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| ID | Type | Description | Link |
|---|---|---|---|
| SINGAPORE-NCC-0701 |
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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.
OBJECTIVES:
Primary
Secondary
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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1 (Standard Arm) | Other | Arm 1 (Standard Arm) Preoperative (primary/ neoadjuvant) intravenous weekly paclitaxel 80 mg/m2 for 12 weeks followed by doxorubicin 60 mg/m2 in combination with cyclophosphamide 600 mg/m2 every 21 days for 4 cycles. |
|
| Arm 2 (Experimental Arm) | Experimental | Arm 2 (Experimental Arm) Preoperative intravenous weekly paclitaxel 80 mg/m2 in combination with carboplatin AUC 2 on D1, D8 and D15 every 28 days for 4 cycles followed by doxorubicin 60 mg/m2 in combination with cyclophosphamide 600 mg/m2 every 21 days for 4 cycles. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| carboplatin | Drug |
| ||
| cyclophosphamide |
| Measure | Description | Time Frame |
|---|---|---|
| Pathological complete response rate | Pathological response will be assessed by evaluation of surgical specimen after completion of protocol treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical and pathological overall response rates | Clinical response: Serial 4 weekly clinical examination; Mammography, breast ultrasound: Baseline, 3 weeks after treatment protocol or documented clinical progression. Pathological response: Evaluation of surgical specimen after protocol treatment. | |
| Overall and disease-free survival |
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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:
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:
PATIENT CHARACTERISTICS:
Inclusion criteria:
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:
Prior malignancies except for basal cell carcinoma of the skin or curatively treated carcinoma in situ of the cervix
PRIOR CONCURRENT THERAPY:
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| Name | Affiliation | Role |
|---|---|---|
| Wong Nan Soon, MBBS, MRCP, FAMS | National Cancer Centre, Singapore | Principal Investigator |
| Ann Lee Siew Gek | National Cancer Centre, Singapore | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Cancer Centre - Singapore | Singapore | 169610 | Singapore | |||
| KK Women's and Children Hospital |
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|
| doxorubicin hydrochloride | Drug |
|
| paclitaxel | Drug |
|
| Clinical response: Serial 4 weekly clinical examination; Mammography, breast ultrasound: Baseline, 3 weeks after treatment protocol or documented clinical progression. Pathological response: Evaluation of surgical specimen after protocol treatment. |
| Incidence of each toxicity item | Clinical response: Serial 4 weekly clinical examination; Mammography, breast ultrasound: Baseline, 3 weeks after treatment protocol or documented clinical progression. Pathological response: Evaluation of surgical specimen after protocol treatment. |
| 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 | Clinical response: Serial 4 weekly clinical examination; Mammography, breast ultrasound: Baseline, 3 weeks after treatment protocol or documented clinical progression. Pathological response: Evaluation of surgical specimen after protocol treatment. |
| Singapore |
| Singapore |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| D016190 | Carboplatin |
| D003520 | Cyclophosphamide |
| D004317 | Doxorubicin |
| D017239 | Paclitaxel |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D004224 | Diterpenes |
| D013729 | Terpenes |
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