A Phase II Study of Chiauranib in Combine With Capecitabine in TNBC

Inclusion Criteria:

1. All patients must have given signed, informed consent prior to registration on study

2. age ≥ 18 years

3. female

4. Histological or cytological evidence of estrogen-receptor negative (ER-),progesterone receptor negative (PgR-) and human epidermal growth factor-2 receptornegative (HER2-) Breast Cancer by local laboratory testing.

5. Patients with locally advanced inoperable or recurrent/metastatic TNBC and hadfailed treatment with anthracyclines and taxanes.

6. At least 1 lesion can be accurately measured, as defined by RECIST1.1

7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

8. Laboratory criteria are as follows:

1. Complete blood count: hemoglobin (Hb) ≥90g/L ; absolute neutrophil count (ANC) ≥1.5×109/L ; platelets ≥90×109/L; 2) Biochemistry test: serum creatinine(cr) <1.5×ULN; total bilirubin<1.5×ULN; alanine aminotransferase(ALT) ,aspartateaminotransferase(AST)≤2.5×ULN; (ALT,AST#5×ULN if liver involved) 3)Coagulation test: International Normalized Ratio (INR) < 1.5

9. Life expectancy of at least 3 months

Exclusion Criteria:

1. Patients have used any anti-cancer therapy, including adiotherapy, chemotherapy,immunotherapy, target therapy, and other anti-tumor treatments within 28 days beforethe first dose

2. Patients received vascular endothelial growth factor(VEGF)/vascular endothelialgrowth factor receptor(VEGFR) inhibitor, like Apatinib, Anlotinib, Fruquintinib,Bevacizumab, etc., or Aurora kinase inhibitors, etc; Patients had treatment ofcapecitabine (except who received the treatment of capecitabine in Neoadjuvant/Adjuvant therapy, and Recurrence occurs after 12 months)

3. Has known allegies to Chiauranib, capecitabine or any of the excipients

4. prior major surgery or trauma within 28 days prior to first dose of study drugand/or presence of any non-healing wound, fracture, or ulcer

5. Treatment with an investigational agent/instrument within 28 days prior to firstdose of study drug

6. Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1

7. Patients with prior invasive malignancies in the past five years with the exceptionof curatively-treated basal cell or squamous cell carcinoma of the skin or cervicalcarcinoma in situ

8. History or clinical evidence of central nervous system (CNS) metastases orleptomeningeal carcinomatosis

9. Have uncontrolled or significant cardiovascular disease, including:

1. Congestive heart failure, unstable angina pectoris, myocardial infarction within 6months prior to study entry; arrhythmia, or Left Ventricular Ejection Fraction (LVEF) < 50% requiring treatment with agents during screening stage 2) primarycardiomyopathy(dilated cardiomyopathy, hypertrophic cardiomyocyte, arrhythmogenicright ventricular cardiomyopathy, restrictive cardiomyopathy, et,al) 3) History ofsignificant QT interval prolongation, or Corrected QT Interval (QTc) > 470 ms priorto study entry 4) Symptomatic coronary heart disease requiring treatment with agents
2. History of hypertension treated by≥2 agents, or the Blood pressure(Bp) ≥140/90mmHg prior to study entry 6) Other condition investigator considered inappropriate

10. CT or MRI of the chest during the screening period shows interstitial lung diseaseor pulmonary fibrosis or lung inflammation that requires treatment, or within 6months before the first dose, history of pneumonia requiring oral or intravenoussteroid treatment

11. Have clinical significant gastrointestinal abnormality that would impair theingestion, transportation or absorption of oral agents, history of gastrointestinalperforation or abdominal fistula, peptic ulcer disease within 6 months prior tofirst dose of study drug

12. Urinary protein ≥ 2+ and quantitative urinary protein ≥ 1g/24 h during the screeningperiod

13. History of active bleeding within the past 2 months, patients with bleedingpotential during the screening period, or receiving anticoagulation therapy

14. Pleural fluid, ascites or pericardial effusion with significant symptoms or requiredtreatment of puncture or drainage during the screening period

15. History of deep venous thrombosis or Pulmonary embolism within the past 6 months

16. Active infection requiring oral or intravenous systemic antimicrobial therapy duringthe screening period

17. Screening for HIV antibody positive

18. Screening test for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive with virus replication, hepatitis C antibody (HCVAb) positive withvirus replication

19. Any mental or cognitive disorder, that would impair the ability to understand theinformed consent document, or the compliance of study

20. Candidates with drug and alcohol abuse

21. Participants of reproductive potential not willing to use adequate contraceptivemeasures for the duration of the study.Pregnant or breastfeeding women

22. Any other condition which is inappropriate for the study in the opinion of theinvestigators