Anlotinib Hydrochloride Combined With Liposomal Doxorubicin in the Treatment of Locally Advanced or Metastatic Soft Tissue Sarcoma

Inclusion Criteria:

• Signed the informed consent form prior to patient entry;

• ≥ 14 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, alveolar soft tissue sarcoma, andother sarcomas. The following histologies are excluded: embryonic rhabdomyosarcoma,chondrosarcoma, osteosarcoma, gastrointestinal stromal tumor and Ewing sarcoma/primaryneuroectodermal tumor.

• Previously without anthracyclines or other anti-tumor drugs

• 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 × 10^9 / L, Platelet count (PLT) ≥ 80 × 10^9 / 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 anlotinib or any other VEGFR tyrosine kinase inhibitor (such assunitinib, sorafenib, bevacizumab, imatinib, famitinib, apatinib, regorafenib andother 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 central nervous system metastases.

• Imaging (CT or MRI) shows tumor lesions from large vessels ≤ 5 mm, the tumor is verylikely to invade the important blood vessels and cause fatal hemorrhage, or theformation of tumor 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 uncontrollable hypertension (systolic blood pressure ≥140 mmHg or diastolic bloodpressure ≥90 mmHg, despite optimal drug treatment).

• Arrhythmias with grade II and above myocardial ischemia or myocardial infarction, poorcontrol (including corrected QT interval(QTc) men ≥ 450 ms, women ≥ 470 ms).

• According to NYHA criteria, grade III to IV cardiac insufficiency, or cardiac colorDoppler ultrasound examination showed left ventricular ejection fraction (LVEF) <50%,myocardial infarction occurred within 6 months before enrollment, ≥ 2 congestive heartfailure (New York Heart Association ( NYHA) rating ), uncontrolled angina, clinicalpericardial disease, or electrocardiogram suggesting acute ischemia or activeconduction system abnormalities.

• Uncontrolled comorbid diseases, including but not limited to: poorly controlleddiabetes, persistent active infections, or mental illness or social condition that mayaffect a subject's adherence to the study.

• Patients with active hepatitis B or hepatitis C (hepatitis B: HBsAg-positive andhepatitis B virus(HBV) DNA ≥ 500 IU/mL; hepatitis C: hepatitis C virus(HCV)RNA-positive and abnormal liver function), or active infection requiring antimicrobialtreatment (eg Treated with antibacterial drugs, antiviral drugs, antifungal drugs)

• Renal insufficiency: urine routine indicates urinary protein ≥ ++, or confirmed 24-hour urine protein ≥ 1.0 g;

• 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 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.