Gastric cancer
Conditions
Interventions
experimental group:Anlotinib + TQB2450 + S-1 + Oxaliplatin
Sponsors
The First Affiliated Hospital of Zhengzhou University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1) Patients voluntarily join this study, sign the informed consent form, and have good compliance; 2) Unresectable locally advanced or metastatic gastric cancer (including signet ring cell carcinoma, mucinous adenocarcinoma, liver adenocarcinoma); 3) Patients with the time from the end of previous (neo) adjuvant chemotherapy/adjuvant radiotherapy to disease recurrence > 6 months; 4) According to RECIST version 1.1, there is at least one measurable lesion or evaluable lesion; the measurable lesion should not have received local treatment such as radiotherapy (the lesion located in the area of previous radiotherapy, if it is confirmed to progress, and meets the RECIST1.1 standard , can also be used as the target lesion); 5) Male or female patients aged 18-75; 6) ECOG score: 0~1 point; 7)PD-L1 CPS <5; 8) Life expectancy = 3 months; 9) The organ function is sufficient, and the following laboratory test values are required to be met during screening: (1) Blood routine inspection standards must meet: ?Hemoglobin content (HB) = 90 g/L (no blood transfusion within 14 days); ?Absolute neutrophil count (ANC) =1.5×10^9/L; ?Platelet count (PLT) =100×10^9/L (without using interleukin 11 or TPO within 14 days); ? White blood cell count (WBC) = 4.0×10^9/L (no use of granulocyte stimulating factor within 14 days). (2) Biochemical examination must meet the following standards: ? Serum total bilirubin (TBIL) = 1.5 times the upper limit of normal (ULN); ?ALT and AST=2.5 ULN; ?Cr=1.5ULN or creatinine clearance rate (CCr)=60 ml/min, (Cockcroft-Gault formula); ?Serum albumin = 25 g/L (2.5 g/dL) ?For subjects with liver metastases, AST and ALT must be =5 x ULN, white blood cells = 4×10^9/L, platelets without blood transfusion = 100×10^9/L, neutrophils without treatment with granulocyte-stimulating factor Value (ANC) = 1.5×10^9/L, hemoglobin = 90 g/L (3) Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) = the lower limit of normal (50%). (4) Sufficient coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) = 1.5 times ULN; Women of childbearing potential were required to use highly effective contraception during the study and for at least 6 months after the last dose and chemotherapy. It is recommended to start taking contraceptive measures at least 3 months before the administration of the study drug; non-sterilized men must be required to take effective contraceptive measures for at least 6 months during the study, after the last dose and after chemotherapy. Contraception is recommended to be initiated at least 3 months prior to study drug administration.
Exclusion criteria
Exclusion criteria: Patients with any of the following will not be enrolled in this study: 1) Patients who have previously received anlotinib hydrochloride treatment or any anti-PD-1, anti-PD-L1, anti-CTLA-4 antibody treatment; 2) Those with a history of immunodeficiency, including HIV-positive or other acquired or congenital immunodeficiency diseases, or those with a history of organ transplantation; 3) Patients with active hepatitis B or C, or active tuberculosis; 4) CT shows clear ulcerated lesions or positive fecal occult blood; 5) Self-reported history of abnormal bleeding (except epistaxis) 1 month before enrollment; 6) Previously received allogeneic bone marrow transplantation or organ transplantation; 7) Congenital pulmonary fibrosis, drug-induced pneumonia, organizing pneumonia, or active pneumonia confirmed by CT; 8) Have injected live attenuated vaccine within 4 weeks before the start of the study, or are expected to inject live attenuated vaccine during the trial or within 5 months after the end of the trial; 9) Systemic application of glucocorticoids or immunosuppressants within 2 weeks before the start of the test (note: inhaled glucocorticoids and mineralocorticoids are allowed); 10) Known symptomatic central nervous system metastases and/or cancerous meningitis. Patients with a history of central nervous system metastases or spinal cord compression were eligible if they were clearly treated and were clinically stable 4 weeks after stopping anticonvulsants and steroids prior to the first dose of the study. 11) There are multiple factors that affect oral medication (such as inability to swallow, chronic diarrhea and intestinal obstruction, etc.); 12) Peripheral neuropathy = NCI CTCAE grade 2; 13) There is an infection requiring antibiotics within 14 days before the start of the test; 14) The burden of liver metastases accounts for more than 50% of the entire liver volume; 15) Patients with bone metastases at risk of paraplegia; 16) Patients with any severe and/uncontrolled disease, including: ?Patients with unsatisfactory blood pressure control using antihypertensive drugs (systolic blood pressure = 150 mmHg or diastolic blood pressure = 100 mmHg); patients with grade II or above myocardial ischemia or myocardial infarction, arrhythmia (including QT interval = 480ms); NYHA standard, grade III-IV cardiac insufficiency, or patients with left ventricular ejection fraction (LVEF) 10mmol/L); ?Urine routine prompts urine protein = ++, and confirmed 24-hour urine protein quantity > 1.0 g; 17) Long-term unhealed wounds or fractures; 18) Abnormal coagulation function (INR>1.5 or APTT>1.5 × ULN), with bleeding tendency or receiving thrombolytic or anticoagulant therapy. Known hereditary or acquired bleeding and thrombosis tendency, such as: hemophilia, coagulation disorder, thrombocytopenia, hypersplenism, etc. Within 2 months before entering the study, there was obvious coughing up blood, or the amount of hemoptysis reached half a teaspoon (2.5 ml) or more per day. Had clinically significant bleeding symptoms or had a clear bleeding tendency within 3 months before entering the study, such as gastrointestinal bleeding, bleeding gastric ulcer, fecal occult blood ++ and above at baseline, or suffering from v
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate, ORR; | — |
Secondary
| Measure | Time frame |
|---|---|
| Disease Control Rate, DCR;Progression Free Survival, PFS;1-year Overall Survival rate;Duration of Response, DoR;Safety; | — |
Countries
China
Contacts
Public ContactYan-Ru Qin
The First Affiliated Hospital of Zhengzhou University
Outcome results
None listed