Breast CancerPhase 2NCT00665457
Biomarkers in Women Receiving Chemotherapy & Celecoxib for Stage II or Stage III Breast Cancer Removable by Surgery
A Phase 2 study testing filgrastim, capecitabine and celecoxib in people with Breast Cancer, run by University of Nebraska at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 19 to 120 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- filgrastim, capecitabine and celecoxib
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Apr 2004to 31 Jul 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 120 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 11Show fewer
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Unversity of Nebraska Medical Center
Omaha, Nebraska, 68198
About this study
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
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.
Read the 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
- Being tested
- filgrastim, capecitabine, celecoxib, cyclophosphamide, docetaxel
- Keywords
- stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
filgrastimBiological
Also called Neupogen
capecitabineDrug
Also called Xeloda
celecoxibDrug
Also called Celebrex
cyclophosphamideDrug
Also called Cytoxan, Neosar
docetaxelDrug
Also called Docefrez, Taxotere
Also called Lipodox, Lipodox 50, and Doxil
gene expression analysisGenetic
polymorphism analysisGenetic
protein expression analysisGenetic
reverse transcriptase-polymerase chain reactionGenetic
imaging biomarker analysisOther
laboratory biomarker analysisOther
pharmacogenomic studiesOther
dynamic contrast-enhanced magnetic resonance imagingProcedure or surgery
needle biopsyProcedure or surgery
neoadjuvant therapyProcedure or surgery
radiomammographyProcedure or surgery
ultrasound imagingProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| Celecoxib | Experimental | •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. Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 20 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2008 (estimated)
- Study start15 Apr 2004
- Primary completion31 Jul 2009
- Study completion31 Jul 2009
Why it stopped: study drug was removed from the market and low enrollment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by University of NebraskaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Elizabeth C. Reed, MD, Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00665457
- Sponsor's protocol ID
- 0085-04-FB
- Other IDs
- P30CA036727
- Status last verified
- Aug 2023
- First submitted
- 22 Apr 2008
- Last updated
- 13 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00665457
- Acronym / sponsor ID
- 0085-04-FB
- Conditions
- Breast Cancer
- Keywords
- stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: study drug was removed from the market and low enrollment.
- Enrolment
- 3 participants (actual)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 15 Apr 2004 (actual)
- Primary completion
- 31 Jul 2009 (actual)
- Study completion
- 31 Jul 2009 (actual)
- First posted
- 23 Apr 2008 (estimated)
- Results
- Posted 10 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Celecoxib | Experimental | 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•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. |
Who may qualify
- Ages
- 19 to 120 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Pathologic evidence of invasive breast cancer
- 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
Key exclusion criteria (11 listed)
- 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:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| filgrastimAlso: Neupogen | Biological | Celecoxib |
| capecitabineAlso: Xeloda | Drug | Celecoxib |
| celecoxibAlso: Celebrex | Drug | Celecoxib |
| cyclophosphamideAlso: Cytoxan, Neosar | Drug | Celecoxib |
| docetaxelAlso: Docefrez, Taxotere | Drug | Celecoxib |
| doxorubicin hydrochlorideAlso: Lipodox, Lipodox 50, and Doxil | Drug | Celecoxib |
| gene expression analysis | Genetic | Celecoxib |
| polymorphism analysis | Genetic | Celecoxib |
| protein expression analysis | Genetic | Celecoxib |
| reverse transcriptase-polymerase chain reaction | Genetic | Celecoxib |
| imaging biomarker analysis | Other | Celecoxib |
| immunohistochemistry staining method | Other | Celecoxib |
| laboratory biomarker analysis | Other | Celecoxib |
| pharmacogenomic studies | Other | Celecoxib |
| dynamic contrast-enhanced magnetic resonance imaging | Procedure or surgery | Celecoxib |
| needle biopsy | Procedure or surgery | Celecoxib |
| neoadjuvant therapy | Procedure or surgery | Celecoxib |
| radiomammography | Procedure or surgery | Celecoxib |
| ultrasound imaging | Procedure or surgery | Celecoxib |
Primary outcome
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Breast Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elizabeth C. Reed, MD principal investigator
University of Nebraska
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing filgrastim, capecitabine and celecoxib in people with Breast Cancer, run by University of Nebraska at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Grade 4 Adverse Events (time frame: every 3 weeks X 4, then every 2 weeks X4). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2023.