Phase II Study of Dose-Dense Doxorubicin and Cyclophosphamide (AC) Followed by Weekly Paclitaxel With Trastuzumab and Lapatinib in HER2/NEU-Overexpressed/Amplified Breast Cancer: Feasibility
- Determine the feasibility of dose-dense doxorubicin hydrochloride and cyclophosphamide
followed by paclitaxel, trastuzumab (Herceptin®), and lapatinib ditosylate in patients
with HER2/neu-overexpressed/amplified breast cancer.
- Assess the toxicity of this regimen in these patients.
- Determine the time to recurrence in patients treated with this regimen.
- Determine the overall survival of patients treated with this regimen.
- Explore the use of serial troponin I (cTnI) and C-reactive protein (CRP) as a predictor
of cardiac toxicity of this regimen in these patients.
OUTLINE: This is a multicenter study. Patients may receive therapy as neoadjuvant or
adjuvant administration. Chemotherapy must be completed before breast surgery in case of
neoadjuvant therapy. Adjuvant therapy must begin within 84 days after breast surgery.
- Chemotherapy: Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on
day 1. Treatment repeats every 2 weeks for 4 courses. Patients then receive paclitaxel
IV once weekly for 12 weeks.
- Trastuzumab (Herceptin®) and lapatinib ditosylate: Beginning concurrently with
paclitaxel, patients receive trastuzumab IV over 30-90 minutes once weekly for 12 weeks
and then once every 3 weeks, beginning at least 1 week after completion of paclitaxel,
for a total of 52 weeks. Patients also receive oral lapatinib ditosylate once daily,
beginning concurrently with paclitaxel, for a total of 52 weeks.
Treatment continues in the absence of disease progression or unacceptable toxicity.
Blood samples are collected at baseline, every 2 weeks during chemotherapy, and at 6, 9, and
18 months. Samples are examined for serial troponin and C-reactive protein.
After completion of study treatment, patients are followed every 3-6 months for 3 years,
every 6 months for 2 years, and then annually thereafter.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Chau T. Dang, MD
Memorial Sloan-Kettering Cancer Center
United States: Institutional Review Board
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|
|Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute||Boston, Massachusetts 02115|