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

This is an interventional treatment trial for Soft Tissue Sarcoma Read More

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, standard Treatment failure or no standard treatment regimen, mainly including liposarcoma, leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma, fibrosarcoma, clear cell sarcoma, angiosarcoma, epithelioid sarcoma, malignant peripheral nerve sheath tumor, undifferentiated sarcoma, Ewing's sarcoma, rhabdomyosarcoma, dermatofibrosarcoma protuberans, myofibroblastic sarcoma, malignant solitary fibroma, post-radiotherapy sarcoma, etc. (except gastrointestinal stromal tumor, etc.). Pathological subtypes without standard treatment options can receive 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 of disease 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 of neutrophils ≥ 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 first dose, 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 CNS metastases requiring hormone therapy within 28 days before the first dose, or lesions involving the brainstem or pia mater;
• Screening patients whose tumor has invaded around important blood vessels by imaging at the early stage or the investigators judged that the tumor is very likely to invade important blood vessels and cause massive hemorrhage;
• Patients with clinical symptoms or pleural effusion, ascites, and pericardial effusion that need to be drained during the screening period;
• Currently or in the past with other malignant tumors (except for adequately treated basal cell carcinoma of the skin or squamous cell carcinoma, carcinoma in situ of the cervix), unless radical treatment has been performed and there is no evidence of recurrence and metastasis within the past 5 years;
• Received aurora kinase inhibitor or VEGF/VEGFR inhibitor therapy in the past such as sunitinib, bevacizumab, apatinib, endo, pazopanib, regorafenib, lenvatinib, etc. ( for patients who are suitable for anlotinib treatment, only those who cannot receive anlotinib for various reasons are allowed to be enrolled in this study, and patients who have received anlotinib in the past are prohibited from entering this study);
• First-time medication: Those who have used anti-tumor therapy such as radiation therapy, chemotherapy, immunotherapy, and targeted therapy within the previous 28 days;
• Those who are allergic to any component or excipient of the test drug or have contraindications;
• Those who have used it within 28 days before the first drug use Investigational drugs or devices;
• Major surgical operations (such as craniotomy, thoracotomy or laparotomy) or severe unhealed wounds, ulcers or fractures, etc. have been received within 28 days before the first drug use;
• Screening period The original treatment toxicity has not been recovered, and there are still toxic reactions above grade 1 (except for alopecia) that meet the criteria of CTCAE 5.0;
• There are uncontrolled or important cardiovascular diseases, including: 6 times before the first administration of the study drug New York Heart Association (NYHA) class II or higher congestive heart failure, unstable angina, myocardial infarction, or arrhythmias requiring treatment at screening within one month, and left ventricular ejection fraction (LVEF) <50%; History of primary cardiomyopathy (eg, dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, indeterminate cardiomyopathy); Clinically significant QTc interval prolongation medical history, or QTc interval >470ms in women and >450ms in men during the screening period; Symptomatic coronary heart disease requiring drug treatment during the screening period; Concurrent use of ≥3 antihypertensive drug components within 14 days before the first dose treatment records, or systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg during the screening period (at rest, with an interval of about 5 minutes, three consecutive measurements, and the average value); Hypertension has occurred in the past crisis or hypertensive encephalopathy; During the screening period, there are other patients who are judged by the investigator to be unsuitable for inclusion. Cardiovascular diseases.
• Presence of interstitial lung disease or pulmonary fibrosis or pulmonary inflammation requiring treatment on chest imaging during the screening period, or a history of pneumonitis receiving oral or intravenous steroids within 6 months prior to the first dose;
• The screening period: there are obvious gastrointestinal abnormalities, which may affect the intake, transport or absorption of the drug (such as inability to swallow, chronic diarrhea, intestinal obstruction, after small bowel resection, etc.), or total gastrectomy, or before the first drug History of gastrointestinal perforation and/or fistula within 6 months;
• 24-hour urine protein quantitative test must be performed when urine protein is ≥2+ in routine urine examination during the screening period;
• Active bleeding within 2 months before the first medication, or taking anticoagulant drugs during the screening period (such as warfarin, phenylpro- coumarin, low-dose aspirin, low-molecular-weight heparin, etc.), or during the screening period, the investigator judged that there is a high risk of bleeding (such as esophageal and gastric varices with bleeding risk, locally active ulcer lesions, positive fecal occult blood cannot rule out gastrointestinal bleeding, intermittent hemoptysis, etc.);
• Before the first medication 6 Thrombotic events such as deep vein thrombosis or pulmonary embolism or cerebrovascular accident (implantable venous infusion port or catheter-derived thrombosis, which will be evaluated by the investigator to determine whether it can be enrolled) within one month;
• Systemic need for systemic Active infection for treatment (oral, intravenous infusion);
• HIV antibody positive screening test;
• Screening test positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with positive viral replication, hepatitis C antibody (HCV- Ab) positive with virus replication positive. (Note: qualitative testing is preferred, and quantitative testing for viral replication when needed);
• Any mental or cognitive impairment that may limit the understanding, execution of informed consent, and compliance with research;
• Long-term drug meditation;
• Pregnant or lactating women; women of childbearing age who are unwilling or unable to use effective methods of contraception during the entire treatment period of this trial and within 12 weeks after the last dose of the trial [Women of childbearing age include: Any menarche without successful artificial sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or nonmenopausal]; if the partner is a woman of childbearing age, the subject is not using effective contraception;
• The investigator believes that other conditions that are not suitable to participate in this trial, such as concomitant diseases, concomitant treatment or any abnormal laboratory tests, may interfere with the evaluation of the efficacy and safety results of the trial.