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

August 21, 2023 updated by: University of Nebraska

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

3

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • Unversity of Nebraska Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Drug: cyclophosphamide
Other Names:
  • Cytoxan, Neosar
Genetic: gene expression analysis
Genetic: polymorphism analysis
Drug: docetaxel
Other Names:
  • Docefrez, Taxotere
Genetic: protein expression analysis
Other: laboratory biomarker analysis
Procedure: dynamic contrast-enhanced magnetic resonance imaging
Other: pharmacogenomic studies
Procedure: neoadjuvant therapy
Genetic: reverse transcriptase-polymerase chain reaction
Drug: doxorubicin hydrochloride
Other Names:
  • Lipodox, Lipodox 50, and Doxil
Other: imaging biomarker analysis
Biological: filgrastim
Other Names:
  • Neupogen
Drug: capecitabine
Other Names:
  • Xeloda
Other: immunohistochemistry staining method
Drug: celecoxib
Other Names:
  • Celebrex
Procedure: ultrasound imaging
Procedure: needle biopsy
Procedure: radiomammography

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Grade 4 Adverse Events
Time Frame: every 3 weeks X 4, then every 2 weeks X4
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
Participants Who Experienced Pathologic Complete Response, Progression-free and Overall Survival, and Time to Treatment Failure
Time Frame: 20 weeks
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Nebraska

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Elizabeth C. Reed, MD, University of Nebraska

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 15, 2004

Primary Completion (Actual)

July 31, 2009

Study Completion (Actual)

July 31, 2009

Study Registration Dates

First Submitted

April 22, 2008

First Submitted That Met QC Criteria

April 22, 2008

First Posted (Estimated)

April 23, 2008

Study Record Updates

Last Update Posted (Actual)

September 13, 2023

Last Update Submitted That Met QC Criteria

August 21, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0085-04-FB
  • P30CA036727 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe