Trial Information

Pilot Trial of Paclitaxel-Herceptin Adjuvant Therapy for Early Stage Breast Cancer

OBJECTIVES:

I. Evaluate the safety of paclitaxel plus trastuzumab (Herceptin) followed by adjuvant
chemotherapy in women with node positive stage II or IIIa breast cancer with HER2
overexpression.

II. Evaluate the safety of long term trastuzumab (Herceptin) in this patient population.

OUTLINE: This is a randomized study. Patients are stratified according to radiotherapy (none
planned vs planned to breast or chest wall). Patients are randomized to one of two treatment
arms.

ARM I: Patients receive paclitaxel IV over 3 hours immediately followed by trastuzumab
(Herceptin) IV over 30-90 minutes on day 1. Paclitaxel repeats every 3 weeks for 4 courses
and trastuzumab (Herceptin) repeats weekly for 10 courses. At 3 weeks following paclitaxel
and trastuzumab (Herceptin), patients receive doxorubicin IV and cyclophosphamide IV over 1
hour every 3 weeks for 4 courses. Following chemotherapy, estrogen receptor (ER) positive
and/or progesterone receptor (PR) positive patients receive oral tamoxifen twice daily for 5
years.

ARM II: Patients receive same therapy as in Arm I, except for additional trastuzumab
(Herceptin) IV weekly beginning within 3 weeks following completion of chemotherapy and
local therapy and continuing for 1 year. ER and/or PR positive patients receive tamoxifen as
in Arm I but may be concurrent with trastuzumab (Herceptin). Following completion of
doxorubicin and cyclophosphamide, post lumpectomy and post mastectomy patients may receive
local radiotherapy daily for 5-6 weeks. Treatment continues in the absence of disease
progression or unacceptable toxicity.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then
annually thereafter.

PROJECTED ACCRUAL: A total of 200 patients (100 per treatment arm) will be accrued for this
study within 1 year.