Phase II Study of Chiauranib Capsule in Advanced or Unresectable Soft Tissue Sarcoma

Inclusion Criteria:

• Age 18-75 years (including cutoff values) when signing the informed consent form,regardless of gender;
• All pathologically diagnosed advanced or unresectable soft tissue sarcomas, standardTreatment failure or no standard treatment regimen, mainly including liposarcoma,leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma/malignantfibrous histiocytoma, fibrosarcoma, clear cell sarcoma, angiosarcoma, epithelioidsarcoma, malignant peripheral nerve sheath tumor, undifferentiated sarcoma, Ewing'ssarcoma, rhabdomyosarcoma, dermatofibrosarcoma protuberans, myofibroblastic sarcoma,malignant solitary fibroma, post-radiotherapy sarcoma, etc. (except gastrointestinalstromal tumor, etc.). Pathological subtypes without standard treatment options canreceive first-line treatment, including but not limited to acinar soft tissue sarcoma,malignant peripheral nerve sheath tumor, clear cell sarcoma, epithelioid sarcoma,well-differentiated/dedifferentiated liposarcoma, post-radiotherapy sarcoma, etc. ;
• According to the RECIST1.1 criteria, there is at least one measurable target lesion,and the lesions of radiotherapy or local area therapy must have imaging evidence ofdisease progression before they can be regarded as target lesions;
• ECOG physical fitness score 0-1 points;
• The main organ functions meet the following criteria: Blood routine: absolute value ofneutrophils ≥ 1.5×109/L, platelets ≥75×109/L, hemoglobin ≥ 80 g/L (not allowed within 14 days before the first medication); Blood biochemistry: serum creatinine (Cr)≤1.5×Upper limit of normal (ULN); total bilirubin≤1.5×ULN, AST, ALT≤2.5× ULN (≤5×ULN if liver metastases); Coagulation function: International Normalized Ratio (INR) < 1.5 (anticoagulation therapy is not allowed within 14 days before the firstdose, except for prophylactic anticoagulation therapy at a stable dose).
• Expected survival time ≥ 3 months; 7. Voluntary signed written informed consent.

Exclusion Criteria:

• Active central nervous system (CNS) symptoms during the screening period and/or CNSmetastases requiring hormone therapy within 28 days before the first dose, or lesionsinvolving the brainstem or pia mater;
• Screening patients whose tumor has invaded around important blood vessels by imagingat the early stage or the investigators judged that the tumor is very likely to invadeimportant blood vessels and cause massive hemorrhage;
• Patients with clinical symptoms or pleural effusion, ascites, and pericardial effusionthat need to be drained during the screening period;
• Currently or in the past with other malignant tumors (except for adequately treatedbasal cell carcinoma of the skin or squamous cell carcinoma, carcinoma in situ of thecervix), unless radical treatment has been performed and there is no evidence ofrecurrence and metastasis within the past 5 years;
• Received aurora kinase inhibitor or VEGF/VEGFR inhibitor therapy in the past such assunitinib, bevacizumab, apatinib, endo, pazopanib, regorafenib, lenvatinib, etc. ( forpatients who are suitable for anlotinib treatment, only those who cannot receiveanlotinib for various reasons are allowed to be enrolled in this study, and patientswho have received anlotinib in the past are prohibited from entering this study);
• First-time medication: Those who have used anti-tumor therapy such as radiationtherapy, chemotherapy, immunotherapy, and targeted therapy within the previous 28days;
• Those who are allergic to any component or excipient of the test drug or havecontraindications;
• Those who have used it within 28 days before the first drug use Investigational drugsor devices;
• Major surgical operations (such as craniotomy, thoracotomy or laparotomy) or severeunhealed wounds, ulcers or fractures, etc. have been received within 28 days beforethe first drug use;
• Screening period The original treatment toxicity has not been recovered, and there arestill toxic reactions above grade 1 (except for alopecia) that meet the criteria ofCTCAE 5.0;
• There are uncontrolled or important cardiovascular diseases, including: 6 times beforethe first administration of the study drug New York Heart Association (NYHA) class IIor higher congestive heart failure, unstable angina, myocardial infarction, orarrhythmias requiring treatment at screening within one month, and left ventricularejection fraction (LVEF) <50%; History of primary cardiomyopathy (eg, dilatedcardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricularcardiomyopathy, restrictive cardiomyopathy, indeterminate cardiomyopathy); Clinicallysignificant QTc interval prolongation medical history, or QTc interval >470ms in womenand >450ms in men during the screening period; Symptomatic coronary heart diseaserequiring drug treatment during the screening period; Concurrent use of ≥3antihypertensive drug components within 14 days before the first dose treatmentrecords, or systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHgduring the screening period (at rest, with an interval of about 5 minutes, threeconsecutive measurements, and the average value); Hypertension has occurred in thepast crisis or hypertensive encephalopathy; During the screening period, there areother patients who are judged by the investigator to be unsuitable for inclusion.Cardiovascular diseases.
• Presence of interstitial lung disease or pulmonary fibrosis or pulmonary inflammationrequiring treatment on chest imaging during the screening period, or a history ofpneumonitis receiving oral or intravenous steroids within 6 months prior to the firstdose;
• The screening period: there are obvious gastrointestinal abnormalities, which mayaffect the intake, transport or absorption of the drug (such as inability to swallow,chronic diarrhea, intestinal obstruction, after small bowel resection, etc.), or totalgastrectomy, or before the first drug History of gastrointestinal perforation and/orfistula within 6 months;
• 24-hour urine protein quantitative test must be performed when urine protein is ≥2+ inroutine urine examination during the screening period;
• Active bleeding within 2 months before the first medication, or taking anticoagulantdrugs during the screening period (such as warfarin, phenylpro- coumarin, low-doseaspirin, low-molecular-weight heparin, etc.), or during the screening period, theinvestigator judged that there is a high risk of bleeding (such as esophageal andgastric varices with bleeding risk, locally active ulcer lesions, positive fecaloccult blood cannot rule out gastrointestinal bleeding, intermittent hemoptysis,etc.);
• Before the first medication 6 Thrombotic events such as deep vein thrombosis orpulmonary embolism or cerebrovascular accident (implantable venous infusion port orcatheter-derived thrombosis, which will be evaluated by the investigator to determinewhether it can be enrolled) within one month;
• Systemic need for systemic Active infection for treatment (oral, intravenousinfusion);
• HIV antibody positive screening test;
• Screening test positive for hepatitis B surface antigen (HBsAg) or hepatitis B coreantibody (HBcAb) with positive viral replication, hepatitis C antibody (HCV- Ab)positive with virus replication positive. (Note: qualitative testing is preferred, andquantitative testing for viral replication when needed);
• Any mental or cognitive impairment that may limit the understanding, execution ofinformed consent, and compliance with research;
• Long-term drug meditation;
• Pregnant or lactating women; women of childbearing age who are unwilling or unable touse effective methods of contraception during the entire treatment period of thistrial and within 12 weeks after the last dose of the trial [Women of childbearing ageinclude: Any menarche without successful artificial sterilization (hysterectomy,bilateral tubal ligation or bilateral oophorectomy) or nonmenopausal]; if the partneris a woman of childbearing age, the subject is not using effective contraception;
• The investigator believes that other conditions that are not suitable to participatein this trial, such as concomitant diseases, concomitant treatment or any abnormallaboratory tests, may interfere with the evaluation of the efficacy and safety resultsof the trial.