A Single-center, Prospective, Two Cohort Study of Surufatinib Combined With AG or AG in the First-line Treatment of Locally Advanced or Metastatic Pancreatic Cancer

Exclusion Criteria

• •The study proposal shall be excluded if any of the following criteria are met:
• •1. Participated in clinical trials of other antitumor drugs within 4 weeks before enrollment;
• •2. Prior treatment with VEGFR inhibitors or prior treatment with immune checkpoint inhibitors;
• •3. Patients with BRCA1/2 germ line mutation;
• •4. Patients with obstructive jaundice but failing to reach the expected yellow reduction;
• •5. Have had other malignancies within the past 5 years, other than basal cell or squamous cell carcinoma of the skin after radical surgery, or carcinoma in situ of the cervix;
• •6. Patients who have had or currently have any brain metastases;
• •7. The investigators determined that liver metastases accounted for 70% or more of the total liver volume;
• •8. Had received any surgery (except biopsy) or invasive treatment or operation within 4 weeks prior to inclusion, and the surgical incision was not completely healed (except intravenous catheterization, puncture drainage, internal/external drainage for obstructive jaundice, etc.);
• •9. Uncontrolled pleural effusion, pericardial effusion or ascites requiring drainage;
• •10. Local antitumor therapy, such as hepatic artery interventional embolization, liver metastasis cryoablation or radiofrequency ablation, was received within 4 weeks before enrollment;
• •11. Electrolyte abnormalities identified by the investigator as clinically significant;
• •12. The patient has medically uncontrolled hypertension, as follows: systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg;
• •13. Urine routine indicated urinary protein ≥2+ and 24-hour urinary protein volume \> 1.0g;
• •14. Patients whose tumors are judged to be at high risk of invading vital blood vessels and causing fatal haemorrhage during the follow-up study;
• •15. Patients with significant evidence or history of bleeding tendency within 3 months prior to enrollment (bleeding within 3 months \> 30 mL, hematemesis, black feces, blood in stool), hemoptysis (within 4 weeks \> 5 mL fresh blood); A history of hereditary or acquired bleeding or a coagulation disorder. Have clinically significant bleeding symptoms or definite bleeding tendency within 3 months, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, etc.;
• •16. Clinically significant cardiovascular disease, including but not limited to acute myocardial infarction, severe/unstable angina, or coronary artery bypass grafting within 6 months prior to enrollment; New York Heart Association (NYHA) Grades for Congestive Heart Failure \> Level 2; Ventricular arrhythmias requiring medical treatment; Electrocardiogram (ECG) showed a QT c interval ≥480 ms;
• •17. Active or uncontrolled severe infection (≥CTCAE grade 2 infection);
• •18. Unmitigated toxic reactions higher than CTCAE grade 2 or above due to any previous anticancer therapy, excluding grade 2 or less neurotoxicity due to alopecia, lymphocytopenia, and oxaliplatin;
• •19. Women who are pregnant (positive pregnancy test before medication) or breastfeeding;
• •20. Any other medical condition, clinically significant metabolic abnormality, physical abnormality or laboratory abnormality, which, in the investigator's judgment, the patient has a medical condition or condition that is reasonably suspected to be unsuitable for the use of the study drug (such as the presence of epileptic seizures requiring treatment), or which would interfere with the interpretation of the study results, or place the patient at high risk;
• •21. Known human immunodeficiency virus (HIV) infection; A known history of clinically significant liver disease, including viral hepatitis \[active HBV infection must be ruled out as a known carrier of hepatitis B virus (HBV), i.e. positive HBV DNA (\>1×104 copies/mL or \>2000 IU/ml); known hepatitis C virus infection (HCV) and HCV RNA positive (\>1×103 copies /mL), or other hepatitis, cirrhosis;
• •22. The presence of any active, known or suspected autoimmune disease (including but not limited to: myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, enteritis, multiple sclerosis, vasculitis, glomerulonephritis, uveitis, pituitaritis, hyperthyroidism, etc.);
• •23. Allergy or suspected allergy to the study drug or similar drug;
• •24. In the investigator's judgment, the patient had other factors that might affect the study results or lead to the termination of the study, such as alcoholism, drug abuse, other serious medical conditions (including mental illness) requiring concomitant treatment, serious laboratory abnormalities, and family or social factors that would affect the patient's safety.