Comparison of TP and TAC Regimens in Neoadjuvant Treatment of TNBC

Study Overview
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Brief Summary
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Previous studies have shown that TNBC is sensitive to DNA crosslinking-related chemotherapeutic drugs such as platinum. However, there is a lack of large sample prospective clinical data to compare the efficacy of TP and EC-T / TEC regimen in the neoadjuvant chemotherapy of TNBC. Besides, the application of anthracycline drugs is limited to a certain extent due to the cardiotoxicity. Based on the above evidence, the researchers hope to explore a more effective and safer new adjuvant therapy for TNBC.

Detailed Description
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In this study, TNBC patients were randomly divided into experimental group and control group, the ratio of experimental group to control group was 1:1. The experimental group received 6 cycles of neoadjuvant chemotherapy (docetaxel 75 mg / m2 day 1 + cisplatin 25 mg / m2 day 1, 2, 3), 21 days as a cycle. The control group was treated with TAC (docetaxel 75mg / M2 + adriamycin 50mg / M2 + cyclophosphamide 500mg / m2) for 6 cycles, 21 days as a cycle. To compare the efficacy and safety of 6*TP (docetaxel + cisplatin) regimen and traditional 6*TAC (docetaxel + doxorubicin + cyclophosphamide) regimen in neoadjuvant chemotherapy of TNBC.

Official Title
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Comparing TP (Docetaxel + Cisplatin) and TAC (Docetaxel + Doxorubicin + Cyclophosphamide) in Neoadjuvant Therapy for Operable Triple Negative Breast Cancer, A Multicenter, Randomized, Phase II Clinical Trial

Conditions
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Triple Negative Breast Cancer

Intervention / Treatment
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* Drug: Docetaxel +doxorubicin+ cyclophosphamide
* Drug: Docetaxel +Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18-70. Clinical T2-T4c, or T1c with axillary LN+. triple negative and invasive breast cancer confirmed by histopathology: Triple negative breast cancer is defined as: negative for ER and PR (IHC nuclear staining < 10%). Her-2 negative (IHC 0,1 + without FISH, or IHC 2 + and FISH without amplification). Clinically evaluable lesions: The presence of lesions that could be evaluated by ultrasound, molybdenum target or magnetic resonance imaging (optional) was within 1 month before randomization. The function examination of organs/bone marrow showed no contraindication within 1 month before chemotherapy. The absolute value of neutrophil count ≥2.0 × 109 / L. The value of hemoglobin ≥100g/L. Platelet count ≥100 × 109/L. Total bilirubin < 1.5 ULN (normal value online). Creatinine < 1.5 × ULN. AST/ALT < 1.5 × ULN. The EF value of echocardiography≥55%. The serum pregnancy test was negative for fertile woman within 14 days before randomization.. KPS score≥80. Informed consent. Exclusion Criteria: Metastatic breast cancer. Before entering the clinical trial, patients had received chemotherapy, endocrine therapy, targeted therapy, radiotherapy and so on. The patient had dual primary malignancies, except for skin cancer, which was treated. Combined with other serious and uncontrollable medical diseases, the researchers judged that the disease had chemotherapy contraindications.

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 |
| --- | --- |
| Placebo Comparator: TAC regimen group<br>The control group was treated with TAC (docetaxel 75mg/m2 + adriamycin 50mg /m2 + cyclophosphamide 500mg/m2) for 6 cycles, 21 days as a cycle. | Drug: Docetaxel +doxorubicin+ cyclophosphamide<br>* The control group was treated with TAC (docetaxel 75 mg / m2 + adriamycin 50 mg / m2 + cyclophosphamide 500 mg / m2) for 6 cycles, 21 days was a cycle.<br>* Other names: TAC regimen group;|
| Experimental: TP regimen group<br>The experimental group was treated with TP (docetaxel 75mg/m2 day 1 + cisplatin 25 mg/m2 day 1,2,3) neoadjuvant chemotherapy for 6 cycles, 21 days as a cycle. | Drug: Docetaxel +Cisplatin<br>* The experimental group was treated with TP (docetaxel 75mg/m2 day 1 + cisplatin 25 mg/m2 day 1,2,3) neoadjuvant chemotherapy for 6 cycles, 21 days as a cycle.<br>* Other names: TP regimen group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The pathological complete remission rate (pCR rate) | It means that there is no invasive cancer (i.e. ypT0/is, ypN0) in the resected specimens (breast + armpit) after operation | Immediately after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event free survival rate (EFS) | Time from randomization to any of the following events: disease progression during neoadjuvant therapy, local or remote recurrence, second primary malignant tumor (breast cancer or other cancers) or death from any cause. | 5 years after surgery | 
| DFS (disease-free survival) | From the date of surgery to the first occurrence of local, regional, contralateral or distant recurrence, as well as death from any cause. | 5 years after surgery | 
| Other defined PCR rates | ypT0ypN0、ypT0/is ypN+、ypT1mic ypN0/+ | Immediately after surgery | 
| Differences in PCR ratio of BRCA mutations and BRCA wild-type patients | Differences in PCR ratio of BRCA mutations and BRCA wild-type patients | Immediately after surgery | 
| Objective response rate | Determine objective response rate based on RECIST v1.1 | before breast cancer surgery | 
| Breast -conserving rate | Breast -conserving rate | up to 24 weeks | 
| Residual cancer burden （RCB） | Evaluation of residual tumor system after neoadjuvant therapy based on breast tumor bed tumors and regional lymph nodes | Immediately after surgery | 
| Number of adverse events and serious adverse events | Evaluate the nature, incidence and severity of chemotherapy adverse events according to CTCAE 4.0 | After each cycle of chemotherapy (21 days as 1 cycle) |