Anlotinib Hydrochloride Combined With Epirubicin and Ifosfamide for Soft Tissue Sarcoma Patients

Inclusion Criteria:

• Signed the informed consent form prior to patient entry;

• ≥ 18 years of age , regardless of gender；ECOG :0-1;Expected Survival Time: Over 3months;

• Histologically confirmed diagnosis of un-resectable or recurrent metastatic softtissue sarcoma, such as: leiomyosarcoma, synovial sarcoma, undifferentiatedpleomorphic sarcoma, liposarcoma , angiosarcoma and other sarcomas. The followinghistologies are excluded: alveolar Soft tissue sarcoma, rhabdomyosarcoma,chondrosarcoma, osteosarcoma, gastrointestinal stromal tumor, humeral cutaneousfibrosarcoma, Ewing sarcoma/primary neuroectodermal tumor, inflammatorymyofibroblastic sarcoma and malignant mesothelioma.

• Patients who were not treated with anthracyclines or other tyrosinase inhibitors orangiostatins within the first 6 months should be enrolled.

• Evaluable disease by imaging or physical exam or measurable disease defined as atleast one lesion that can be accurately measured according to RECIST version 1.1.

• normal main organs function as defined below: Hemoglobin (Hb) ≥ 80g / L, Neutrophils (ANC) ≥ 1.5 × 109 / L, Platelet count (PLT) ≥ 80 × 109 / L, Serum creatinine (Cr) ≤ 1.5 × normal upper limit (ULN) or creatinine clearance (CCr) ≥ 60ml / min, Blood ureanitrogen (BUN) ≤ 2.5 × normal upper limit (ULN); Total bilirubin (TB) ≤ 1.5 × ULN;Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; Ifaccompanied by liver metastases, ALT and AST ≤ 5 × ULN Albumin (ALB) ≥ 25 g/L. Dopplerultrasound assessment: left ventricular ejection fraction (LVEF) ≥ normal low limit (50%)

• Women of childbearing potential should agree to use and utilize an adequate method ofcontraception (such as intrauterine device，contraceptive and condom) throughouttreatment and for at least 6 months after study is stopped；the result of serum orurine pregnancy test should be negative within 7 days prior to study enrollment，andthe patients required to be non-lactating；Man participants should agree to use andutilize an adequate method of contraception throughout treatment and for at least 6months after study is stopped.

Exclusion Criteria:

• Prior treatment with any VEGFR tyrosine kinase inhibitor(such as sunitinib, sorafenib,bevacizumab, imatinib, famitinib, apatinib, regorafenib and other drugs).

• Systemic anti-tumor therapy, including cytotoxic therapy, signal transductioninhibitors, and immunotherapy, is planned for the first 4 weeks prior to enrollment orduring the study. Radiation radiotherapy (EF-RT) was performed within 4 weeks prior toenrollment.

• A history of other malignancy ≤ 3 years previous

• Known brain metastases.

• The investigator judged that during the follow-up study, the tumor is very likely toinvade the important blood vessels and cause fatal hemorrhage, or the formation oftumor thrombosis with large veins (iliac vessels, inferior vena cava, pulmonary veins,superior vena cava);

• The investigator judged that the presence of distinct pulmonary cavitary or necrotictumors;

• Serosal effusion with clinical symptoms requiring surgical management (includinghydrothorax and ascites pericardial effusion)

• with any severe and/or uncontrolled disease, including:1)Uncontrollable hypertension (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg, despiteoptimal drug treatment).2)Arrhythmias with grade II and above myocardial ischemia ormyocardial infarction, poor control (including corrected QT interval(QTc) men ≥ 450ms, women ≥ 470 ms) and ≥ 2 congestive heart failure (New York Heart Association (NYHA) rating).3)Poor control of diabetes (fasting blood glucose > 10mmol / L).4)Activeor uncontrolled serious infection (≥ Common Terminology Criteria for Adverse Event(CTCAE) grade 2 infection);5)Patients with active hepatitis B or hepatitis C (hepatitis B:HBsAg-positive and hepatitis B virus(HBV) DNA ≥ 500 IU/mL; hepatitis C: hepatitis Cvirus(HCV) RNA-positive and abnormal liver function), or active infection requiringantimicrobial treatment (eg Treated with antibacterial drugs, antiviral drugs,antifungal drugs);6)renal insufficiency: urine routine indicates urinary protein ≥ ++,or confirmed 24-hour urine protein ≥ 1.0 g;7)Patients with seizures and need treatment

• Abnormal coagulation (INR > 1.5 or prothrombin time (PT) > ULN + 4 seconds oractivated partial thromboplastin time(APTT) > 1.5 ULN), with bleeding tendency orundergoing thrombolytic or anticoagulant therapy.

• Patients treated with anticoagulants or vitamin K antagonists such as warfarin,heparin.

• significant coughing blood in the 2 months before enrollment, or daily hemoptysis of 2.5ml or more.

• history of psychotropic substance abuse who are unable to quit or have a mentaldisorder.

• Tendencies of hereditary or acquired hemorrhagic and thrombotic (such as hemophiliapatients, coagulopathy, thrombocytopenia, hypersplenism, etc.)

• Any major unhealed wound, ulcer, or fracture occurred in a patient who had undergonemajor surgery or trauma within 4 weeks and/or had any bleeding or bleeding episodeswhich the degree is bigger than CTCAE 3 grade within 4 weeks prior to enrollment.

• Active period digestive ulcers.

• Cavity sinus or perforation occurred within 6 months.

• Participated in other anti-tumor clinical trials within 4 weeks.

• Received a potent CYP3A4 inhibitor (such as ketoconazole, itraconazole, erythromycin,and clarithromycin) within 7 days, or received a potent CYP3A4 inducer within 12 daysprior to the study (eg. catarrh Treatment with imipramine, rifampicin andphenobarbital).

• Allergic reactions, hypersensitivity reactions or intolerance to anlotinibhydrochloride or its excipients.

• Pregnancy or lactation.

• The investigator believes that there are any conditions that may damage the subject orresult in the subject not being able to meet or perform the research request.