cTACE Plus Sintilimab for Unresectable Intermediate-stage HCC With Beyond Up-to-seven Criteria

Inclusion criteria

• Age ≥20 and ≤75 years old
• Clinically diagnosed or pathologically confirmed advanced hepatocellular carcinoma. ( Fibrolamellae and mixed hepatocellular/cholangiocarcinoma subtypes are not included)
• CNLC stage IIa/IIb or BCLC stage B, not eligible for resection or local ablation, beyond up-to-seven criteria (hepatocellular carcinomas with seven as the sum of the size of the largest tumor [in cm] and the number of tumors)
• Newly diagnosed or recurrent more than half a year after radical surgery
• No prior TACE treatment,
• Child-Pugh A, ECOG PS: 0-1
• Patients with chronic HBV infection must have HBV DNA viral load < 500 IU/mL at screening. In addition, they must be on antiviral therapy per regional standard of care guidelines prior to initiation of study therapy.
• At least one measurable site of disease as defined by modified RECIST (mRECIST) and RECICL criteria with spiral CT scan or MRI.
• Life expectancy of at least 3 months.
• Adequate blood count, liver-enzymes, and renal function: Haemoglobin ≥ 8.5 g/dL, absolute neutrophil count ≥ 1,500/L, platelets ≥70 x103/L; Total bilirubin ≤ 3x upper normal limit; Aspartate Aminotransferase (SGOT), Alanine aminotransferase (SGPT) ≤ 5 x upper normal limit (ULN); International normalized ratio (INR) ≤1.25; Albumin ≥ 31 g/dL; Serum Creatinine ≤ 1.5 x institutional ULN or creatinine clearance (CrCl) ≥ 30 mL/min (if using the Cockcroft-Gault formula )
• Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment, adherence to contraceptive measures, scheduled visits and examinations including follow up.
• Normal T3 and T4. (T3 and T4 controlled in the normal range through treatment is also eligible.)
• Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial.

Exclusion criteria

• Diffuse HCC or presence of vascular invasion or extrahepatic spread.
• The patient suffered from other malignant tumors in the past 3 years or at the same time (except for cured skin basal cell carcinoma and cervical carcinoma in situ).
• Known history of hepatic encephalopathy within 6 months
• Known history of cardiac disease within 12 months before the first dose of study drug.
• Clinically significant hemoptysis or tumor bleeding of any reason within 2 weeks before the first dose of study drug.
• Severe unhealed wounds, ulcers, or fractures
• Prior systemic anti-cancer therapy.
• Prior treatment with TACE.
• Suffer from high blood pressure and cannot be well controlled by antihypertensive drugs (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg)
• Any active autoimmune disease or a history of autoimmune disease.
• Major surgery within 4 weeks of starting the study treatment OR subjects who have not recovered from effects of major surgery.
• History of allogeneic tissue/solid organ transplant.
• Urine routine test showed urine protein ≥ ++ and confirmed 24-hour urine protein content> 1.0 g.
• Prior therapy with an anti-Programmed cell death protein 1 (anti-PD-1), anti-PD-L1, anti-Programmed cell death-ligand 2 (anti-PD-L2), anti-CD137 (4-1BB ligand, a member of the Tumor Necrosis Factor Receptor (TNFR) family), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
• Female patients who are pregnant, breast-feeding.