Combination Neoadjuvant Chemotherapy With or Without Apatinib for HER2 Negative Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: The combination of anti-angiogenic targeted therapy with neoadjuvant chemotherapy has been shown to further improve the pathologic response rate for HER2-negative breast cancer patients. Apatinib is a highly potent human vascular endothelial growth factor receptor 2 (VEGFR2) tyrosine kinase inhibitor that has been independently developed in China, and it can exert anti-angiogenic effects by inhibiting VEGFR2. It is unknown whether giving combination neoadjuvant chemotherapy together with apatinib is more effective in treating patients with nonmetastatic HER2-negative breast cancer. PURPOSE: To explore the efficacy and safety of apatinib added to weekly paclitaxel and cisplatin neoadjuvant therapy for HER-2 negative breast cancer patients

Official Title
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Neoadjuvant Apatinib Added to Weekly Paclitaxel and Cisplatin in Patient With Locally Advanced or Early Stage HER2 Negative Breast Cancer (APP) : a Open-label, Randomized, Controlled, Trial

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Apatinib
* Drug: Paclitaxel
* Drug: Cisplatin
* Procedure: Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 70 year-old，Female Patients with histologically confirmed primary invasive breast adenocarcinoma,cT2-4N0-3M0 ECOG 0-1 HER2-negative tumor in biopsy, defined as: Immunohistochemical (IHC) 0-1+ or IHC 2+ confirmed as FISH negative. Adequate organ function Exclusion Criteria: Unwilling to use adequate contraceptive protection during the process of the study and for at least 8 weeks after the last dose of study drug. Pregnant or breastfeeding patients Metastatic or recurrent patients Any evidence of sense or motor nerve disorders Any concurrent malignancy other than breast cancer Uncontrolled hypertension with hypotensive drugs therapy (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg). Patients with grade I or above myocardial ischemia or myocardial infarction or arrhythmia (including QT interval ≥ 440 ms) or cardiac insufficiency Inability to swallow, gastrointestinal resection, chronic diarrhea and obstruction of the intestine, various factors which affect drug use and absorption Coagulation disorders Artery or venous thrombosis occurred within 6 months before the study begins Have received prior treatment with a VEGFR TKI

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: Arm I<br>Apatinib+Paclitaxel+Cisplatin | Drug: Apatinib<br>* Apatinib 250mg, Oral, day 2,3,4,5,6,7, every week<br>Drug: Paclitaxel<br>* Paclitaxel 80mg/m2, Intravenous, day 1, 8, 15, 22, every 28 days for a cycle<br>Drug: Cisplatin<br>* Cisplatin 25mg/m2, Intravenous, day 1, 8, 15, every 28 days for a cycle<br>Procedure: Surgery<br>* Surgery<br>|
| Active Comparator: Arm II<br>Paclitaxel+Cisplatin | Drug: Paclitaxel<br>* Paclitaxel 80mg/m2, Intravenous, day 1, 8, 15, 22, every 28 days for a cycle<br>Drug: Cisplatin<br>* Cisplatin 25mg/m2, Intravenous, day 1, 8, 15, every 28 days for a cycle<br>Procedure: Surgery<br>* Surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Residual cancer burden (RCB 0-I rates） | RCB 0-I rates means RCB 0+I (good response) rates. | Time of surgery | 
| Pathologic Complete Response (pCR) of the Primary Tumor in the Breast | Percentage of patients absent of histologic evidence of invasive tumor cells in the surgical breast specimen. | Time of surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pCR in the Breast and Nodes | Percentage of patients absent of histologic evidence of invasive tumor cells in the surgical breast specimen and axillary lymph nodes. | Time of surgery | 
| Near pCR in the Breast | Percentage of patients with the residual breast lump Less than 10% | Time of surgery | 
| Clinical and imaging response | To determine the response rates of the breast tumor and axillary nodes based on physical examination and imaging tests. (sonography, mammography, or MRI) after treatment | Time of surgery | 
| Number of Participants With Drug Related Treatment Adverse Events | Adverse events that occurred on or after initial treatment that were absent before treatment or worsened during the treatment period relative to the pretreatment state. | an average of 16 weeks | 
| Neo-bioscore | The Neo-Bioscore staging points were determined for each patient based on information from the medical records according to the previously published work（Mittendorf EA, et al. The Neo-Bioscore Update for Staging Breast Cancer Treated With Neoadjuvant Chemotherapy: Incorporation of Prognostic Biologic Factors Into Staging After Treatment. JAMA Oncol. United States; 2016;2:929-36.）. Neo-Bioscore = Clinical stages score + Pathological stages score + Tumor marker score Clinical stage I =0, Clinical stage IIA =0, Clinical stage IIB =1, Clinical stage IIIA =1, Clinical stage IIIB =2, Clinical stage IIIC =2, Pathological stage 0 =0, Pathological stage I =0, Pathological stage IIA =1, Pathological stage IIB =1, Pathological l stage IIIA =1, Pathological stage IIIB =1, Pathological stage IIIC =2, Tumor marker ER negative=1 Tumor marker Grade3=1 Tumor marker ERBB2 negative=1 | Time of surgery | 
| Disease-free Survival (DFS) | DFS is defined as the time period between registration and first event | Measured through 5 years after study enrollment | 
| Distant-disease- free survival (DDFS) | DDFS is defined as the time period between registration and first event | Measured through 5 years after study enrollment | 
| Overall survival (OS) | OS is defined as the time period between registration and first event | Measured through 5 years after study enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Apatinib, Neoadjuvant chemotherapy, Breast cancer