Randomised Phase II Trial of Neoadjuvant Weekly Paclitaxel Plus Carboplatin Compared to Weekly Paclitaxel Alone Followed in Both Arms by Doxorubicin and Cyclophosphamide for Operable or Locally Advanced Basal-like Subtype Breast Cancer Correlating BRCA-1 mRNA and Protein Expression With Carboplatin Response
- To evaluate tumor pathological complete response rate after neoadjuvant paclitaxel with
vs without carboplatin followed by cyclophosphamide and doxorubicin hydrochloride in
women with basal-type subtype primary breast cancer.
- To evaluate the clinical and pathological overall response rate.
- To evaluate safety and toxicity.
- To evaluate disease-free survival and overall survival.
- To correlate low BRCA1 expression (protein and mRNA), p53 mutation, positive CK5/6,
positive CK 14, basal-like gene expression profile, and response to carboplatin-based
OUTLINE: This is a multicenter study. Patients are stratified according to clinical stage
(T2-3 vs T4). Patients are randomized to 1 of 2 treatment arms.
- Arm I (standard therapy): Patients receive paclitaxel IV over 1 hour once weekly in
weeks 1-12. Patients then receive doxorubicin hydrochloride IV and cyclophosphamide IV
on days 1, 8, and 15. Treatment with doxorubicin hydrochloride and cyclophosphamide
repeats every 21 days for 4 courses in the absence of disease progression or
- Arm II (experimental therapy): Patients receive paclitaxel IV over 1 hour and
carboplatin IV over 15 to 20 minutes on days 1, 8, and 15. Treatment with paclitaxel
and carboplatin repeats every 28 days for 4 courses in the absence of disease
progression or unacceptable toxicity. Patients then receive doxorubicin hydrochloride
and cyclophosphamide as in arm I.
All patients will then undergo surgical resection of the tumor.
Patients undergo biopsy for correlative studies. Samples are analyzed for estrogen receptor
and progesterone receptor status, and molecular endpoints (CK 5/6, CK14, p53, BRCA, and
EGFR) by RT-PCR, immunohistochemistry, protein expression, and gene expression profiling.
After completion of study treatment, patients are followed every 3 months for 2 years, every
6 months for 3 years, and then annually thereafter.
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Pathological complete response rate
Pathological response will be assessed by evaluation of surgical specimen after completion of protocol treatment.
Wong Nan Soon, MBBS, MRCP, FAMS
National Cancer Centre, Singapore
Singapore: Health Sciences Authority