Breast Cancer
Conditions
Keywords
Apatinib, Neoadjuvant chemotherapy, Breast cancer
Brief summary
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
Interventions
DRUGApatinib
Apatinib 250mg, Oral, day 2,3,4,5,6,7, every week
DRUGPaclitaxel
Paclitaxel 80mg/m2, Intravenous, day 1, 8, 15, 22, every 28 days for a cycle
DRUGCisplatin
Cisplatin 25mg/m2, Intravenous, day 1, 8, 15, every 28 days for a cycle
PROCEDURESurgery
Surgery
Sponsors
RenJi Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. 18\ 70 year-old，Female 2. Patients with histologically confirmed primary invasive breast adenocarcinoma,cT2-4N0-3M0 3. ECOG 0-1 4. HER2-negative tumor in biopsy, defined as: Immunohistochemical (IHC) 0-1+ or IHC 2+ confirmed as FISH negative. 5. Adequate organ function
Exclusion criteria
1. 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. 2. Pregnant or breastfeeding patients 3. Metastatic or recurrent patients 4. Any evidence of sense or motor nerve disorders 5. Any concurrent malignancy other than breast cancer 6. 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 7. Inability to swallow, gastrointestinal resection, chronic diarrhea and obstruction of the intestine, various factors which affect drug use and absorption 8. Coagulation disorders 9. Artery or venous thrombosis occurred within 6 months before the study begins 10. Have received prior treatment with a VEGFR TKI
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Residual cancer burden (RCB 0-I rates） | Time of surgery | RCB 0-I rates means RCB 0+I (good response) rates. |
| Pathologic Complete Response (pCR) of the Primary Tumor in the Breast | Time of surgery | Percentage of patients absent of histologic evidence of invasive tumor cells in the surgical breast specimen. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical and imaging response | Time of surgery | 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 |
| Number of Participants With Drug Related Treatment Adverse Events | an average of 16 weeks | 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. |
| Neo-bioscore | Time of surgery | 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 |
| pCR in the Breast and Nodes | Time of surgery | Percentage of patients absent of histologic evidence of invasive tumor cells in the surgical breast specimen and axillary lymph nodes. |
| Distant-disease- free survival (DDFS) | Measured through 5 years after study enrollment | DDFS is defined as the time period between registration and first event |
| Overall survival (OS) | Measured through 5 years after study enrollment | OS is defined as the time period between registration and first event |
| Disease-free Survival (DFS) | Measured through 5 years after study enrollment | DFS is defined as the time period between registration and first event |
| Near pCR in the Breast | Time of surgery | Percentage of patients with the residual breast lump Less than 10% |
Countries
China
Outcome results
None listed