A Study of Weekly Doxorubicin and Daily Oral Cyclophosphamide Plus G-CSF Followed by Weekly Paclitaxel as Neoadjuvant Therapy for Resectable, Hormone Receptor Negative or Hormone Receptor Positive, HER-2/Neu Positive Breast Cancer Followed by a Novel Regimen of Capecitabine, Methotrexate and Vinorelbine for Patients Who Do Not Have Either a Macroscopic or Microscopic Pathologic Complete Response, a Phase II Study
I. To assess the pathologic response rate in patients with operable breast cancer treated
with a two part, neoadjuvant regimen consisting of weekly doxorubicin (doxorubicin
hydrochloride) and daily oral cyclophosphamide given with G-CSF (filgrastim) support for 12
weeks followed weekly paclitaxel for 12 weeks.
I. To assess the clinical response rate in patients with surgically resectable breast cancer
treated with weekly doxorubicin and daily oral cyclophosphamide given with G-CSF support for
II. To assess the clinical response rate in patients with surgically resectable breast
cancer treated with weekly paclitaxel for 12 weeks.
III. To assess the relapse rate, overall and disease-free survival in patients with operable
breast cancer treated with neoadjuvant chemotherapy consisting of weekly doxorubicin and
daily oral cyclophosphamide given with G-CSF support for 12 weeks followed weekly paclitaxel
for 12 weeks and adjuvant chemotherapy with Xeloda (capecitabine), Methotrexate and
Navelbine (vinorelbine tartrate) (XMN).
IV. To assess the toxicity associated with these regimens. V. To assess whether the
phenotype of breast cancer changes with treatment. VI. To assess whether phenotypic changes
in breast tumors predict outcome.
PART I: Patients receive doxorubicin hydrochloride intravenously (IV) on day 1 of each week,
cyclophosphamide orally (PO) once daily (QD), and filgrastim subcutaneously (SC) QD on days
2-7 of each week. Treatment continues for 12 weeks in the absence of disease progression or
PART II: Patients* receive paclitaxel IV over 1 hour on day 1 of each week. Treatment
continues for 12 weeks in the absence of disease progression or unacceptable toxicity.
Patients then undergo definitive surgical resection by partial mastectomy (lumpectomy) or
mastectomy after completion of neoadjuvant chemotherapy.
PART III: Patients** unable to achieve complete pathologic response (pCR) or disease that
has been down-staged to =< 1 cm with no positive nodes following surgery receive
capecitabine PO twice daily (BID) on days 1-14, methotrexate IV on days 1, 8 and 15, and
vinorelbine tartrate IV over 6-10 minutes on days 1, 8, and 15. Treatment repeats every 3
weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
NOTE: *Patients with HER2/neu-positive disease also receive trastuzumab IV over 30-90
minutes once weekly or every 3 weeks for 1 year beginning in Part II.
NOTE: **Patients with hormone receptor-positive disease also receive tamoxifen PO QD for 5
years (premenopausal) OR letozole PO QD or tamoxifen PO QD for 5 years (postmenopausal)
beginning in Part III.
After completion of study treatment, patients are followed up every 3 months for 3 years,
every 6 months for 2 years, and then annually thereafter.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Combined rate of microscopic pCR and macroscopic pathologic complete response (mCR)
Microscopic pCR: No evidence of microscopic invasive tumor at the primary site or in the regional lymph nodes at the time of definitive surgical resection. mCR: The examining pathologist cannot identify gross residual tumor mass in the surgical specimen. This differs from a pCR where the specimen must also be negative for invasive tumor by microscopy. For this study, we are using a definition of mCR that will make the trial more translatable to other institutions. For this study, mCR will be defined as no focus of invasive cancer >= 1 cm.
At the end of part II, before surgical resection
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
United States: Food and Drug Administration
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium||Seattle, Washington 98109|