genetic |
| Name : reverse transcriptase-polymerase chain reaction |
| Type : Other |
| Name : imaging biomarker analysis |
| Type : Other |
| Name : immunohistochemistry staining method |
| Type : Other |
| Name : laboratory biomarker analysis |
| Type : Other |
| Name : pharmacogenomic studies |
| Type : Procedure |
| Name : dynamic contrast-enhanced magnetic resonance imaging |
| Type : Procedure |
| Name : needle biopsy |
| Type : Procedure |
| Name : neoadjuvant therapy |
| Type : Procedure |
| Name : radiomammography |
| Type : Procedure |
| Name : ultrasound imaging |
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