Trial Information

Nonrandomized Ph II Study of Multimodality Therapy for Stg IIB, IIIA/B, or Initially Presenting Stg IV Breast Cancer w/ Four Cycles of AC Followed by 12 Weeks of Single Agent Paclitaxel w/ or w/o Herceptin Followed by Local Therapy Followed by Weekly Herceptin or No Additional Therapy

OBJECTIVES:

- Determine the cardiac and other toxicity of paclitaxel when administered with
trastuzumab (Herceptin) after doxorubicin and cyclophosphamide in women with stage IIB,
IIIA, IIIB, IIIC, or previously untreated stage IV breast cancer.

- Determine whether the addition of paclitaxel with or without trastuzumab to
conventional breast cancer adjuvant therapy (doxorubicin and cyclophosphamide) further
decreases tumor size and the number of positive axillary nodes in these patients.

- Determine the 5-year disease-free survival and overall survival of patients treated
with these regimens.

- Determine whether the initial pathologic response in patients receiving neoadjuvant
therapy correlates with the eventual 5-year disease-free survival or overall survival.

- Compare the number of patients eligible for breast-conserving cancer surgery after
treatment with doxorubicin and cyclophosphamide vs paclitaxel and trastuzumab.

- Correlate clinical and radiographic response rate with pathologic response rate in the
primary tumor and axillary lymph nodes and determine which parameter best determines
the pathologic response rate in patients treated with these regimens.

OUTLINE: Patients are assigned to receive either neoadjuvant therapy (HER-2 overexpressing
and nonoverexpressing patients) or adjuvant therapy (HER-2 overexpressing patients only).

- Neoadjuvant therapy: Patients assigned to receive neoadjuvant therapy receive one of
two treatment regimens.

- Regimen I (HER-2 nonoverexpressing patients or HER-2 overexpressing patients who
refuse trastuzumab (Herceptin) therapy): Patients receive doxorubicin IV and
cyclophosphamide IV over 30 minutes and paclitaxel IV over 3 hours on day 1 every
3 weeks for a total of 4 courses. Patients then undergo surgery with or without
adjuvant radiotherapy and/or oral tamoxifen.

- Regimen II (HER-2 overexpressing patients only): Patients receive doxorubicin and
cyclophosphamide as in regimen I. After completion of course 4, patients receive
paclitaxel IV and trastuzumab IV over 90-150 minutes weekly on weeks 13-24.
Patients then undergo surgery with or without adjuvant radiotherapy. Patients then
receive trastuzumab IV over 30 minutes weekly on weeks 29-69 if they did not
receive radiotherapy or on weeks 36-76 if they did receive radiotherapy.

- Adjuvant therapy: Patients who are assigned to receive adjuvant therapy (HER-2
overexpressing patients only) receive doxorubicin IV and cyclophosphamide IV over 30
minutes on day 1 every 3 weeks for a total of 4 courses. After completion of course 4,
patients receive paclitaxel IV and trastuzumab IV over 90 minutes weekly on weeks
13-24. Patients then may undergo radiotherapy followed by trastuzumab IV over 30
minutes weekly on weeks 29-69 if they did not receive radiotherapy or on weeks 36-76 if
they did receive radiotherapy.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then
annually for 5 years.

PROJECTED ACCRUAL: A total of 125 patients (100 in the neoadjuvant group and 25 in the
adjuvant group) will be accrued for this study within 5 years.