Oral Etoposide Combined With Anlotinib in Advanced Triple Negative Breast Cancer

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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Oral Etoposide Combined With Anlotinib in Advanced Triple Negative Breast Cancer

Conditions
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Triple Negative Breast Cancer

Intervention / Treatment
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* Drug: oral etoposide + anlotinib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: oral Etoposide+Anlotinib<br>anlotinib 12mg qd, d1-14，21days/cycle oral etoposide 75mg qd，d1-10，21days/cycle | Drug: oral etoposide + anlotinib<br>* anlotinib 12mg qd, d1-14，21days/cycle oral etoposide 75mg qd，d1-10，21days/cycle<br>* Other names: there is no other intervention name;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective response rate（ORR） | The ORR will be defined as the proportion of patients in the Efficacy Evaluable patient Set who achieve complete response (CR) and partial response (PR) | up to 1 year after the last patient enrolled | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival（PFS） | PFS will be defined as the time from first dose of study drug until documentation of disease progression or death from any cause | up to 1 year after the last patient enrolled | 
| Incidence and Severity of adverse events | hematologic，hepatotoxicity，Incidence of hypertension，Incidence of proteinuria | approximately 1.5 years |