| Eligibility |
Inclusion Criteria:
1. Voluntarily join the study and sign the informed consent;
2. Age 18 ~ 80 years old (including 80 years old), male and female;
3. Patients with hepatohcellular carcinoma diagnosed clinically or confirmed by histology
/ cytology according to the code for diagnosis and treatment of primary liver cancer
(2019 Edition);
4. Patients with unresectable or metastatic hepatocellular carcinoma;
5. No systematic treatment. If receiving adjuvant chemotherapy after local treatment more
than 12 months, and patients with disease progression or metastasis can also be
included in the group;
6. The end time of the last intervention, radiotherapy and ablation should be > 4 weeks;
7. Patients who underwent hepatectomy in the past should be R0 resection, and the tumor
recurrence should be more than 24 months after operation;
8. At least one assessable lesion (RECIST 1.1 criteria);
9. Expected survival time = 3 months;
10. ECOG 0 ~ 1;
11. Child Pugh = 7;
12. Be able to cooperate to observe adverse events;
13. Major organs are functioning normally.
1. Hemoglobin = 90 g / L;
2. ANC = 1.5 × 109/L;
3. Platelet count = 75 × 109/L;
4. Albumin = 28 g / L;
5. Total bilirubin = 2 × ULN;
6. AST, ALT = 5 × ULN;
7. ALP = 5 × ULN;
8. Creatinine = 1.5 × ULN;
9. INR or PT = 1.5 × ULN; J) APTT = 1.5 × ULN?
Exclusion Criteria:
1. Fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma,
cholangiocarcinoma and other components confirmed by histology / cytology in the past;
2. Have a history of malignancy other than hepatocellular carcinoma unless the following
criteria are met:
A) The patient has received possible curative treatment and there is no evidence of
the disease within 5 years; B) Successful resection of basal cell carcinoma of skin,
squamous cell carcinoma of skin, superficial bladder carcinoma, carcinoma in situ of
cervix and other cancers in situ
3. Diffuse tumor lesions;
4. Tumor vascular invasion occurs in one or more of the following situations:
1. Involving superior mesenteric vein;
2. Involving inferior vena cava;
5. History of hepatic encephalopathy, hepatorenal syndrome, or history of liver
transplantation;
6. Pleural effusion, ascites and pericardial effusion with clinical symptoms requiring
drainage;
7. Central system metastasis;
8. Previous history of severe mental illness;
9. Have a disease that affects absorption, distribution, metabolism, or clearance of the
drug under study (such as severe vomiting, chronic diarrhea, intestinal obstruction,
absorption disorder, etc.);
10. Previous allogeneic stem cell or parenchymal organ transplantation;
11. Previously received targeted therapy of anti VEGF and / or signal pathways such as
VEGFR, RAF and MEK, such as sorafenib, renvatinib and regofinib, or immunomodulator
therapy such as anti-PD-1, anti-PD-L1 and anti-CTLA-4;
12. Patients who have received other anti-tumor systemic treatment in the past, including
traditional Chinese medicine with anti-tumor indications less than 2 weeks before the
administration of this study, or the adverse events caused by previous treatment have
not recovered to = CTCAE level 1; The toxicity of previous anti-tumor treatment did
not include grade 1 / 2 neurotoxicity and hair loss caused by oxaliplatin;
13. Taking drugs that may prolong QTc and / or induce tip twist transition ventricular
tachycardia (TDP) or drugs that affect metabolism at the same time;
14. Previous or current congenital or acquired immunodeficiency disease;
15. Active or previously documented autoimmune disease or inflammatory disease.
16. Previous allogeneic stem cell or parenchymal organ transplantation;
17. Systemic immunosuppressive drugs were used within 2 weeks before enrollment, or
systemic immunosuppressive drugs expect to be needed during the study, except for the
following:
d) Intranasal, inhalation, topical or local injection (such as intra-articular
injection) of corticosteroids; e) Systemic corticosteroids with dose not exceeding 10
mg / day, prednisone or other effects; f) Prophylactic use of corticosteroids for
hypersensitivity;
18. Allergy to Donafenib or similar drugs, or history of hypersensitivity to chimeric or
humanized antibodies or fusion proteins, or allergy to the excipients of the study
drugs;
19. Have active bleeding or abnormal coagulation function, have bleeding tendency or are
receiving thrombolytic, anticoagulant or antiplatelet therapy;
20. Thrombosis or thromboembolism events occurred in the past 6 months, such as stroke and
/ or transient ischemic attack, deep vein thrombosis, pulmonary embolism, etc;
21. Bleeding events of esophageal or gastric varices caused by portal hypertension in the
past 6 months, or any life-threatening bleeding events in 3 months;
22. Cardiovascular diseases with significant clinical significance, including but not
limited to acute myocardial infarction, severe / unstable angina or coronary artery
bypass grafting in the past 6 months, congestive heart failure (NYHA grade > 2),
arrhythmias poorly controlled or requiring pacemaker treatment, and hypertension not
controlled by drugs (systolic blood pressure = 140 mmHg and / or diastolic blood
pressure = 90 mmHg);
23. Other significant clinical and laboratory abnormalities considered by the investigator
to affect safety;
24. Severe infections in the active stage or under clinical control; Active infections
include:
1. HIV1/2 is positive.
2. HBsAg positive or HBV DNA > 2000iu/ml and abnormal liver function;
3. HCV antibody positive or HCV RNA = 103 copies/ml and abnormal liver function;
4. Active tuberculosis;
5. Other uncontrollable active infections (CTCAE V5.0 > grade 2);
25. Not recovered from the operation, such as unhealed incision or serious postoperative
complications;
26. Pregnant or lactating women, and women or men with fertility are unwilling or unable
to take effective contraceptive measures.
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