| Eligibility |
Inclusion Criteria:
1. Written informed consent should be signed before implementing any trial-related
procedures
2. ECOG PS scores 0-1
3. Histologically/cytologically confirmed HCC or cirrhosis meeting the clinical
diagnostic criteria of HCC by American Association for the Study of Liver Diseases
(AASLD)
4. Barcelona Clinic Liver Cancer (BCLC) stage C
5. Newly diagnosed HHC patients without any previous treatment for the tumor
6. Child Pugh score of = 7.
7. Estimated survival > 12 weeks
8. At least one measurable lesion according to RECIST V1.1
9. Sufficient organ and bone marrow functions
Exclusion Criteria:
1. Histologically/cytologically confirmed fibrolamellar hepatocellular carcinoma,
sarcomatoid hepatocellular carcinoma, and cholangiocarcinoma.
2. History of hepatic encephalopathy or liver transplantation.
3. Symptomatic pleural effusion, ascites, and pericardial effusion that require drainage.
4. Acute or chronic active hepatitis B or C infection; hepatitis B virus (HBV) DNA > 2000
IU/mL or 104 copies/mL; hepatitis C virus (HCV) RNA > 103 copies/mL; hepatitis B
surface antigen (HbsAg) and anti HCV antibody positive concurrently.
5. Presence of metastasis to the central nervous system.
6. Presence of bleeding events from esophageal or gastric varices caused by portal
hypertension within the past 6 months. Presence of known severe (G3) varicose veins in
endoscopy within 3 months before the first dose. Evidence of portal hypertension
(including the finding of splenomegaly in imaging studies) with a high risk of
bleeding assessed by the investigator.
7. Presence of any life-threatening bleeding events within the past 3 months, including
the need for transfusion, surgery or local treatment, and continuous medication
therapy.
8. Any arterial/venous thromboembolic events within 6 months, including myocardial
infarction, unstable angina, cerebrovascular accident or transient cerebral ischemic
attack, pulmonary embolism, deep vein thrombosis, or any other history of serious
thromboembolism. Presence of implantable venous port or catheter derived thrombosis,
or superficial venous thrombosis, barring stable thrombosis following the conventional
anticoagulation treatment. Prophylactic use of low dose low molecular weight heparin
(e.g., enoxaparin 40 mg/day) is permitted.
9. Involvement of both the main portal vein and the left and right branches by portal
vein tumor thrombus, or of both the main trunk and the superior mesenteric vein
concurrently. Presence of tumor thrombus of inferior vena cava.
10. A 10-day consecutive dosing of aspirin (> 325 mg/day) or other drugs, e.g.,
dipyridamole and clopidogrel, known to inhibit the platelet function within 2 weeks
before the first dose.
11. Uncontrolled hypertension (systolic greater than 140 mmHg or diastolic greater than 90
mmHg) after the optimal medical treatment, history of hypertensive crisis or
hypertensive encephalopathy.
12. Toxicity (excluding alopecia, events not clinically significant, and asymptomatic
laboratory abnormalities) caused by previous therapy that has not yet resolved to
grade 0 or 1 (National Cancer Institute Common Terminology Criteria for Adverse Events
V5.0 (NCI CTCAE V5.0)) before the first dose of study drugs.
13. Symptomatic congestive cardiac failure (NYHA Class II IV). Symptomatic or poorly
controlled arrhythmia. History of congenital long QT syndrome or corrected QTc > 500
ms (calculated using Fridericia formula) during screening.
14. Serious hemorrhagic tendency or coagulopathy, or currently receiving thrombolytic
therapy.
15. History of gastrointestinal perforation and/or fistula, history of bowel obstruction
(including incomplete bowel obstruction requiring parenteral nutrition), extensive
bowel resection (partial colectomy or extensive small bowel resection accompanied with
chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea within the
past 6 months.
16. Receipt of immunosuppressants within 4 weeks before the first dose, excluding local
glucocorticoids administered by nasal, inhaled, or other topical routes, or systemic
glucocorticoids of physiological doses (no more than 10 mg/day of prednisone or
equivalents), while the temporary use of glucocorticoids for preventing allergies or
treating dyspneic symptoms of such diseases as asthma and chronic obstructive
pulmonary disease is permitted.
17. Receipt of a live attenuated vaccine within 4 weeks before the first dose or planned
to receive a live attenuated vaccine during the study.
18. Receipt of major surgery (craniotomy, thoracotomy, or laparotomy) within 4 weeks
before the first dose or having unhealed wounds, ulcers, or fractures. Receipt of
tissue biopsy or other minor surgeries within 7 days before the first dose, barring
venipuncture and catheterization for intravenous infusion.
19. Receipt of local treatment for liver cancer within 4 weeks before the first dose.
Receipt of systemic treatment with traditional Chinese medicines with cancer
indications or immunomodulators (including thymosin, interferon, and interleukin,
barring local use for controlling pleural fluid or ascites) within 2 weeks before the
first dose.
20. Uncontrolled/uncorrectable metabolic disorders, other non malignant organ diseases,
systemic diseases, or cancer related secondary diseases with the potential to cause a
relatively high medical risk and/or survival evaluation uncertainties unsuitable for
subject enrollment as judged by the investigator; other circumstances unsuitable for
subject enrollment as judged by the investigator.
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