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Biomarkers in Women Receiving Chemotherapy and Celecoxib for Stage II or Stage III Breast Cancer That Can Be Removed by Surgery

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Nebraska
ClinicalTrials.gov Identifier:
NCT00665457
First received: April 22, 2008
Last updated: June 17, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Breast Cancer
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
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University of Nebraska:

Primary Outcome Measures:
  • Safety [ Time Frame: every 3 weeks X 4, then every 2 weeks X4 ] [ Designated as safety issue: Yes ]
  • Efficacy in terms of pathologic complete response, progression-free and overall survival, and time to treatment failure [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
  • Determine mRNA and protein levels of TP, TS, COX-2, MMP-2, MDR-1, and VEGF before and after treatment [ Time Frame: pretreatment and 20 weeks ] [ Designated as safety issue: No ]
  • Correlate baseline expression of TS, TP, VEGF, MDR, COX-2 and MMP-2 to tumor response [ Time Frame: pretreatment and 20 weeks ] [ Designated as safety issue: No ]
  • Correlate specific molecule markers to clinical outcome [ Time Frame: pretreatment and 20 weeks ] [ Designated as safety issue: No ]

Enrollment: 3
Study Start Date: April 2004
Study Completion Date: July 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Celecoxib

•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.

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

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.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00665457

Sponsors and Collaborators
University of Nebraska
Investigators
Principal Investigator: Elizabeth C. Reed, MD University of Nebraska
  More Information

Additional Information:
No publications provided

Responsible Party: University of Nebraska
ClinicalTrials.gov Identifier: NCT00665457     History of Changes
Other Study ID Numbers: 085-04, P30CA036727, UNMC-08504
Study First Received: April 22, 2008
Last Updated: June 17, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Nebraska:
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Capecitabine
Celecoxib
Cyclophosphamide
Docetaxel
Doxorubicin
Liposomal doxorubicin
Alkylating Agents
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antibiotics, Antineoplastic
Antimetabolites
Antimetabolites, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Central Nervous System Agents
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on November 20, 2014