A Randomized Phase III Study Exploring the Efficacy of Capecitabine Given Concomitantly or in Sequence to EC-Doc With or Without Trastuzumab as Neoadjuvant Treatment of Primary Breast Cancer
OBJECTIVES:
Primary
- Compare the pathologic complete response rates in women with stage I-III primary breast
cancer treated with neoadjuvant epirubicin hydrochloride, cyclophosphamide, and
docetaxel with versus without capecitabine followed by surgery .
- Compare the pathologic complete response rates in women with HER-2/neu-positive tumors
receiving trastuzumab (Herceptin®) simultaneously with neoadjuvant epirubicin
hydrochloride, cyclophosphamide, and docetaxel to women with HER-2/neu-negative tumors
receiving neoadjuvant chemotherapy only.
Secondary
- Determine the toxicity of these regimens in these patients.
- Determine the disease-free (loco-regional and distant) survival and overall survival of
patients treated with these regimens.
- Determine the disease-free (loco-regional and distant) survival and overall survival of
patients treated with or without trastuzumab.
- Determine the breast conservation rate in patients treated with these regimens.
- Determine the frequency of the use of sentinel node biopsy for selecting patients for
neoadjuvant chemotherapy.
- Compare the frequency of sentinel node biopsies at surgery after neoadjuvant
chemotherapy in each arm.
- Determine the pathologic complete response rates to each regimen in the subgroup of
patients with locally advanced (T4a-d, N0-3, M0) breast cancer.
- Determine the response rate (complete response, partial response, or no change) at
surgery (by imaging methods and by histopathological exam) in patient subgroups
according to their response after four treatments with epirubicin hydrochloride and
cyclophosphamide.
- Determine the intention for the use of neoadjuvant chemotherapy, in terms of freedom
from disease, avoiding mastectomy, improving breast conservation, and gaining
information about efficacy.
OUTLINE: This is a randomized, controlled, open-label, multicenter study. Patients are
stratified according to participating site, clinical response after 4 courses of epirubicin
hydrochloride and cyclophosphamide (complete response vs partial response vs no change),
HER-2/neu-status (negative vs 3+ by immunohistochemistry [IHC] or positive by fluorescence
in situ hybridization [FISH]), estrogen receptor (ER)/progesterone receptor (PR) status (ER
or PR positive vs ER and PR negative), and extent of disease (T4 or N3 vs T1-3 and N0-2).
All patients receive epirubicin hydrochloride IV over 30-60 minutes and cyclophosphamide IV
over 60 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of
disease progression or unacceptable toxicity. Patients are then randomized to 1 of 3
treatment arms.
- Arm I: Patients receive docetaxel IV over 60 minutes on day 1. Treatment repeats every
21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive docetaxel as in arm I. Patients also receive oral capecitabine
twice daily on days 1-14. Treatment with docetaxel and capecitabine repeats every 21
days for 4 courses in the absence of disease progression or unacceptable toxicity.
- Arm III: Patients receive docetaxel as in arm I. Patients then receive oral
capecitabine twice daily on days 1-14. Treatment with capecitabine repeats every 21
days for 4 courses in the absence of disease progression or unacceptable toxicity.
Patients with HER-2/neu-positive tumors also receive trastuzumab (Herceptin®) IV over 90
minutes on day 1 of each course of chemotherapy (during treatment with epirubicin
hydrochloride and cyclophosphamide AND during randomized treatment).
Within 2 weeks after completion of chemotherapy, all patients undergo surgery. Within 2
weeks after surgery, patients with HER-2/neu-positive tumors resume trastuzumab treatment
for up to 1 year.
After completion of study treatment, patients are followed periodically for at least 5
years.
PROJECTED ACCRUAL: A total of 1,500 patients will be accrued for this study.
Interventional
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Pathologic complete response
No
Gunter von Minckwitz, MD
Principal Investigator
German Breast Group
Unspecified
CDR0000455125
NCT00288002
January 2005
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