Biliary tumors
Conditions
Sponsors
General Hospital of Eastern Theater Command
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Be able to sign an informed consent form and demonstrate compliance with the requirements and limitations outlined in the ICF and the study protocol. 2. Failed to receive previous first-line standard treatment; Definition of failure: intolerability of toxic side effects, progression of disease during treatment or recurrence after completion of treatment; The definition of intolerance: hematologic toxicity of grade IV (platelet decline of grade III and above), non-hematologic toxicity of grade III and above] Note: Each line of drugs refers to the use of at least 1 cycle, whether single or multi-drug combination. 3. Age =18 years at screening time. 4. Histopathologically proven, unresectable advanced or metastatic biliary adenocarcinoma, including cholangiocarcinoma (intrahepatic or extrahepatic) and gallbladder carcinoma. 5. A World Health Organization (WHO) /ECOG Physical status (PS) of 0 or 1 at the time of enrollment. 6. At least 1 RECIST 1.1 compliant target lesion at baseline. 7. Adequate organ and bone marrow function, defined as: hemoglobin =9.0 g/dL, absolute neutrophil count =1.5×109/L, platelet count =100×109/L, serum bilirubin =2.0× upper limit of normal (ULN); These conditions do not apply to patients with proven Gilbert syndrome. Any clinically significant biliary obstruction should be resolved before randomization. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =2.5×ULN; For patients with liver metastasis, ALT and AST=5×ULN. Creatinine clearance >50 mL/min in urine or by Cockcroft-Gault (using actual body weight) every 24 hours. 8. Patients must have a life expectancy of at least 12 weeks at the time of screening. 9. Weight >30 kg. 10. Have detectable levels of HBV deoxyribonucleic acid (DNA) [according to local laboratory requirements, Patients with HBV infection (positive for hepatitis B surface antigen [HBsAg] and/or hepatitis B core antibody [anti-HBc]) =10 IU/mL or higher than the detection limit] must receive antiviral therapy in accordance with clinical institution practice prior to enrollment to ensure adequate viral suppression. Patients must maintain antiviral therapy during the study period and for 6 months after the last study treatment. Patients who test positive for anti-HBc but do not detect HBV-DNA (<10 IU/mL or below the detection limit according to local laboratory requirements) do not require antiviral therapy unless the HBV DNA exceeds 10 IU/mL or meets the detection limit set by the local laboratory during treatment. Patients with active co-infection of HBV and HCV and active co-infection of HBV and hepatitis D virus based on positive anti-HCV antibodies did not meet the criteria for inclusion.
Exclusion criteria
Exclusion criteria: 1. Exclusion from the study is required if any of the following criteria are met: 2. Ampullary carcinoma. 3.. Patients who had previously received small molecule drugs of the same VEGFR-TKI, such as anlotinib, sunitinib, sorafenib, lenvatinib, apatinib, etc.; (4) Clinically intervened biliary obstruction that was not resolved or required anti-infective treatment as judged by the investigator 14 days before the first study drug treatment; 5. Have a history of allogeneic organ transplantation. 6. Active or previously documented autoimmune or inflammatory disease, including inflammatory bowel disease (e.g., colitis or Crohn's disease), diverticulitis (other than diverticulosis), systemic lupus erythematosus, the sarcoidosis syndrome, or Wegener's syndrome (e.g., granulomatous vasculitis, Gray's disease, rheumatoid arthritis, hypophysitis, and uveitis). Exceptions to this criterion include patients with vitiligo or alopecia; Patients with hypothyroidism whose condition is stable after hormone replacement therapy (e.g., after Hashimoto's thyroiditis); Patients with any chronic skin disease that does not require systemic treatment; Patients who had not had active disease in the previous 5 years could be enrolled, but only after consultation with a study physician. Patients with celiac disease that can be controlled with diet alone. 7. Two consecutive urine routine tests showed urinary protein =++, and confirmed 24-hour urinary protein quantitation > 1.0 g; 8. Uncontrollable complications, including but not limited to: "Persistent or active infection (other than HBV or HCV described above), symptomatic congestive heart failure, uncontrolled diabetes mellitus, uncontrolled hypertension, unstable angina, uncontrolled cardiac arrhythmias, active ILD, severe chronic GI illness with diarrhea, or having a condition that could limit adherence to study requirements, result in a significantly increased risk of or impact on AE. Subjects provided written informed consent for psychiatric/social problem status. 9. Active infection, including pulmonary tuberculosis (clinical evaluation, including clinical history, physical examination, imaging findings, and locally performed testing for pulmonary tuberculosis), or human immunodeficiency virus (HIV 1/2 antibody positive). 10. Any toxic NCI Common Terminology Criteria for Adverse Events (CTCAE) = grade 2 that did not resolve after previous anticancer therapy, except for alopecia, vertigo, and laboratory values defined in the inclusion criteria. Patients with = grade 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician. 11. Allergic reactions or hypersensitivity reactions to any of the study drugs or any of their excipients are known. 12. Concomitant use of any chemotherapy, investigational drug, biologic therapy, or hormonal therapy for cancer treatment. Concomitant use of hormones for nontumor-related conditions (e.g., hormone-replacement therapy) is acceptable. 13. Radiotherapy (including palliative radiotherapy) was not allowed prior to the study, with the exception of postoperative adjuvant radiotherapy. 14. Vaccination with live attenuated vaccine within 30 days before the first dose of study drug. Note: If enrolled, patients were not allowed to receive live attenuated vaccine while receiving the study drug and for 30 days after the last dose. 15. Major surgical procedure (investigator-defined) within 28 days before the first dose of study drug. Minor surgery
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression free survival, PFS; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate, ORR;Disease control rate, DCR;Overall survival, OS; | — |
Countries
China
Contacts
Public ContactChen Xinni
General Hospital of Eastern Theater Command
Outcome results
None listed