Neoadjuvant Treatment of Docetaxel, Anthracycline and Cyclophosphamide (TAC) Versus Docetaxel and Cyclophosphamide (TC) in Triple-Negative or Her2 Positive Breast Cancer

Study Overview
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Brief Summary
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The purpose of this study is to compare the pathological complete response (pCR) rate in triple-negative or Her2 positive breast cancer patients treated with neoadjuvant docetaxel, anthracycline and cyclophosphamide (TAC) or docetaxel and cyclophosphamide (TC) regimen.

Detailed Description
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Breast cancer is the leading cause of cancer in women in China. Neoadjuvant chemotherapy for treatment of locally advanced breast cancer has become a standard therapy. Results from neoadjuvant trials have shown that pathological complete response (pCR) is an independent predictor of outcome. Docetaxel was introduced into clinical practice in the early 1990s and has demonstrated good activity in the adjuvant and metastatic settings. Both TC and TAC are effective regimens in the adjuvant setting. The most optimal regimen in the neoadjuvant treatment is however unknown. This is especially true in triple-negative or HER2 positive breast cancer. This study will evaluate the pCR rate of TAC and TC as neoadjuvant treatment for triple-negative or HER2 positive breast cancer.

Official Title
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A Multi-Center, Randomized Study of Docetaxel, Anthracycline and Cyclophosphamide (TAC) Versus Docetaxel and Cyclophosphamide (TC) in Neoadjuvant Treatment of Triple-Negative or Her2 Positive Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Docetaxel, Anthracycline (Doxorubicin or Epirubicin), Cyclophosphamide
* Drug: Docetaxel, cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged ≥ 18 years and < 70 years Karnofsky performance status (KPS) ≥ 70 At least one measurable disease according to the RECIST. histologically confirmed invasive breast cancer (excluding inflammatory breast cancer), T2N1 or locally advanced breast cancer (T3-4N0-3 or T0-4N2-3) Biopsy specimens are available for ER, PgR and Her2 detection, patients should be with triple negative or Her2 positive breast cancer, Her2 positivity is defined as FISH/CISH Her2 positive or IHC Her2 3+, Triple-negative disease defined as negativity for ER, PgR and Her2 Adequate bone marrow function: Neutrophil ≥ 1.5*109/L; Hb ≥ 100g/L; PLT ≥ 100*109/L An estimated life expectancy of at least 12 months Willing to take biopsy before neoadjuvant chemotherapy and patients must be accessible for treatment and follow-up Women with potential child-bearing must have a negative pregnancy test (urine or serum) within 7 days of drug administration and agree to use an acceptable method of birth control to avoid pregnancy for the duration of the study Written informed consent according to the GCP Exclusion Criteria: Prior systemic or loco-regional treatment of breast cancer, including chemotherapy Metastatic breast cancer With a history of malignant tumor except uterine cervix cancer in situ or skin basal cell carcinoma Patients with medical conditions that indicate intolerant to neoadjuvant therapy and related treatment, including uncontrolled pulmonary disease, diabetes mellitis, severe infection, active peptic ulcer, coagulation disorder, connective tissue disease or myelo-suppressive disease inadequate liver function (bilirubin > 1.0 times upper normal limit [UNL] and ALT and/or AST> 1.5 UNL associated with alkaline phosphatase > 2.5 UNL; inadequate renal function (creatinine > 1.0 times UNL and in case of limit value, Creatinine clearance < 60 ml/min) Contraindication for using dexamethasone History of congestive heart failure, uncontrolled or symptomatic angina pectoris, arrhythmia or myocardial infarction; poorly controlled hypertension (systolic BP > 180 mmHg or diastolic BP > 100 mmHg) Has peripheral neuropathy ≥ grade 1 Patient is pregnant or breast feeding Known severe hypersensitivity to any drugs in this study Treatment with any investigational drugs within 30 days before the beginning of study treatment

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: TAC Arm<br>six cycles of neoadjuvant Docetaxel, Anthracycline and Cyclophosphamide | Drug: Docetaxel, Anthracycline (Doxorubicin or Epirubicin), Cyclophosphamide<br>* Docetaxel 75mg/m2, doxorubicin 50mg/m2 or epirubicin 60mg/m2, cyclophosphamide 500mg/m2 every 3 weeks for six cycles<br>|
| Experimental: TC Arm<br>six cycles of neoadjuvant Docetaxel and Cyclophosphamide | Drug: Docetaxel, cyclophosphamide<br>* Docetaxel 75mg/m2, cyclophosphamide 600mg/m2 every 3 weeks for six cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pathological complete remission (pCR) rate |  | after 6 cycles of neoadjuvant therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease free survival (DFS) and overall survival (OS) |  | 5-year | 
| clinical response rate |  | after 6 cycles of neoadjuvant therapy | 
| safety profile |  | during neoadjuvant therapy | 
| breast conservation therapy (BCT) rate |  | after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Neoplasms, Neoadjuvant, Chemotherapy, Docetaxel, Cyclophosphamide, Anthracycline