Clinical trial NCT00005908
Conditions: Breast Cancer Breast Neoplasm
Keywords: cDNA Microarray Stage II and Stage III Breast Cancer Biological Response Molecular Profiling Fine Needle Aspirate Breast Cancer
Sponsor: National Cancer Institute (NCI)
Start date: 2000-06-01; Completion date: 2008-01-01
Enrollment: 30 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

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.

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.

Arms: arm 1: Docetaxel 75 mg/m\^2 intravenous day 1, capecitabine 1000 mg/m\^2 orally twice daily day 2-15 for 4 cycles arm 2: Docetaxel 60 mg/m\^2 intravenous day 1, capecitabine 937.5 mg/m\^2 orally twice daily day 2-15 for 4 cycles
Interventions: intervention 1: Docetaxel - Dose A intervention 2: Anastrozole intervention 3: cyclophosphamide intervention 4: Docetaxel - Dose B intervention 5: Doxorubicin hydrochloride intervention 6: Tamoxifen Citrate intervention 7: Capecitabine - Dose B intervention 8: Capecitabine - Dose A
Intervention descriptions: intervention 1: Dose A-Cohort 1 Docetaxel 75 mg/m\^2 intravenous day 1 intervention 2: 1 mg orally daily for five years intervention 3: 600 mg/m\^2 will be diluted in 100 mL 0.9% normal saline (NS) and administered intravenously over 30 minutes on day 1 intervention 4: Dose B - Cohort 2 Docetaxel 60 mg/m\^2 intravenous day 1 intervention 5: 60 mg/m\^2 will be administered as a slow intravenous push on day 1 intervention 6: 20 mg/day orally for five years intervention 7: Dose B - Cohort 2 capecitabine 937.5 mg/m\^2 orally twice daily day 2-15 intervention 8: capecitabine 1000 mg/m\^2 orally twice daily day 2-15 for 4 cycles

Protocol documents: