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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00665457
• Other study ID #: 0085-04-FB
• Secondary ID: P30CA036727
• Status: Terminated
• Phase: Phase 2
• Start date: April 15, 2004
• Est. completion date: July 31, 2009

Study information

• Verified date: August 2023
• Source: University of Nebraska
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: July 31, 2009
• Est. primary completion date: July 31, 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 19 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• filgrastim

Drug:
• capecitabine

• celecoxib

• cyclophosphamide

• docetaxel

• doxorubicin hydrochloride

Genetic:
• gene expression analysis

• polymorphism analysis

• protein expression analysis

• reverse transcriptase-polymerase chain reaction

Other:
• imaging biomarker analysis

• immunohistochemistry staining method

• laboratory biomarker analysis

• pharmacogenomic studies

Procedure:
• dynamic contrast-enhanced magnetic resonance imaging

• needle biopsy

• neoadjuvant therapy

• radiomammography

• ultrasound imaging

Locations

Country	Name	City	State
United States	Unversity of Nebraska Medical Center	Omaha	Nebraska

Sponsors (2)

Lead Sponsor	Collaborator
University of Nebraska	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Grade 4 Adverse Events	Grading of adverse events was determine by the principal investigator according to NCI common toxicity criteria (CTC version 3.0). Safety analysis is based on any participant experiencing a grade 4 AE.	every 3 weeks X 4, then every 2 weeks X4
Primary	Participants Who Experienced Pathologic Complete Response, Progression-free and Overall Survival, and Time to Treatment Failure	CTEP RECIST guidelines are defined as followed: Pathologic complete response is no signs of residual malignancy cells at the primary site and axillary lymph nodes are seen with histologic examination. Progression-free survival is defined as from the first date of therapy until the first notation of clinical progression or relapse. Overall survival is defined as from the first date of therapy until the date of death. Time to treatment failure is defined as from the first date of therapy until the date the patient is removed from study for any reason.	20 weeks