A Phase II Study of Neoadjuvant Chemotherapy With and Without Trastuzumab in Patients With Breast Cancer
I. To evaluate the toxicities and tolerability of a neoadjuvant dose-dense regimen
cyclophosphamide and paclitaxel with or without trastuzumab/radiation therapy (as clinically
indicated) in patients with newly diagnosed stage T1cN0 and II-III breast cancer; followed
by maintenance trastuzumab in human epidermal growth factor receptor 2 (HER2) positive OR
Adriamycin (doxorubicin hydrochloride) followed by radiation therapy (RT) in stage II-III
triple negative HER2 (-), estrogen receptor (ER) (-), progesterone receptor (PR) (-) stage
T1cN0 and II-III breast cancer patients.
II. To determine the pathological complete response rate (pCR) of this treatment regimen.
III. To identify possible gene expression profile signatures from whole genome array
analysis that correlate with clinical response/resistance to chemotherapy as measured by
pathologic complete response rate (pCR).
NEOADJUVANT THERAPY: Patients receive paclitaxel intravenously (IV) over 3 hours and
cyclophosphamide IV over 1 hour on day 1. Patients with HER2-positive cancer also receive
trastuzumab IV over 30 minutes on day 1. Treatment repeats every 14 days for up to 6 courses
in the absence of disease progression or unacceptable toxicity. Patients without metastasis
undergo mastectomy or breast conserving surgery 4-8 weeks later.
HER2-POSITIVE PATIENTS: Patients receive standard radiation therapy. Patients also receive
trastuzumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 13
courses in the absence of disease progression or unacceptable toxicity.
ER/PR POSITIVE PATIENTS: Patients receive standard adjuvant hormonal or endocrine therapy.
STAGE T1cN0 TRIPLE NEGATIVE PATIENTS: Patients receive standard radiation therapy.
STAGE II-III TRIPLE NEGATIVE PATIENTS: Patients receive doxorubicin hydrochloride IV over 15
minutes on day 1. Treatment repeats every 14 days for up to 4 courses in the absence of
disease progression or unacceptable toxicity. Patients also receive standard radiation
After completion of study treatment, patients are followed up every 3 months for 2 years.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
pCR, determined from the surgical specimen and is defined as the absence of invasive carcinoma in both the breast and axilla at microscopic examination of the resection specimen, regardless of the presence of carcinoma in situ
The pCR rates and exact one-sided 80% confidence intervals will be calculated. The primary analysis is based on the full analysis set (all treated patients). The pCR rates will be summarized overall and for HER+ and HER- subsets.
University of Nebraska
United States: Institutional Review Board
|University of Nebraska Medical Center||Omaha, Nebraska 68198-3330|
|Saint Francis Medical Center||Grand Island, Nebraska 68802|