oral etoposide combined with anlotinib in advanced triple negative breast cancer

Conditions: Triple Negative Breast Cancer

Summary: the hypothesis of this study is to discover if the oral etoposide plus anlotinib can shrink or slow the growth of pretreated advanced tnbc. it is a single-arm, multicenter phase ii clinical study of oral etoposide combined with antinib in the treatment of recurrent or metastatic triple-negative breast cancer

it is a single-arm, multicenter phase ii clinical study of oral etoposide combined with antinib in the treatment of recurrent or metastatic triple-negative breast cancer. the hypothesis of this study is to discover if the oral etoposide plus anlotinib can shrink or slow the growth of pretreated advanced tnbc.

Eligibility criteria:
inclusion criteria: * age between 18 and 75 year-old women; tnbc * ecog score: 0-1, expected survival time ≥ 3months; * pathologically or cytologically confirmed breast cancer; * anthracycline- / taxane- pretreated (adjuvant, neoadjuvant) breast cancer patients who have failed from 1-3 standard chemotherapies after recurrence and metastasis; * according to recist 1.1, exist at least ≥1 measurable lesion(ct \>1cm，other examination \>2cm); * the patients have enough organ function. the laboratory test indexes must comply with the following requirements: * blood routine: neutrophil≥1.5g/l, platelet count ≥80g/l, hemoglobin ≥90g/l * liver function: serum bilirubin ≤ 1.5 times the upper limit of normal value; alt and ast≤2.5 times the upper limit of normal value; alt and ast≤5 times the upper limit of normal value when liver metastasis * renal function: serum creatinine ≤ 1.0times the upper limit of normal value, creatinine clearance \>50ml/min（cockcroft-gault formula) * women of child-bearing age should be carried out pregnancy test (serum or urine) within 7 days before recruit, the results should be negative; and are willing to adopt the appropriate methods of contraception during the trial and 8 weeks after last administration； * can swallow oral drugs; * the patients have good compliance to the therapy and follow-up to be scheduled and are able to understand the study protocol and sign the informed consent form. exclusion criteria: * the patients in pregnancy or lactation growth period and did not take effective contraception; * the patients who received ≥4 chemotherapies after recurrence and metastasis; involved in other clinical trials four weeks prior to the start of the study; * the patients with a variety of factors that affect the oral administration and absorption of drugs; * prior treatment with etoposide or antiangiogenic tki (subjects with prior use of antiangiogenic macromolecules such as bevacizumab are allowed to be enrolled); * the patients have uncontrollable mental illness； * serous cavity effusion (such as pleural effusion and ascites) with clinical symptoms requiring clinical intervention or stable time less than 4 weeks; * the patients who had serious adverse effect to oral etoposide or were allergic to etoposide. * the patients who have only bone metastasis without other measurable lesion; * the patients experience severe cardiovascular diseases; * the patients experience severe upper gastrointestinal ulcer or malabsorption syndrome. * abnormal bone marrow functions(neutrophil\<1.5g/l, platelet count \<75g/l, hemoglobin \<90g/l); * abnormal renal function(serum creatinine \> 1.5 times the upper limit of normal value); * abnormal liver function(serum bilirubin ≤ 1.5 times the upper limit of normal value); * the patients have uncontrollable brain metastasis; * active or uncontrolled infection requiring systematic treatment (except simple urinary tract infection or upper respiratory tract infection) during the 2 weeks or 2 weeks prior to enrollment; * previous or concurrent history of other malignant tumors.except for the cured skin basal cell carcinoma and cervical carcinoma in situ; * the patients do have good compliance to the therapy.