Trial Information

A Phase III Randomized Neoadjuvant Study of Sequential Epirubicin/Cyclophosphamide and Paclitaxel + - Gemcitabine in Poor Risk Early Breast Cancer

OBJECTIVES:

Primary

- Compare the complete pathological response rate in women with poor-risk early breast
cancer treated with neoadjuvant sequential epirubicin, cyclophosphamide, and paclitaxel
with vs without gemcitabine.

Secondary

- Compare the disease-free and overall survival of patients treated with these regimens.

- Compare the toxicity of these regimens in these patients.

- Compare the effect of these regimens on prognostic factors in these patients.

- Correlate molecular profiles, specific gene mutations, and genomic and gene expression
changes with clinical outcome in these patients.

- Compare the quality of life of patients treated with these regimens.

- Determine the health economics associated with this study.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
estrogen-receptor status (negative vs greater than 10% positive cells), HER-2 status
(positive vs negative), tumor size (30-50 mm vs greater than 50 mm), and clinical
involvement of axillary nodes (yes vs no). Patients are randomized to 1 of 4 treatment arms.

- Neoadjuvant sequential chemotherapy:

- Arm I: Patients receive epirubicin IV and cyclophosphamide IV on day 1. Treatment
repeats every 21 days for 4 courses. Patients then receive paclitaxel IV over 3
hours on day 1. Treatment repeats every 21 days for 4 courses.

- Arm II: Patients receive paclitaxel as in arm I followed by epirubicin and
cyclophosphamide as in arm I.

- Arm III: Patients receive epirubicin and cyclophosphamide as in arm I followed by
paclitaxel as in arm I and gemcitabine IV over 30 minutes on days 1 and 8.
Treatment repeats every 21 days for 4 courses.

- Arm IV: Patients receive paclitaxel as in arm I and gemcitabine as in arm III
followed by epirubicin and cyclophosphamide as in arm I.

- Surgery: After completion of neoadjuvant chemotherapy, patients in all arms undergo
definitive surgery.

Tumor tissue is removed from a subset of patients during serial biopsies. Molecular and
genetic profiling, mutation analysis, and comparative genomic analysis is performed on the
tissue samples.

Quality of life is assessed at baseline, after 4 courses of chemotherapy, after the
completion of chemotherapy, after surgery, and then every 6 months for 2 years.

Patients are followed every 2 months for 2 years and then every 3 months for 3 years.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 800 patients (200 per treatment arm) will be accrued for this
study.