Compare the Efficacy and the Safety of Doxorubicin and Cyclophosphamide Followed by Taxotere Versus Doxorubicin and Cyclophosphamide Nanoxel M as Neoadjuvant Chemotherapy in Breast Cancer

Study Overview
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Brief Summary
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Phase III Clinical Trial to Compare the Efficacy and the Safety of AC(Doxorubicin, Cyclophosphamide) Followed by 4 Cycles Taxotere Versus AC(Doxorubicin, Cyclophosphamide) Followed by 4 Cycles Nanoxel M as Neoadjuvant Chemotherapy in Patients With Breast Cancer

Detailed Description
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The purpose of this study is to evaluate efficacy and safety of AC followed by Taxotere versus AC followed by Nanoxel M as neoadjuvant chemotherapy in breast caner patients.

Official Title
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Open-label, Randomized, Active-controlled, Multicenter, Phase III Clinical Trial to Compare the Efficacy and the Safety of AC(Doxorubicin, Cyclophosphamide) Followed by 4 Cycles Taxotere Versus AC(Doxorubicin, Cyclophosphamide) Followed by 4 Cycles Nanoxel M as Neoadjuvant Chemotherapy in Patients With Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Nanoxel M
* Drug: Taxotere
* Drug: Doxorubicin
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who voluntarily decide to participate and give written consent after hearing and understanding detailed explanations of this clinical trial Female adult subjects 19 years of age or older Patients who were diagnosed with primary breast cancer by core biopsy Patients who have been identified as HER2 negative in the tissue obtained through core needle biopsy and have confirmed the positive / negative status of ER (Estrogen receptor) and Progesterone receptor (PR) HER2 positive is defined as IHC 3+ or FISH + Patinets whose TNM stage confirmed by CT or MRI (T2-T3, anyN, M0 or T1-3, N1-3, M0) Patients who show adequate blood, renal, and liver functions at screening as follows <Hematology> ANC ≥ 2.0 X 109/L Platelets ≥ 100 X 109/L Hemoglobin ≥ 10 g/dL (≥ 6.2 mmol/L) <Liver function> Total bilirubin < 1.5 X UNL AST 및 ALT ≤ 2.5 X UNL ALP ≤ 2.5 X UNL <Renal function> Creatinine < 1.5 X UNL (or creatinine clearance ≥ 60ml/min) Patients whose ECOG performance scores are 0-1 Exclusion criteria: Patients who have distant metastasis Patients who have cystitis or urinary obstruction Patients who have history of thromboembolism or coagulation disorder Patients who have Interstitial lung disease ans liver cirrhosis ( > Child-Pugh class B) Patients who have Insulin-Dependent Type II diabete mellitus Hypertensive Patients who have systolic blood pressure ≥ 160mmHg or diastolic blood pressure ≥ 100mmHg Patients who have received chemotherapy prior to participation in this clinical trial or who have received radiation therapy for breast cancer Patients whose medical or mental state judged by the investigator as to be impossible to understand this clinical study and sign the written consent form Patients who have active infection at the screening visit Patients who have history of grade 2 or higher peripheral motor neuropathy or peripheral sensory neuropathy by CTCAE V5.0 Pregnant or lactating women A woman of childbearing age who does not agree to the use of medically acceptable contraceptive methods (blocking, intrauterine contraceptive devices) during the study (However, those who have a record of menopause before definition (defined as amenorrhea for at least one year) or surgical sterilization are excluded from women of childbearing age..) Patients who have a history of malignant tumors except breast cancer within 5 years of screening visit Patients who have heart failure (NYHA class I or higher), arrhythmias requiring treatment, and clinically significant heart valve disease Patients who have transient cerebral ischemic attack (TIA), myocardial infarction, unstable angina, cerebral infarction, cerebral hemorrhage within 6 months prior to screening or a history of angioplasty or coronary artery bypass surgery Patients who have history of anaphylaxis to the main or subcomponents of this ingredient Patients requiring the administration of concomitant contraindications during this clinical trial Patients who are contraindicated in the administration of corticosteroids Patients who have experience of participating in another clinical trial within 3 months to screening (participation is based on the date of final administration of the investigational drug) Other, if the investigator judges that he or she is not suitable to participate

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nanoxel M<br>AC(Doxorubicin, Cyclophosphamide) followed by Nanoxel M | Drug: Nanoxel M<br>* 75 mg/m2, intravenously every 3 weeks for 4 cycles (after treatment cycles of doxorubicin and cyclophosphamide<br>* Other names: polysorbate 80, ethanol free docetaxel;Drug: Doxorubicin<br>* 60 mg/m2, intravenously every 3 weeks for 4 cycles. Given as first treatment with cyclophosphamide<br>Drug: Cyclophosphamide<br>* 600 mg/m2, intravenously every 3 weeks for 4 cycles. Given as first treatment with doxorubicin.<br>|
| Active Comparator: Taxotere<br>AC(Doxorubicin, Cyclophosphamide) followed by Taxotere | Drug: Taxotere<br>* 75 mg/m2, intravenously every 3 weeks for 4 cycles (after treatment cycles of doxorubicin and cyclophosphamide<br>* Other names: docetaxel;Drug: Doxorubicin<br>* 60 mg/m2, intravenously every 3 weeks for 4 cycles. Given as first treatment with cyclophosphamide<br>Drug: Cyclophosphamide<br>* 600 mg/m2, intravenously every 3 weeks for 4 cycles. Given as first treatment with doxorubicin.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological complete response (pCR) rate using the definition of ypT0/Tis ypN0 | H & E staining of tissues obtained from breast and axillary lymph nodes was defined as the absence of invasive cancer, and the proportion of subjects was determined. | at the time of definitive surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of ypT0 Subjects | H & E staining of tissues obtained from breast was defined as the absence of invasive and in situ cancer, and the proportion of subjects was determined. | at the time of definitive surgery | 
| Percentage of ypT0/is Subjects | H & E staining of tissues obtained from breast was defined as the absence of invasive cancer, and the proportion of subjects was determined. | at the time of definitive surgery | 
| Percentage of ypT0 ypN0 Subjects | H & E staining of tissues obtained from breast and axillary lymph nodes was defined as the absence of invasive and in situ cancer, and the proportion of subjects was determined. | at the time of definitive surgery | 
| Response rate | Response rate confirmed by CT or MRI during the study (by RECIST 1.1) | at the time of definitive surgery | 
| Percentage of Subjects with Breast Conservation Surgery | Percentage of Subjects with Breast Conservation Surgery | at the time of definitive surgery | 
| Percentage of subjects by RCB (Residual cancer burden) grade after chemotherapy before surgery | tissue obtained from breat and axillary lymph node were evaluated to determine the proportion of subjects in each grade (RCB 0, RCB-I, RCB-II, RCB III) | at the time of definitive surgery |