Tumor of biliary system
Conditions
Interventions
Experiment Group:Penpulimab combined with anlotinib
Sponsors
The Second Affiliate Hospital of Air Force Medical University/Tangdu Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Age: 18-75; Both men and women. 2. For gallbladder cancer or intrahepatic and extrahepatic cholangiocarcinoma confirmed by histopathology or cytopathology, according to RECIST v1.1, there is at least one measurable lesion; 3. Patients who have failed or are not suitable for standard first-line treatment in the past. Failure of first-line chemotherapy was defined as: disease progression occurred during treatment or within 6 months after the last treatment; Or intolerable due to toxic side effects during treatment. It mainly includes the following situations: A. Combination chemotherapy drugs with first-line treatment time = 1 cycle; B. Allow neoadjuvant or adjuvant chemotherapy in the early stage. If disease progression/recurrence occurs during neoadjuvant/adjuvant treatment or within 6 months after the end of treatment, it is considered that neoadjuvant/adjuvant treatment is the failure of first-line systemic chemotherapy for progressive disease; C. The previous first-line standard chemotherapy does not include anti-angiogenesis small-molecule inhibitors or monoclonal antibodies and tumor immune-related drugs); 4. ECOG score: 0-1. 5. The expected survival period is = 12 weeks. 6. Have not been treated with anti-angiogenic drugs other than bevacizumab. 7. The function of main organs is normal, that is, they meet the following standards: (1) Blood routine examination: a. HB = 90 g/L; (No blood transfusion within 14 days) b. ANC = 1.5 × 10^9/L c. PLT =75 × 10^9/L (2) Biochemical examination: a. ALB = 30g/L; (ALB is not transmitted within 14 days) b. ALT and AST<2.5ULN; In case of liver metastasis, ALT and AST = 5ULN; c. TBIL=2ULN; D. Plasma Cr = 1.5ULN, or creatinine clearance rate (CCr) = 60ml/min; 8. Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) = lower limit of normal value (50%). Coagulation function: activated partial thromboplastin time (APTT), international normalized ratio (INR), prothrombin time (PT) = 1.5XULN; 9. Subjects volunteered to join the study, signed the informed consent form, and were able to follow the visit and related procedures specified in the protocol. 10. Female subjects of childbearing age or male subjects whose sexual partners are female of childbearing age need to take effective contraceptive measures (such as intrauterine device [IUD], contraceptives or condoms) throughout the treatment period and 6 months after the treatment period; The serum or urine pregnancy test is negative within 7 days before the study enrollment, and must be a non-lactating patient; Men should agree to use contraception during the study period and within 6 months after the end of the study period.
Exclusion criteria
Exclusion criteria: 1) Patients who have previously been treated with VEGFR target inhibitor drugs, including arotinib hydrochloride capsules, or used other PD-1/PD-L1/CTLA-4 antibody therapy or other immunotherapy for PD-1/PD-L1/CTLA-4; 2) It has been confirmed that it is allergic to arotinib hydrochloride and/or its excipients as well as the components of pripriprizumab; 3) Within 5 years, the subject has previously or simultaneously suffered from other malignant tumors (except the cured skin basal cell carcinoma, prostate carcinoma in situ and cervical carcinoma in situ); 4) There is any active autoimmune disease or history of autoimmune disease (such as but not limited to: autoimmune hepatitis, interstitial pneumonia, enteritis, vasculitis, nephritis; asthma in which subjects need bronchodilator for medical intervention cannot be included); However, the following patients are allowed to be included: vitiligo, psoriasis, alopecia without systemic treatment, well controlled type I diabetes, hypothyroidism with normal thyroid function after replacement treatment; 5) It is necessary to use immunosuppressive agent, or systemic or absorbable local hormone treatment to achieve immunosuppressive effect (dose>10mg/day prednisone or other effective hormones), and it is still in use within 2 weeks after the first administration; 6) Those with multiple factors that affect oral medication (such as inability to swallow, postoperative gastrointestinal resection, chronic diarrhea and intestinal obstruction); 7) Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage; 8) Patients with any physical signs or medical history of bleeding regardless of severity; Patients with any bleeding or bleeding event = CTCAE level 3 within 4 weeks before the first administration; Or there are non-healing wounds, fractures, active ulcer of stomach and duodenum, ulcerative colitis and other digestive tract diseases, or there is active bleeding in unresectable tumors, or other conditions that may cause gastrointestinal bleeding and perforation determined by the researcher; 9) Those who have uncontrollable symptoms of brain metastasis, spinal cord compression, carcinomatous meningitis, or brain or leptomeningeal diseases found by CT or MRI during screening within 4 weeks before the first administration; 10) Within 4 weeks before the start of the study treatment, he has received approved or under research anti-tumor treatment, including but not limited to surgery, radiotherapy, bio-targeted therapy, interventional therapy Immunotherapy and anti-tumor traditional Chinese medicine treatment (subject to the indications in the Chinese medicine manual, and can also be included in the group after 2 weeks of washout period), etc. (Note: patients with chemotherapy less than 2 weeks; patients with oral targeted drugs less than 5 drug half-lives; or patients with oral fluorouracil drugs less than 14 days, mitomycin C and nitrosourea less than 6 weeks; patients with adverse events caused by previous treatment (excluding hair loss) not recovered to = CTCAE 1 degree); 11) Patients with any serious and/or uncontrolled disease, including: a: Patients with poor blood pressure control (systolic blood pressure = 150 mmHg or diastolic blood pressure = 90 mmHg) b: Unstable angina pectoris, myocardial infarction, = grade 2 congestive heart failure, or arrhythmia requiring treatment (including QTc = 480ms) occurred within 6 months after the first administration; c
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression Free Survival, PFS;disease control rate;overall survival; | — |
Countries
China
Contacts
Public ContactXilin Du
The Second Affiliate Hospital of Air Force Medical University/Tangdu Hospital
Outcome results
None listed