Camrelizumab and Chemotherapy With or Without Anlotinib as First-line Treatment for Advanced Gallbladder Cancer and Extrahepatic Cholangiocarcinoma

Exclusion Criteria

• •1\) Patients who have received anlotinib hydrochloride treatment or any anti-PD-1, anti-PD-L1, anti-CTLA-4 antibody treatment in the past;
• •2\) Patients with a history of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation;
• •3\) Patients with active hepatitis B or C, active pulmonary tuberculosis;
• •4\) Patients with liver metastasis burden accounting for more than 50% of the total liver volume;
• •5\) CT showed clear ulcerative lesions or positive stool occult blood;
• •6\) Self-reported history of abnormal bleeding (excluding epistaxis) one month before enrollment;
• •7\) Patients who have received allogeneic bone marrow transplantation or organ transplantation in the past;
• •8\) Congenital pulmonary fibrosis, drug-induced pneumonia, organizing pneumonia, or active pneumonia confirmed by CT;
• •9\) Injection of live attenuated vaccine within 4 weeks before the start of the study, or expected to be injected with live attenuated vaccine during the trial or within 5 months after the end of the trial;
• •10\) Systemic application of glucocorticoids or immunosuppressants within 2 weeks before the start of the trial (Note: inhaled glucocorticoids and mineralocorticoids are allowed);
• •11\) Multiple factors that affect oral medication (such as inability to swallow, chronic diarrhea and intestinal obstruction, etc.);
• •12\) ≥ NCI CTCAE grade 2 peripheral neuropathy;
• •13\) Infection requiring antibiotics within 14 days before the start of the trial;
• •14\) Patients with any severe and/or uncontrolled diseases, including: Patients with poor 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); patients with grade III-IV heart failure according to NYHA standards, or left ventricular ejection fraction (LVEF) \<50% indicated by cardiac ultrasound examination; Active or uncontrolled severe infection; Liver disease such as cirrhosis, decompensated liver disease, chronic active hepatitis; Poorly controlled diabetes (fasting blood glucose (FBG) \>10mmol/L); Urinalysis indicates urine protein ≥++, and confirms that the 24-hour urine protein quantification is \>1.0 g;
• •15\) Long-term unhealed wounds or fractures;
• •16\) Abnormal coagulation function (INR\>1.5 or APTT\>1.5 × ULN), bleeding tendency or receiving thrombolytic or anticoagulant treatment. Known hereditary or acquired bleeding and thrombotic tendencies, such as hemophilia, coagulation disorder, thrombocytopenia, hypersplenism, etc. Those who have coughed up blood or coughed up half a teaspoon (2.5 ml) or more of blood per day within 2 months before entering the study. Those who have clinically significant bleeding symptoms or have a clear bleeding tendency within 3 months before entering the study, such as gastrointestinal bleeding, bleeding gastric ulcer, baseline stool occult blood ++ and above, or vasculitis, etc. Long-term anticoagulation treatment with warfarin or heparin is required, or long-term antiplatelet therapy is required (aspirin ≥300 mg/day or clopidogrel ≥75 mg/day).
• •17\) Major surgery (craniotomy, thoracotomy or laparotomy) within 4 weeks before the study, or major surgery is expected during the study treatment, or non-diagnostic surgery within 4 weeks before the start of the trial;
• •18\) History of gastrointestinal perforation and/or fistula within 6 months before the treatment; or experience of arterial/venous thrombotic events, such as cerebrovascular accident (except stable cerebral infarction assessed by the investigator), deep vein thrombosis and pulmonary embolism;
• •19\) Clinically significant pleural effusion, including any pleural effusion found during physical examination, pleural effusion that has been treated before or is still in need of treatment. Patients with only a small amount of pleural effusion and ascites but no symptoms can be selected if the investigators assess that they do not need treatment;
• •20\) Patients with significant malnutrition;
• •21\) Patients with a history of psychotropic drug abuse and inability to quit or with mental disorders;
• •22\) Other histories of primary malignant tumors, except for the following: 1) Malignant tumors that have been completely relieved for at least 2 years before enrollment and do not require other treatment during the study; 2) Non-melanoma skin cancer or malignant lentigo that has been adequately treated and has no evidence of disease recurrence; 3) Carcinoma in situ that has been adequately treated and has no evidence of disease recurrence;
• •23\) Pregnant or breastfeeding female patients;
• •24\) Patients with serious concomitant diseases that, according to the investigators' judgment, endanger patient safety or affect the patient's completion of the study;
• •25)Participating in other trials within 30 days before the start of the trial, or planning to participate in other trials during the trial.