Paclitaxel, Doxorubicin, and Cyclophosphamide With Or Without Carboplatin in Treating Women With Locally Advanced Breast Cancer That Can Be Removed by Surgery
Recruitment status was Recruiting
RATIONALE: Drugs used in chemotherapy, such as paclitaxel, doxorubicin, cyclophosphamide, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether combination chemotherapy is more effective with or without carboplatin in treating breast cancer.
PURPOSE: This randomized phase II trial is studying giving paclitaxel together with doxorubicin and cyclophosphamide to see how well it works compared to giving paclitaxel together with doxorubicin, cyclophosphamide, and carboplatin in treating women with locally advanced breast cancer that can be removed by surgery.
Drug: doxorubicin hydrochloride
Genetic: microarray analysis
Genetic: protein expression analysis
Genetic: reverse transcriptase-polymerase chain reaction
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Procedure: conventional surgery
Procedure: neoadjuvant therapy
|Study Design:||Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- Pathological complete response rate [ Designated as safety issue: No ]
- Clinical and pathological overall response rates [ Designated as safety issue: No ]
- Overall and disease-free survival [ Designated as safety issue: No ]
- Incidence of each toxicity item [ Designated as safety issue: Yes ]
- Correlation between low BRCA1 expression (protein and mRNA), p53 mutation, positive CK5/6, positive CK14, basal like gene expression profile, and response to carboplatin based treatment [ Designated as safety issue: No ]
|Study Start Date:||January 2008|
|Estimated Primary Completion Date:||January 2011 (Final data collection date for primary outcome measure)|
- 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 treatment.
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 unacceptable toxicity.
- 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.
|National Cancer Centre - Singapore||Recruiting|
|Singapore, Singapore, 169610|
|Contact: Wong Nan Soon, MBBS, MRCP, FAMS 65-6-436-8088|
|Principal Investigator:||Wong Nan Soon, MBBS, MRCP, FAMS||National Cancer Centre, Singapore|
|Principal Investigator:||Ann Lee Siew Gek||National Cancer Centre, Singapore|