Primary Chemotherapy With Docetaxel-Capecitabine and Doxorubicin-Cyclophosphamide in Breast Cancer
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Breast Cancer Breast Neoplasm |
Drug: Docetaxel - Dose A Drug: Anastrozole Drug: cyclophosphamide Drug: Docetaxel - Dose B Drug: Doxorubicin hydrochloride Drug: Tamoxifen Citrate Drug: Capecitabine - Dose B Drug: Capecitabine - Dose A |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | 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 |
- Number of Participants With Adverse Events [ Time Frame: 6 years ] [ Designated as safety issue: Yes ]Here is the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.
- Overall Clinical Response Rate [ Time Frame: 6 years ] [ Designated as safety issue: No ]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.
- Complementary Deoxyribonucleic Acid (cDNA) Expression [ Time Frame: 6 years ] [ Designated as safety issue: No ]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.
- 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 [ Time Frame: 6 years ] [ Designated as safety issue: No ]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.
| Enrollment: | 30 |
| Study Start Date: | June 2000 |
| Study Completion Date: | January 2008 |
| Primary Completion Date: | January 2008 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Dose A-Cohort 1-Arm 1-Docetaxel & Capecitabine
Docetaxel 75 mg/m^2 intravenous day 1, capecitabine 1000 mg/m^2 orally twice daily day 2-15 for 4 cycles
|
Drug: Docetaxel - Dose A
Dose A-Cohort 1 Docetaxel 75 mg/m^2 intravenous day 1
Other Name: Taxotere/Xeloda
Drug: Anastrozole
1 mg orally daily for five years
Other Name: Arimidex
Drug: cyclophosphamide
600 mg/m^2 will be diluted in 100 mL 0.9% normal saline (NS) and administered intravenously over 30 minutes on day 1
Other Name: Cytoxan
Drug: Doxorubicin hydrochloride
60 mg/m^2 will be administered as a slow intravenous push on day 1
Other Name: Adriamycin
Drug: Tamoxifen Citrate
20 mg/day orally for five years
Other Name: Nolvadex
Drug: Capecitabine - Dose A
capecitabine 1000 mg/m^2 orally twice daily day 2-15 for 4 cycles
|
|
Experimental: Dose B-Cohort 2-Arm 2 Reduced dose-Docetaxel & Capecitabine
Docetaxel 60 mg/m^2 intravenous day 1, capecitabine 937.5 mg/m^2 orally twice daily day 2-15 for 4 cycles
|
Drug: Anastrozole
1 mg orally daily for five years
Other Name: Arimidex
Drug: cyclophosphamide
600 mg/m^2 will be diluted in 100 mL 0.9% normal saline (NS) and administered intravenously over 30 minutes on day 1
Other Name: Cytoxan
Drug: Docetaxel - Dose B
Dose B - Cohort 2 Docetaxel 60 mg/m^2 intravenous day 1
Other Name: Taxotere
Drug: Doxorubicin hydrochloride
60 mg/m^2 will be administered as a slow intravenous push on day 1
Other Name: Adriamycin
Drug: Tamoxifen Citrate
20 mg/day orally for five years
Other Name: Nolvadex
Drug: Capecitabine - Dose B
Dose B - Cohort 2 capecitabine 937.5 mg/m^2 orally twice daily day 2-15
|
Detailed Description:
This phase II trial in patients with stage II and stage III breast cancer will test the feasibility of using cDNA microarray as a measure of a tumor's biological response to chemotherapeutic agents by characterizing the cDNA expression patterns in breast cancer before and after primary chemotherapy. Thirty-six patients receive docetaxel/capecitabine induction chemotherapy followed by surgery and doxorubicin/cyclophosphamide adjuvant therapy (TX/AC). We will determine the response rate of TX induction therapy and the toxicities of the sequential combinations (TX/AC). We will also obtain tumor tissue for correlative biological determinations.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
- INCLUSION CRITERIA:
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.
EXCLUSION CRITERIA:
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).
Contacts and Locations| United States, Maryland | |
| National Naval Medical Center | |
| Bethesda, Maryland, United States, 20889 | |
| Principal Investigator: | JoAnne Zujewski, M.D. | National Cancer Institute (NCI), National Institutes of Health (NIH) |
More Information
Additional Information:
Publications:
| Responsible Party: | Jo Anne Zujewski, M.D., Principal Investigator, National Institutes of Health Clinical Center (CC) |
| ClinicalTrials.gov Identifier: | NCT00005908 History of Changes |
| Obsolete Identifiers: | NCT00020241 |
| Other Study ID Numbers: | 000149, 00-C-0149 |
| Study First Received: | June 13, 2000 |
| Results First Received: | February 14, 2012 |
| Last Updated: | March 13, 2013 |
| Health Authority: | United States: Federal Government |
Keywords provided by National Institutes of Health Clinical Center (CC):
|
cDNA Microarray Stage II and Stage III Breast Cancer Biological Response |
Molecular Profiling Fine Needle Aspirate Breast Cancer |
Additional relevant MeSH terms:
|
Breast Neoplasms Neoplasms Neoplasms by Site Breast Diseases Skin Diseases Cyclophosphamide Fluorouracil Docetaxel Anastrozole Capecitabine Doxorubicin Tamoxifen Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |
Pharmacologic Actions Antirheumatic Agents Therapeutic Uses Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antibiotics, Antineoplastic Antineoplastic Agents, Hormonal Selective Estrogen Receptor Modulators Estrogen Receptor Modulators Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Bone Density Conservation Agents |
ClinicalTrials.gov processed this record on May 16, 2013