Clinical trial NCT01869192
Conditions: Malignant Neoplasm of Female Breast
Keywords: Malignant Neoplasm Cancer Female Breast Stage II Stage III
Sponsor: University of Colorado, Denver
Start date: 2003-03-05; Completion date: 2010-08-21
Enrollment: 72 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
A primary objective of this study is to evaluate the in vivo response of tumor to chemotherapy through gene microarray analysis. Neoadjuvant treatment allows the unique opportunity to observe the in vivo effects of cytotoxic therapy on gene expression in tumor tissue. The investigators plan to evaluate several different questions by comparing gene profiles in different phases of treatment in this study. These are outlined below.

Hypotheses

1. Chemotherapy enriches for tumor cell populations that have enhanced resistance and survival mechanisms. These mechanisms will in part be identifiable through changes in gene expression profiles pre vs. post treatment.
2. Use of two distinct chemotherapy selection pressures, for example a DNA-damaging regimen (epirubicin and cyclophosphamide) or a mitotic spindle/metabolic targeted regimen (docetaxel and capecitabine), will allow for the identification of a smaller set of genes associated to resistance and survival mechanisms of broad importance.
3. Genes associated with enrichment for resistance and survival mechanisms will not be present in large amounts pretreatment in tumors destined for complete pathologic response.

Detailed description:
The clinical outcomes of breast cancer treatment are remarkably similar regardless of the regimen used, even though the individual drugs may differ substantially in mechanisms of action. We are interested in identifying a set of genes that may be associated with breast cancer cell survival following selection by chemotherapy. We intend to use two different selection pressures (different chemotherapy regimens with different mechanisms of action) in order to focus on those genes that are regulated similarly in response to either regimen.

Neoadjuvant chemotherapy is in common use for locally advanced breast cancers. Although it does not yet appear to impart a survival advantage, it does enhance the likelihood of breast conserving surgery and also provides important prognostic information. Taxotere appears to add significantly to pathologic complete responses when added to doxorubicin and cyclophosphamide alone. The combination of capecitabine and docetaxel was superior to docetaxel alone in metastatic disease. Many investigators are interested in incorporating this regimen for the treatment of earlier stages of breast cancer.

Arms: arm 1: Arm A: Epirubicin 90 mg/m2 day 1 IV and Cyclophosphamide 600 mg/m2 day 1 IV q 3 weeks for 4 cycles, then surgery, then Docetaxel 75 mg/m2 IV day 1 plus Capecitabine 1000 mg/m2/dose po bid x 14 days q 3 weeks for 4 cycles, then radiation therapy as indicated. Post surgical chemotherapy must be initiated within 35 days after completion of definitive surgical treatment arm 2: Arm B: Docetaxel 75 mg/m2 IV day 1 plus Capecitabine 1000 mg/m2/dose po bid x 14 days q 3 weeks for 4 cycles, then surgery, then Epirubicin 90 mg/m2 day 1 IV and Cyclophosphamide 600 mg/m2 day 1 IV q 3 weeks for 4 cycles, then radiation therapy as indicated. Post surgical chemotherapy must be initiated within 35 days after completion of definitive surgical treatment
Interventions: intervention 1: Epirubicin intervention 2: Cyclophosphamide intervention 3: Docetaxel intervention 4: Capecitabine intervention 5: Radiation Therapy
Intervention descriptions: intervention 1: Epirubicin 90 mg/m2 d1 q3w intervention 2: Cyclophosphamide 600 mg/m2 d1 q3w intervention 3: Docetaxel 75 mg/m2 d1 q3w intervention 4: Capecitabine 1000 mg/m2/dose bid x 14d q3w intervention 5: Standard dosing, fields depending on clinical findings

Protocol documents: