Addition of Cisplatin to Adjuvant Chemotherapy for Early Stage Breast Cancer in High-Risk Women

Study Overview
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Brief Summary
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The investigators hypotheses that paclitaxel combined with cisplatin in a weekly-based regimen as adjuvant chemotherapy is more effective for high risk, HER2 negative breast cancer .

Detailed Description
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In this trial, patients will be randomly assigned in a 2:1 ratio to receive cisplatin-based adjuvant chemotherapy and to standard adjuvant chemotherapy.

Official Title
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Phase 3 Study of Weekly Paclitaxel in Combination With Cisplatin as Adjuvant Chemotherapy for Early Stage Human Epidermal Growth Factor Receptor-2 (HER2) Negative Breast Cancer in High-risk Women

Conditions
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Tubular Breast Cancer, Mucinous Breast Cancer, Invasive Duct Carcinoma of Breast

Intervention / Treatment
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* Drug: Paclitaxel, Cisplatin
* Drug: EC to docetaxel or paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged ≥18 years and ≤70 years Have accepted surgical treatment, histologically confirmed early breast cancer, the pathological types of invasive carcinoma Not received treatment for breast cancer before operation Triple-negative breast cancer confirmed by pathology, or pathology confirmed as the HR positive breast cancer at the same time meet the following conditions: axillary lymph node positive breast cancer, tumor size≥2 cm and Ki - 67 >20% or tumor size ≥2 cm and grade III or tumor size ≥2cm and aged <35 years HER2 negative: immunohistochemistry HER2 (1 +) or HER2 (0), or fluorescence in situ hybridization (FISH): not amplified Performance status (PS) 0-1 Adequate bone marrow function:WBC≥4.0×109/L, Absolute neutrophil count（ANC）≥1.5×109/L, Platelets（PLT）≥100×109/L, Hemoglobin（Hb）≥90g/L;aspartate aminotransferase(AST),Alanine aminotransferase (ALT)≤1.5 upper normal limit , creatinine≤1.5 upper normal limit, bilirubin≤1.5 upper normal limit No obvious main organs dysfunction Exclusion Criteria: metastatic breast cancer Patient is pregnant or breast feeding Any evidence of sense or motor nerve disorders Bilateral Primary Breast Cancer (DCIS in one side not included) Patients with medical conditions taht indicate intolerant to adjuvant chemotherapy, including uncontrolled cardiovascular disease, severe infection Have received chemotherapy because of any malignancy other than breast cancer Known severe hypersensitivity to any drugs in this study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: paclitaxel and cisplatin<br>Drug: paclitaxel, cisplatin, epirubicin and cyclophosphamide Patients will be administered paclitaxel (80 mg/m² i.v. given weekly on day 1 q day 8 for 12 weeks) and cisplatin (25 mg/m² weekly on day 1 ,8,and 15 q day 28 for 3 cycles) followed by epirubicin and cyclophosphamide (EC) (epirubicin 90mg/m² i.v.d1, cyclophosphamide 600mg/m² i.v.d1) for 4 cycles. | Drug: Paclitaxel, Cisplatin<br>* weekly paclitaxel and cisplatin<br>* Other names: Taxol;|
| Active Comparator: epirubicin and cyclophosphamide<br>Drug：epirubicin, cyclophosphamide, paclitaxel and docetaxel Investigators will declare one of the following regimens: Patients with hormone receptor (HR) positive breast cancer wil be administered epirubicin (90mg/m² i.v.d1 q21d) and cyclophosphamide (600mg/m² i.v.d1 q21d) for 4 cycles followed by docetaxel (75mg/m² i.v.d1 q21d) for 4 cycles. Patients with triple-negative breast cancer will be administered epirubicin (90mg/m² i.v.d1 q21d) and cyclophosphamide (600mg/m² i.v.d1 q21d) for 4 cycles followed by weekly paclitaxel (80 mg/m² i.v.d1) for 12 weeks or docetaxel (75mg/m² i.v.d1 q21d) for 4 cycles. | Drug: EC to docetaxel or paclitaxel<br>* Standard adjuvant chemotherapy recommended by guideline<br>* Other names: Taxol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Disease-Free Survival (DFS) Events | DFS is defined as the time period between registration and first event | up to 5 year follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Overall Survival (OS) Events | OS is defined as the time period between registration and first event | up to 5 year follow up | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v3.0. | Descriptive statistics for the treatment will be given on the number of patients whose treatment had to be reduced, delayed or permanently stopped | 5 months during adjuvant therapy |