Primary Chemotherapy With Docetaxel-Capecitabine and Doxorubicin-Cyclophosphamide in Breast Cancer
A Pilot Trial of Sequential Primary (Neoadjuvant) Combination Chemotherapy With Docetaxel/Capecitabine (TX) and Doxorubicin/Cyclophosphamide (AC) in Primary Breast Cancer With Evaluation of Chemotherapy Effects on Gene Expression
2 other identifiers
interventional
30
1 country
1
Brief Summary
This study will assess the usefulness of a technique called complementary deoxyribonucleic acid (cDNA) microarray-an examination of a wide array of genes to identify disease-associated patterns-for measuring tumor response to chemotherapy in breast cancer patients. The study will look for "markers" that can help select the most effective type of chemotherapy. It will also evaluate the safety and effectiveness of a new drug combination of capecitabine and docetaxel. Patients age 18 years and older with stage II or III breast cancer whose tumor is 2 centimeters or larger may be eligible for this study. Those enrolled will be treated with surgery, standard chemotherapy using doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan), and the capecitabine and docetaxel combination. Patients will have a physical examination, mammogram and magnetic resonance imaging to evaluate their tumor before beginning treatment. They will then have four 21-day treatment cycles of docetaxel and capecitabine, as follows: docetaxel intravenously (through a vein) on day 1 and capecitabine pills (by mouth) twice a day from days 2 through 15. No drugs will be given from days 16 through 21. This regimen will be repeated four times, after which the tumor will be re-evaluated by physical examination, mammogram, and magnetic resonance imaging. Patients will then have surgery to remove the cancer-either lumpectomy with removal of the underarm lymph nodes; mastectomy and removal of the underarm lymph nodes; or modified radical mastectomy. After recovery, they will have four more cycles of chemotherapy, this time with a doxorubicin and cyclophosphamide. Both drugs will be given intravenously on day 1 of four 21-day cycles. Some patients who had a mastectomy (depending on their tumor characteristics and whether tumor cells were found in their lymph nodes) and all those who had a lumpectomy will also have radiation therapy. Patients with hormone receptor-positive tumors will also receive tamoxifen treatment for 5 years. In addition to the above procedures, all patients will have tumor biopsies (removal of a small piece of tumor tissue) before beginning treatment, on day 1 of cycle 1, before cycle 2, and at the time of surgery, and physical examinations, chest X-rays, bone scans, computerized tomography (CT) scans, electrocardiograms, multi-gated acquisition scan-MUGA (nuclear medicine test of cardiac function) or echocardiograms of heart function, mammograms and blood tests at various times during the study. Patients will be followed at National Institutes of Health (NIH) for 3 years after diagnosis with physical examinations, blood tests, X-rays, and computed tomography (CT) scans. Although it is not known whether this treatment will help an individual patient's cancer, possible benefits are tumor shrinkage and decreased risk of disease recurrence. In addition, the information gained about genetic changes after chemotherapy will help determine if additional studies on the use of cDNA microarray to measure tumor response are warranted.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2 breast-cancer
Started Jun 2000
Longer than P75 for phase_2 breast-cancer
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 1, 2000
CompletedFirst Submitted
Initial submission to the registry
June 13, 2000
CompletedFirst Posted
Study publicly available on registry
June 14, 2000
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2008
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2008
CompletedResults Posted
Study results publicly available
August 27, 2012
CompletedMarch 19, 2013
March 1, 2013
7.6 years
June 13, 2000
February 14, 2012
March 13, 2013
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Number of Participants With Adverse Events
Here is the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.
6 years
Overall Clinical Response Rate
Overall response rate is defined as the percentage of participants with a CR (complete disappearance of all target lesions), PR (a 30% decrease in the sum of the longest diameter of target lesions) determined by clinical measurements per the Response Evaluation Criteria in Solid Tumors (RECIST) and/or a complete pathologic response (disappearance of all invasive tumor pathologically or presence of ductal carcinoma in situ) per the Chevallier criteria. For details about the RECIST or Chevallier criteria see the protocol link module.
6 years
Complementary Deoxyribonucleic Acid (cDNA) Expression
Patients were classified as responders or non-responders based on change in tumor size by clinical exam and pathologic response.For instance, patients with a pathological complete response, micro-invasive disease at surgery, or clinical complete response after four cycles of treatment were considered responders. Changes in gene expression associated with treatment was assessed before/after chemotherapy. All gene expression summary intensities below 50 were thresholded to the value of 50 and genes showing variability significantly smaller than the median gene variability were screened out.
6 years
Number of Participants, e.g. Responders and Non-responders With a Percent Change in Expression Patterns After Chemotherapy With Changes in Expression Patterns After Chemotherapy in Preclinical Models
Patients were classified as responders or non-responders based on change in tumor size by clinical exam and pathologic response.For instance, patients with a pathological complete response, micro-invasive disease at surgery, or clinical complete response after four cycles of treatment were considered responders. Changes in gene expression associated with treatment was assessed before/after chemotherapy. All gene expression summary intensities below 50 were thresholded to the value of 50 and genes showing variability significantly smaller than the median gene variability were screened out.
6 years
Study Arms (2)
Dose A-Cohort 1-Arm 1-Docetaxel & Capecitabine
EXPERIMENTALDocetaxel 75 mg/m\^2 intravenous day 1, capecitabine 1000 mg/m\^2 orally twice daily day 2-15 for 4 cycles
Dose B-Cohort 2-Arm 2 Reduced dose-Docetaxel & Capecitabine
EXPERIMENTALDocetaxel 60 mg/m\^2 intravenous day 1, capecitabine 937.5 mg/m\^2 orally twice daily day 2-15 for 4 cycles
Interventions
Dose A-Cohort 1 Docetaxel 75 mg/m\^2 intravenous day 1
1 mg orally daily for five years
600 mg/m\^2 will be diluted in 100 mL 0.9% normal saline (NS) and administered intravenously over 30 minutes on day 1
Dose B - Cohort 2 Docetaxel 60 mg/m\^2 intravenous day 1
60 mg/m\^2 will be administered as a slow intravenous push on day 1
20 mg/day orally for five years
Dose B - Cohort 2 capecitabine 937.5 mg/m\^2 orally twice daily day 2-15
capecitabine 1000 mg/m\^2 orally twice daily day 2-15 for 4 cycles
Eligibility Criteria
You may qualify if:
- Stage II or III breast cancer with a tumor size of greater than 2 cm. Patients with a previous biopsy are eligible provided adequate tumor tissue remains for biopsy in this study.
- At least 18 years of age.
- Adequate hematopoietic function as defined by absolute neutrophil count greater than 1200/mm\^3 and platelet count greater than 100,000/mm\^3.
- Adequate renal function as defined by creatinine less than 1.6 mg/dL.
- Adequate hepatic function as defined by total (T.) bilirubin less than 1.4 mg/dL and serum glutamic oxaloacetic transaminase (SGOT)/serum glutamic pyruvic transaminase (SGPT) less than 1.5 times the upper limit of normal and alkaline phosphatase less than 2.5 times upper limit of normal
- Zubrod Performance status 0-2.
You may not qualify if:
- Medical or psychiatric condition that, in the opinion of the Principal Investigator, would preclude chemotherapy administration. Patients may be evaluated by psychiatry or medical subspecialties as appropriate.
- Pregnant or lactating women
- Known bleeding disorders
- Hypersensitivity to Tween 80 (Polysorbate)
- Cardiac ejection fraction below normal limits, myocardial infarction within the past 12 months, or symptomatic arrhythmia requiring medical intervention.
- Prior chemotherapy or hormonal therapy for breast cancer. Patients treated with hormonal chemoprevention (tamoxifen or raloxifene) will be eligible.
- Active malignancy diagnosed within the last 5 years. (Cervical cancer or non-melanomatous skin cancer that has been treated with curative intent will be eligible).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Naval Medical Center
Bethesda, Maryland, 20889, United States
Related Publications (5)
Elledge RM, Gray R, Mansour E, Yu Y, Clark GM, Ravdin P, Osborne CK, Gilchrist K, Davidson NE, Robert N, et al. Accumulation of p53 protein as a possible predictor of response to adjuvant combination chemotherapy with cyclophosphamide, methotrexate, fluorouracil, and prednisone for breast cancer. J Natl Cancer Inst. 1995 Aug 16;87(16):1254-6. doi: 10.1093/jnci/87.16.1254. No abstract available.
PMID: 7563172BACKGROUNDMacGrogan G, Mauriac L, Durand M, Bonichon F, Trojani M, de Mascarel I, Coindre JM. Primary chemotherapy in breast invasive carcinoma: predictive value of the immunohistochemical detection of hormonal receptors, p53, c-erbB-2, MiB1, pS2 and GST pi. Br J Cancer. 1996 Nov;74(9):1458-65. doi: 10.1038/bjc.1996.565.
PMID: 8912545BACKGROUNDHarvey JM, Clark GM, Osborne CK, Allred DC. Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol. 1999 May;17(5):1474-81. doi: 10.1200/JCO.1999.17.5.1474.
PMID: 10334533BACKGROUNDLebowitz PF, Eng-Wong J, Swain SM, Berman A, Merino MJ, Chow CK, Venzon D, Zia F, Danforth D, Liu E, Zujewski J. A phase II trial of neoadjuvant docetaxel and capecitabine for locally advanced breast cancer. Clin Cancer Res. 2004 Oct 15;10(20):6764-9. doi: 10.1158/1078-0432.CCR-04-0976.
PMID: 15501952RESULTKorde LA, Lusa L, McShane L, Lebowitz PF, Lukes L, Camphausen K, Parker JS, Swain SM, Hunter K, Zujewski JA. Gene expression pathway analysis to predict response to neoadjuvant docetaxel and capecitabine for breast cancer. Breast Cancer Res Treat. 2010 Feb;119(3):685-99. doi: 10.1007/s10549-009-0651-3.
PMID: 20012355RESULT
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- JoAnne Zujewski, M.D.
- Organization
- National Cancer Institute, National Institutes of Health
Study Officials
- PRINCIPAL INVESTIGATOR
JoAnne Zujewski, M.D.
National Cancer Institute (NCI), National Institutes of Health (NIH)
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
June 13, 2000
First Posted
June 14, 2000
Study Start
June 1, 2000
Primary Completion
January 1, 2008
Study Completion
January 1, 2008
Last Updated
March 19, 2013
Results First Posted
August 27, 2012
Record last verified: 2013-03