Sarcoma
Conditions
Interventions
Group A:Penpulimab + Anlotinib Hydrochloride + Epirubicin(dose escalation)
Group B:Penpulimab + Anlotinib Hydrochloride + Epirubicin
Sponsors
Zhongshan Hospital of Fudan University
Eligibility
Sex/Gender
All
Age
16 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Aged 16 to 75 years old; 2. ECOG PS score 0-1; 3. Expected survival >=3 months; 4. Patients with distant metastasis or locally advanced soft tissue sarcoma diagnosed by pathology and determined by the investigator to be unsuitable for surgical treatment, according to the WHO (2013 edition) soft tissue tumor classification, and the pathological types that are moderately sensitive to anthracycline chemotherapy and above ,mainly includes: High-grade dedifferentiated liposarcoma (G2, G3), pleomorphic liposarcoma, mixed liposarcoma, fibrosarcoma, myxofibrosarcoma, pleomorphic undifferentiated sarcoma, leiomyosarcoma, angiosarcoma, pleomorphic rhabdomyosarcoma, Synovial sarcoma, epithelioid sarcoma, malignant peripheral nerve sheath tumor, etc.; the special rare subtype of soft tissue sarcoma will be evaluated by the investigator for inclusion. Except for the following types: Myxoid/round cell liposarcoma, G1 dedifferentiated liposarcoma, clear cell sarcoma, endometrial stromal tumor, alveolar soft-part sarcoma, extraskeletal myxoid chondrosarcoma, osteosarcoma, chondrosarcoma, Ewing sarcoma/primary Neuroectodermal tumors, embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma, gastrointestinal stromal tumor (GIST). 5. The cumulative dose of anthracycline used in patients who have received anthracyclines during the previous perioperative period and relapse or metastasis occurs more than 6 months after stopping the drug should not exceed the specific dose. Doxorubicin (ADM): 400 mg/m2 Epirubicin (EPI): 600 mg/m2 Pirubicin (THP): 800 mg/m2 6. At least 1 measurable lesion >=1cm; 7. The main organs are functioning normally and meet the following criteria within 7 days before treatment: (1) The standard of routine blood examination must be met (no blood transfusion and blood products within 14 days, no correction with G-CSF and other hematopoietic stimulating factors): 1) Hemoglobin (HB) >=90g/L; 2) The absolute value of neutrophils (ANC) >=1.5x10^9/L; 3) Platelets (PLT) >=75x10^9/L (2) The biochemical inspection shall meet the following standards: 1) Total bilirubin (TBIL) =60ml/min; (3) Urine protein= lower limit of normal value (60%) (6) Thyroid function: TSH<= ULN; if abnormal, T3 and T4 levels should be considered, and if T3 and T4 levels are normal, they can be included in the group; 8. Women of childbearing age must have taken reliable contraceptive measures or undergo a pregnancy test (serum or urine) within 7 days before enrollment, and the result is negative, and are willing to adopt appropriate methods during the trial and 8 weeks after the last trial drug administration Contraception or sterilization. For men, they must agree to use appropriate methods of contraception or have been surgically sterilized during the trial period and 8 weeks after the last trial drug administration; 9. Sign the informed consent form with the consent of the person, and the compliance is good (for minors aged 16-18, the consent of the subject and his parents or legal guardian must be obtained to sign the informed consent form).
Exclusion criteria
Exclusion criteria: 1. Received anti-tumor therapy, including radiotherapy and surgery, within 4 weeks before enrollment. Received perioperative chemotherapy, palliative chemotherapy or other molecular targeted therapy within 6 months before enrollment; 2. Have previously received PD-1/PD-L1/CTLA-4 antibodies or anti-angiogenic drugs (such as sunitinib, sorafenib, regorafenib, bevacizumab, imatinib, Apatinib, etc.) treatment; 3. Plan to undergo surgery or radiotherapy during the study period; 4. Judging by imaging studies, there is a central nervous system metastasis; 5. Have used immunosuppressive drugs within 14 days before enrollment; 6. Any history of active immunity or autoimmune disease, or known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation; 7. Active or uncontrolled serious infection (=CTC AE grade 2 infection) occurred within 4 weeks before enrollment; 8. A history of hypertension, which cannot be well controlled after drug treatment (systolic blood pressure =140mmHg or diastolic blood pressure =90mmHg); 9. There were clinically significant bleeding symptoms or a clear bleeding tendency within three months before enrollment; 10. Patients with grade I or higher myocardial ischemia or myocardial infarction, arrhythmia (including QTc =480ms), and grade =2 congestive heart failure (New York Heart Association (NYHA) classification) within 6 months before enrollment; 11. Other malignant tumors were diagnosed within 3 years before enrollment; 12. HIV positive, liver cirrhosis, decompensated liver disease, active hepatitis or chronic hepatitis require antiviral treatment; 13. Participated in other anti-tumor drug clinical trials within 4 weeks before enrollment; 14. Those who have a history of psychotropic drug abuse and cannot be quit or have mental disorders; 15. According to the judgment of the investigator, there is a serious hazard to the safety of the patient, which may confuse the results of the study, or affect the patient's concomitant disease or any other situation that affects the completion of the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PFS; | — |
Secondary
| Measure | Time frame |
|---|---|
| DCR;ORR;PFS rate at 3m/6m;OS;2y OS rate;AE;SAE; | — |
Countries
China
Contacts
Public ContactZhou Yuhong
Zhongshan Hospital of Fudan University
Outcome results
None listed