Hepatocellular carcinoma
Conditions
Interventions
First-line treatment group:combination of anti-pd-1 / pd-l1 antibody and Donafenib
Second-line treatment group:combination of anti-pd-1 / pd-l1 antibody and Donafenib
Sponsors
Department of Hepatobiliary Surgery Chinese PLA General Hospital & Medical School
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Voluntarily join the group and sign a written informed consent; 2. Aged 18~75 years(including 75 years old), male or female; 3. Patients with hepatocellular carcinoma who were clinically diagnosed or diagnosed by histopathology/cytology in accordance with the "Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2019 Edition)"; 4. Patients with inoperable or metastatic hepatocellular carcinoma; 5. First-line treatment cohort: patients who have not received systemic therapy; second-line treatment cohort: patients who progress or are intolerant after first-line systemic therapy; 6. If they have received adjuvant chemotherapy after local treatment, the end of chemotherapy should be more than 12 months, and patients with disease progression or metastasis can also be enrolled; surgical treatment> 3 months, the last intervention, radiotherapy and ablation therapy and systemic drug therapy end time > 4 weeks; 7. There is at least one measurable lesion; (1) Definition of measurable lesions: non-lymphatic lesions with the longest single diameter >=10mm, or lymph node lesions with the shortest diameter >= 15mm. (2) Lesions after previous interventional, radiotherapy or ablation therapy that have clearly progressed according to RECIST1.1 criteria and whose longest diameter is >=10 mm can also be used as measurable target lesions. 8. Expected survival time >= 3 months; 9. Eastern Cooperative Oncology Group (ECOG) physical status (PS) score of 0 to 1; 10. Child-Pugh score is A; 11. Can cooperate to observe adverse events and curative effects; 12. The function of major organs is normal, that is, the following criteria are met: routine blood examination (no blood transfusion and no G-CSF use within 14 days before screening): hemoglobin >= 90 g/L; absolute neutrophil count (ANC) >= 1.5x 10^9/L; platelet count >= 75x10^9/L; blood biochemical examination (albumin was not used within 14 days before screening): albumin >= 28 g/L; total bilirubin <=2xUpper limit of normal (ULN); aspartate aminotransferase (AST), alanine aminotransferase (ALT)<= 5xULN; alkaline phosphatase (ALP)<= 5xULN; creatinine<=1.5xULN; coagulation function: International normalized ratio (INR) or prothrombin time (PT) <= 1.5xULN; activated partial thromboplastin time (APTT) <= 1.5xULN.
Exclusion criteria
Exclusion criteria: 1. A history of malignancy other than hepatocellular carcinoma, unless the following criteria are met: (1) The patient has received possible curative treatment and there is no evidence of the disease within 5 years; (2) Skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ and other carcinomas in situ who have successfully undergone resection; 2. Have a history of hepatic encephalopathy, hepatorenal syndrome, or a history of liver transplantation; 3. Pleural effusion, ascites, and pericardial effusion with clinical symptoms requiring drainage; 4. There is central system transfer; 5. A history of serious mental illness; 6. Suffering from diseases that affect the absorption, distribution, metabolism or clearance of the study drug (such as severe vomiting, chronic diarrhea, intestinal obstruction, malabsorption, etc.); Previous or concomitant medications/treatments: 7. Previously received allogeneic stem cell or solid organ transplantation; 8. Concomitant use of drugs that may prolong QTc and/or induce torsades de pointes (Tdp) or drugs that affect drug metabolism; 9. Active or previously documented autoimmune disease or inflammatory disease (including but not limited to: autoimmune hepatitis, interstitial pneumonia, inflammatory bowel disease, systemic lupus erythematosus, vasculitis, uveitis, Hypophysitis, hyperthyroidism or hypothyroidism, asthma requiring bronchodilator treatment, etc.), patients with vitiligo or asthma that has been completely resolved in childhood, without any intervention in adulthood can be included; 10. Previously received allogeneic stem cell or solid organ transplantation; 11. Previous treatment with Donafenib; 12. Systemic immunosuppressive drug treatment has been used within 2 weeks before enrollment, or systemic immunosuppressive drug treatment is expected to be required during the study period, except for the following cases: (1) Intranasal, inhaled, topical or local injection (such as intra-articular injection) corticosteroids; (2) The dose does not exceed 10 mg/day of prednisone or other equivalent systemic corticosteroids; (3) Prophylactic use of corticosteroids for hypersensitivity reactions; 13. The patient is known or suspected to have a history of allergy to Donafenib or similar drugs, or a history of hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins, or allergic to the excipients of the study drug; 14. Active bleeding or abnormal coagulation function, with bleeding tendency or receiving thrombolysis, anticoagulation or antiplatelet therapy; 15. Having experienced thrombosis or thromboembolic events in the past 6 months, such as stroke and/or transient ischemic attack, deep vein thrombosis, pulmonary embolism, etc.; 16. Hemorrhagic events of esophageal or gastric varices caused by portal hypertension within the past 6 months, or any life-threatening bleeding events within 3 months; 17. Cardiovascular disease with significant clinical significance, including but not limited to acute myocardial infarction, severe/unstable angina pectoris or coronary artery bypass surgery within the past 6 months, congestive heart failure (NYHA classification of the New York Heart Association > grade 2 ), poorly controlled arrhythmias that require pacemaker therapy, and uncontrolled hypertension (systolic blood pressure >= 140 mmHg and/or diastolic blood pressure >= 90 mmHg); 18. Other significant clinical and
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| objective response rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| disease control rate;duration of relief;progression-free survival;overall survival;Survival rates at 6, 9, 12, and 18 months;Alpha-fetoprotein level;adverse event;serious adverse event; | — |
Countries
China
Contacts
Public ContactLiu Rong
Department of Hepatobiliary Surgery, Chinese PLA General Hospital & Medical School
Outcome results
None listed