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
18 Years
N/A
Female
Breast Cancer
Trial Information
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
OBJECTIVES:
Primary
- 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.
Secondary
- 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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed invasive basal-type breast cancer meeting the following
criteria:
- Newly diagnosed disease
- Locally advanced or operable primary disease > 2 cm, without evidence of
metastatic disease
- Clinical T2 (> 2 cm), T3 (> 5 cm), or T4 primary tumors with or without clinical
lymph node involvement (N0-3)
- T4 tumors are defined by any of the following:
- Skin ulceration
- Satellite nodules
- Peau d' orange (skin edema)
- Chest wall invasion
- Inflammatory breast cancer
- Her-2/neu 0-1+ by IHC (or negative by fluorescent in situ hybridization if Her-2 2+
by immunohistochemistry)
- No metastatic disease
- Hormone receptor status:
- Estrogen and progesterone receptor-negative disease
PATIENT CHARACTERISTICS:
Inclusion criteria:
- Female
- Menopausal status not specified
- ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%
- Life expectancy > 10 years
- Leukocytes ≥ 3,000/μL
- Absolute neutrophil count ≥ 1,500/μL
- Platelets ≥ 100,000/μL
- Total bilirubin normal
- AST and ALT ≤ 2.5 times upper limit of normal
- Creatinine normal OR creatinine clearance ≥ 60 mL/min
- Not pregnant or nursing
- Fertile patients must use effective contraception
- Cardiac ejection fraction ≥ 50% as assessed by MUGA scan or 2D echocardiogram
Exclusion criteria:
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to paclitaxel, carboplatin, or other agents used in the study
- Pre-existing peripheral neuropathy
- Uncontrolled intercurrent illness including, but not limited to, any of the
following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness or social situations that would limit compliance with study
requirements
- Prior malignancies except for basal cell carcinoma of the skin or curatively treated
carcinoma in situ of the cervix
PRIOR CONCURRENT THERAPY:
- No prior chemotherapy or radiotherapy
- No HIV-positive patients receiving combination antiretroviral therapy
- No concurrent primary growth factor prophylaxis
- No other concurrent investigational agents
- No other concurrent chemotherapy, immunotherapy, hormonal cancer therapy, surgery for
cancer, or experimental medications
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Pathological complete response rate
Outcome Time Frame:
Pathological response will be assessed by evaluation of surgical specimen after completion of protocol treatment.
Safety Issue:
No
Principal Investigator
Wong Nan Soon, MBBS, MRCP, FAMS
Investigator Role:
Principal Investigator
Investigator Affiliation:
National Cancer Centre, Singapore
Authority:
Singapore: Health Sciences Authority
Study ID:
CDR0000579522
NCT ID:
NCT00589238
Start Date:
January 2008
Completion Date:
Related Keywords:
- Breast Cancer
- stage II breast cancer
- stage IIIA breast cancer
- stage IIIB breast cancer
- stage IIIC breast cancer
- Breast Neoplasms
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