| Eligibility |
Inclusion Criteria:
1. Ages 10-70, both male and female.
2. The Eastern Collaborative Oncology Group (ECOG) physical status score was 0-1.
Subjects with amputation can be relaxed up to 2 points.
3. The expected survival time was =3 months.
4. Subjects with bone and soft tissue sarcomas with distant metastases or locally
advanced disease who were not considered suitable for surgical treatment by the
investigator.
5. Patients who had been treated with apatinib or anlotinib in the past, and the efficacy
was evaluated as CR\PR\SD\PD, and had no response to other systemic therapy after drug
resistance, or had reprogression after more than 3 months.
6. There were measurable lesions that met RECIST1.1 criteria.
7. All acute toxicities from previous antitumor therapy or surgery resolved to grade 0-1
(according to NCI-CTCAE, version 4.03) or to enrollment/exclusion criteria by day 1 of
the first cycle (C1D1), except for toxicities such as hair loss that the investigator
considered to pose no safety risk to the subject.
8. Adequate organ and bone marrow function is defined as follows:
Blood routine (no blood transfusion, no G-CSF, no medication correction within 14 days
before screening) :
Neutrophil count (ANC)=1,500/mm3(1.5×109/L); Platelet count
(PLT)=100,000/mm3(100×109/L); Hemoglobin (Hb)=9g/dL(90g/L);
Blood biochemical:
Serum creatinine (Cr)=1.5× upper limit of normal (ULN) or creatinine clearance
(Cockroft-Gault formula)=60ml/min; Total bilirubin (TBIL)=1.5×ULN; Aspartate
aminotransferase (AST) or alanine aminotransferase (ALT) levels =2.5×ULN, and subjects
with liver metastases should =5×ULN;
Blood coagulation function:
International normalized ratio (INR)=1.5, prothrombin time (PT) and activated partial
thromboplastin time (APTT)=1.5×ULN;
9. Urine routine: urinary protein <2+; If urine protein =2+, 24-hour urine protein
quantification must show protein =1g;
10. Thyroid function: Thyroid stimulating hormone (TSH)=ULN; FT3(T3) and FT4(T4) levels
should be examined if they are abnormal, and normal FT3(T3) and FT4(T4) levels can be
selected.
11. Female subjects of reproductive age must have a negative serum pregnancy test within 7
days prior to medication and be willing to use a medically approved highly effective
contraceptive (e.g., intrauterine device, birth control pill, or condom) during the
study period and within 3 months after the last administration of the study drug; Male
subjects with a female partner of reproductive age were required to undergo surgical
sterilization or consent to use an effective method of contraception during the study
period and for 3 months after the last study dose.
12. I have AGREED and signed the informed CONSENT, and I am willing AND ABLE TO comply
with the planned visit, study treatment, laboratory tests and other trial procedures.
Exclusion Criteria:
1. C1D1 received the following treatments in the previous 4 weeks:
Radiotherapy, surgery, chemotherapy, immunotherapy for tumors. Other investigational
drugs. Get live attenuated vaccine.
2. Surgery and/or radiation therapy for bone and soft tissue sarcomas were planned during
the study.
3. Previous use of immunosuppressive drugs within 14 days prior to C1D1, excluding nasal
spray and inhaled corticosteroids or physiological doses of systemic steroid hormones
(i.e., no more than 10mg/ day of prednisolone or an equivalent physiological dose of
another corticosteroid).
4. Severe infection (such as the need for intravenous antibiotic, antifungal, or
antiviral medication) within 4 weeks prior to C1D1, or unexplained fever >38.5°C
during the screening period/before the first dose.
5. Hypertension that is not well controlled with antihypertensive medication (systolic
blood pressure > 140 mmHg or diastolic blood pressure >90mmHg).
6. Significant bleeding symptoms or clear bleeding tendency occurred within 3 months
before C1D1, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline
fecal occult blood ++ and above, vasculitis, etc. Or arteriovenous thrombotic events
occurring within 6 months before C1D1, such as cerebrovascular accidents (including
transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein
thrombosis and pulmonary embolism; Long-term anticoagulant therapy with warfarin or
heparin or long-term antiplatelet therapy (aspirin =300mg/ day or clopidogrel =75mg/
day) may be required.
7. Active heart disease in the 6 months prior to C1D1, including myocardial infarction
and severe/unstable angina pectoris. Left ventricular ejection fraction <50% on
echocardiography, poorly controlled arrhythmias (including QTcF interval >450ms in men
and >470ms in women).
8. C1D1 had been diagnosed with any other malignancy within 3 years prior to C1D1, except
adequately treated basal or squamous cell skin cancer or carcinoma in situ of the
cervix.
9. Known allergy to the study drug or any of its excipients.
10. Human immunodeficiency virus (HIV) infection, active hepatitis B (hepatitis B surface
antigen positive and HBVDNA=500IU/ml), and hepatitis C (hepatitis C antibody positive
and HCV-RNA above the detection limit of the assay).
11. Concomitant diseases (e.g., poorly controlled hypertension, severe
diabetes,neurological or mental disorders, etc.) or any other conditions that, in the
judgment of the investigator, seriously endanger the safety of the subjects, may
confounding the results of the study, or interfere with the completion of the study.
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