Conditions: Breast Cancer Metastatic Breast Cancer
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 21
Healthy volunteers: no

Brief summary:
This trial combines dose dense chemotherapy with doxorubicin and cyclophosphamide (AC) followed by standard, every 3 week docetaxel and GW572016 (lapatinib) for neoadjuvant treatment of Her2neu positive stage II/III breast cancer. The purpose of the study was to determine whether lapatinib combined with chemotherapy was safe and resulted in an increase in pathologic complete response rates.

Detailed description:
Lapatinib acts as a dual inhibitor of both epidermal growth factor receptor (EGFR) and ErbB-2 (Her2/neu) tyrosine kinase activity. EGFR and ErbB2 receptors are frequently over-expressed or altered in human cancers including breast cancer. This study plans to determine the antitumor activity of this regimen and its effectiveness preventing tumor growth and spread.

Neoadjuvant chemotherapy which achieves pathologic complete responses (pCR) has been shown to predict improved long-term survival and serves as a surrogate for clinical outcome. By using this primary endpoint we can obtain statistical data with smaller patient numbers and at a lower overall cost. Additionally, we hope to correlate clinical and radiologic outcomes with gene expression data.

Arms:
arm 1: Doxorubicin (Adriamycin) + cyclophosphamide (Cytoxan) with pegfilgrastim or filgrastim growth factor support every 2 weeks for 4 cycles, followed by docetaxel + lapatinib for four 21-day cycles, followed by surgery. Dexamethasone was administered twice-a-day for 3 days, starting 24 hours before the docetaxel infusions. After surgery +/- radiation, participants may receive trastuzumab (Herceptin) for a year.

Interventions: intervention 1: Lapatinib intervention 2: Doxorubicin intervention 3: Cyclophosphamide intervention 4: Docetaxel intervention 5: Pegfilgrastim intervention 6: Filgrastim intervention 7: Dexamethasone intervention 8: Trastuzumab
Intervention descriptions: intervention 1: 1250 mg, tablets, oral daily during treatment with docetaxel (3-week cycles x 4 cycles) intervention 2: 60 mg/m2, intravenously every 2 weeks for 4 cycles. Given as first treatment with cyclophosphamide. intervention 3: 600 mg/m2, intravenously every 2 weeks for 4 cycles. Given as first treatment with doxorubicin. intervention 4: 100 mg/m2, intravenously every 3 weeks for 4 cycles (after treatment cycles of doxorubicin and cyclophosphamide intervention 5: 6 mg, subcutaneously on day 2 of all cytotoxic chemotherapy treatments. intervention 6: 300 or 480 mcg, subcutaneously on days 3 to 10 after cytotoxic chemotherapies. intervention 7: 8 mg, oral taken twice a day for 3 days starting 24 hours before docetaxel intervention 8: Loading dose 8 mg/kg, then 6 mg/kg, intravenously every 3 weeks for 1 year

Protocol document: