Tumor of biliary system
Conditions
Interventions
Experiment Group:Arotinib in combination with pd-1/pd-l1 and teggio
Sponsors
The First Affiliated Hospital of Zhengzhou University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1) The patients voluntarily joined the study and signed the informed consent form with good compliance; 2) Patients with unresectable or metastatic biliary tract tumors confirmed by histopathology or cytology: including intrahepatic cholangiocarcinoma (IHCC), extrahepatic cholangiocarcinoma (ehcc) and gallbladder carcinoma (GBC); 3) Patients who have not received systematic treatment, or who have received (New) adjuvant treatment / radical treatment until the end of the disease recurrence time >6 months; 4) According to recist1.1, there is at least one measurable lesion or assessable lesion; 5) Male or female patients aged 18-75 years; 6) ECoG score: 0-1; 7) Life expectancy = 3 months; 8) The organ function is sufficient, and the following laboratory test values are required during screening: (1) The blood routine examination standard shall be met (no blood transfusion and blood products within 14 days, no hematopoietic factor correction): ? hemoglobin content (HB) = 90g/l; ? neutrophil count (ANC) = 1.5 × 109/L ? platelet count (PLT) = 75 × 109/L ? white blood cell count (WBC) = 3.0 × 109/L? (2) Biochemical examination shall meet the following standards: ? total serum bilirubin (TBIL) = 1.5 times the upper limit of normal value (ULN); ? ALT and AST = 2.5uln; ? Cr = 1.5uln or creatinine clearance rate (CCR) = 60ml/min (Cockcroft Gault formula); ? serum albumin = 25 g/l (2.5 g/dl) ? for subjects with liver metastasis, AST and ALT must be = 5 x ULN, and leukocyte = 4 × 109/l, platelets without blood transfusion = 100 × 109/l, absolute value of neutrophils (ANC) without granulocyte stimulating factor treatment = 1.5 × 109/l, hemoglobin = 90 g/l (3) Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) = the lower limit of normal value (50%). (4) Adequate coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) = 1.5 times ULN; 9) Fertile women must take effective contraceptive measures during the study period, and at least 6 months after the last administration and chemotherapy. It is recommended to take contraceptive measures at least 3 months before the administration of the study drug; Men who were not sterilized were required to take effective contraceptive measures for at least 6 months during the study period, after the last administration and after chemotherapy. It is recommended that contraceptive measures be taken at least 3 months before the administration of the study drug.
Exclusion criteria
Exclusion criteria: 1) Patients who have received arotinib hydrochloride treatment or any anti-PD-1, anti-PD-L1, anti-CTLA-4 antibody treatment within the past three months; 2) Have a history of immune deficiency, including HIV test positive or suffering from other acquired or congenital immune deficiency diseases, or have a history of organ transplantation; 3) Patients with active hepatitis B or C and active pulmonary tuberculosis; 4) CT showed definite ulcerative lesions or positive occult blood in stool; 5) One month before enrollment, he had a history of abnormal bleeding (except epistaxis); 6) Previously received allogeneic bone marrow transplantation or organ transplantation; 7) Congenital pulmonary fibrosis, drug-induced pneumonia, organized pneumonia, or CT confirmed active pneumonia; 8) Live attenuated vaccine was injected within 4 weeks before the start of the study, or it is expected that live attenuated vaccine will be injected 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) Symptomatic central nervous system metastases and / or cancerous meningitis are known. Patients with a history of central nervous system metastasis or spinal cord compression can be included in the study if they have clearly received treatment and their clinical performance is stable after stopping anticonvulsants and steroids for 4 weeks before the first administration. 11) There are many factors affecting oral medication (such as inability to swallow, chronic diarrhea, intestinal obstruction, etc.); 12) Peripheral neuropathy = NCI CTCAE grade 2; 13) The load of liver metastases accounted for more than 60% of the total liver volume; 14) Patients with bone metastases at risk of paraplegia; 15) Patients with any severe and / or uncontrolled diseases, including: ? patients with unsatisfactory blood pressure control (systolic blood pressure = 150 mmHg or diastolic blood pressure = 100 mmHg) using antihypertensive drugs; Patients with myocardial ischemia or myocardial infarction above grade II and arrhythmia (including QT interval = 480ms); According to NYHA standard, patients with grade III-IV cardiac insufficiency or patients with left ventricular ejection fraction (LVEF) 1.5 or aptt>1.5 × ULN), with bleeding tendency or undergoing thrombolytic or anticoagulant therapy. It is known that there are hereditary or acquired bleeding and thrombotic tendencies, such as hemophilia, coagulation skill disorder, thrombocytopenia, hypersplenism, etc. Patients with obvious cough blood or daily hemoptysis of half a teaspoon (2.5 ml) or more within 2 months before entering the study. There were clinically significant bleeding symptoms or clear bleeding tendency within 3 months before entering the study, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood + + or above, or suffering from vasculitis. Long term anticoagulant therapy with warfarin or heparin or long-term antiplatelet therapy (aspirin = 300 mg/ day or clopidogrel = 75 mg/ day) is required. 18) Majo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression Free Survival, PFS; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate;disease control rate;1-year overall survival rate;Duration of Response; | — |
Countries
China
Contacts
Public ContactSun Yuling
Outcome results
None listed