{
    "info": {
        "nct_id": "NCT05220020",
        "official_title": "Prospective, Randomized Controlled, Single-center, Phase III Clinical Study of TACE Combined With Lenvatinib Versus TACE Sequential Lenvatinib in the Treatment of Intermediate/Advanced Liver Cancer",
        "inclusion_criteria": "* Provision of signed and dated, written informed consent form (ICF) and any locally required authorization obtained from the patient prior to any mandatory study specific procedures, sampling, and analyses.\n* Provision of signed and dated written genetic informed consent prior to optional collection of sample for genetic analysis.\n* Patients with BCLC stage C hepatocellular carcinoma confirmed by pathology or clinically diagnosed\n* Anticipated life expectancy ≥ 12 months\n* Eligible for TACE treatment, including BCLC-B, and BCLC-C only for Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1\n* No prior systemic therapy (including systemic investigational agents) for HCC, especially immunotherapy\n* Age ≥18 years and < 75 years at the time of screening.\n* Portal vein invasion or extrahepatic oligosaccharides were detected by baseline imaging. Oligosaccharides were defined as no more than two extrahepatic organs and no more than three tumors.\n* Portal vein thrombosis visible on baseline/eligibility imaging, patients with Vp1 and Vp2 are included\n* Patients who have previously undergone surgical resection, thermal ablation and other radical therapies for liver cancer may be enrolled. Prior TACE therapy must be used as part of the radical therapy (e.g. in combination with thermal ablation or surgery), but not as the sole form of previous treatment. These treatments need to be completed one month before enrollment.\n* Child-Pugh score class A to B7\n* No local antitumor therapy for hepatocellular carcinoma was received within 4 weeks prior to enrollment\n* No evidence of extrahepatic disease on any available imaging\n* No previous systemic antitumor therapy for hepatocellular carcinoma\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment\n* The expected survival time is no less than 3 months\n* BCLC Stage B: Patients with Intermediate HCC exceeding the \"up-to-seven\" criteria [i.e., the sum of tumor number (number) and maximum tumor diameter (cm) exceeds 7]\n* Patients with HBV infection, which is characterized by positive hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibodies (anti-HBcAb) with detectable HBV DNA (≥10 IU/ml or above the limit of detection per local lab standard), must be treated with antiviral therapy, as per institutional practice. HBV antiviral therapy must be initiated prior to randomization and patients must remain on antiviral therapy for the study duration and for 6 months after the last dose of study medication. Patients must show evidence HBV stabilization or signs of viral response (e.g., reduction HBV DNA levels) prior to starting IP. Patients who test positive for anti-hepatitis B core (HBc) with undetectable HBV DNA (<10 IU/ml or under the limit of detection per local lab standard) do not require anti-viral therapy prior to randomization. These subjects will be tested at every cycle to monitor HBV DNA levels and initiate antiviral therapy if HBV DNA is detected (≥10 IU/ml or above the limit of detection per local lab standard). HBV DNA detectable subjects must initiate and remain on antiviral therapy for the study duration and for 6 months after the last dose of study medication.\n* Patients with HCV infection must have management of this disease per local institutional practice throughout the study. HCV diagnosis is characterized by the presence of detectable HCV ribonucleic acid (RNA) or anti-HCV antibody upon enrollment.\n* At least 1 measurable intrahepatic lesion suitable for repeat assessments according to the following mRECIST criteria: （1）Liver lesions that show typical features of HCC on IV contrast-enhanced CT or MRI scans, ie, hypervascularity in the arterial phase with washout in the portal or the late venous phase；（2）Viable, non-necrotic portion (arterial phase IV contrast-enhancing) that can be accurately measured at baseline as ≥10 mm in the longest diameter.\n* Adequate organ and marrow function as defined below. Criteria \"a,\" \"b,\" \"c,\" and \"f\" may not be met with transfusions, infusions, or growth factor support administered within 14 days of starting the first dose.\n\nHemoglobin ≥9.0 g/dL、Absolute neutrophil count ≥1000/µL、Platelet count ≥50000/µL、Total bilirubin ≤2.0 × the upper limit of normal (ULN)、alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 × ULN、Albumin ≥2.8 g/dL、International normalized ratio ≤1.6、2+ proteinuria or less urine dipstick reading、Calculated creatinine clearance (CL) ≥30 mL/min as determined by Cockcroft-Gault (using actual body weight) or 24hour urine creatinine CL\n\nMales:\n\nCreatinine CL = Weight (kg) × (140 - Age) (mL/min) 72 × serum creatinine (mg/dL)\n\nFemales:\n\nCreatinine CL = Weight (kg) × (140 - Age) × 0.85 (mL/min) 72 × serum creatinine (mg/dL)\n\n* Must have a life expectancy of at least 12 weeks.\n* Body weight >30 kg\nHealthy volunteers allowed\nMust have minimum age of 18 Years\nMust have maximum age of 75 Years",
        "exclusion_criteria": "* Evidence of macrovascular invasion (MVI).\n* Evidence of extrahepatic spread (EHS)\n* Being a candidate for curative treatments (e.g. surgical resection, RFA or liver transplantation).\n* Any condition representing a contraindication to TACE as determined by the investigators(for example, the main portal vein obstruction without collateral vessels formed, etc.);\n* Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC;History of leptomeningeal disease;\n* Allergy to TACE process medications (such as contrast agents) or to Lenvatinib is known or suspected\n* There are obvious arteriovenous fistula or portal vein fistula in the liver.\n* Tumor invasion or oppression of the common bile duct, resulting in malignant obstructive jaundice;\n* Tumor volume of 70% or more of the liver;\n* Previous history of molecular targeted therapy, such as sorafenib, apatinib, etc.\n* Patients who had previously used systemic therapy (e.g., immunotherapy, targeted therapy) were excluded from the study\n* Severe heart conditions, such as congestive heart failure & GT; New York Heart Association (NYHA) Class II, active coronary artery disease (patients with myocardial infarction that occurred 6 months prior to enrollment), arrhythmias requiring treatment (other than beta-blockers, calcium antagonists, or digoxin); Uncontrolled hypertension (diastolic blood pressure not below 90mmHg even after treatment with 3 antihypertensive drugs;\n* Active clinical severe infection (> Level 2 NCI-CTCAE version 4.0);\n* Presence of active pulmonary tuberculosis or inability to exclude intrapulmonary lesions of old pulmonary tuberculosis.\n* Known tumors of the central nervous system, including brain metastases;\n* Clinically significant gastrointestinal bleeding within 30 days prior to enrollment;\n* Autoimmune disease (HIV);\n* Pregnant or breast-feeding patients;\n* Prior history of liver transplantation;\n* Any unstable condition or condition that may compromise the patient's safety and his/her compliance with the study.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Provision of signed and dated, written informed consent form (ICF) and any locally required authorization obtained from the patient prior to any mandatory study specific procedures, sampling, and analyses.",
            "criterions": [
                {
                    "exact_snippets": "Provision of signed and dated, written informed consent form (ICF)",
                    "criterion": "informed consent form",
                    "requirements": [
                        {
                            "requirement_type": "provision",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "signature",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "date",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "any locally required authorization obtained from the patient",
                    "criterion": "locally required authorization",
                    "requirements": [
                        {
                            "requirement_type": "obtained",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Provision of signed and dated written genetic informed consent prior to optional collection of sample for genetic analysis.",
            "criterions": [
                {
                    "exact_snippets": "Provision of signed and dated written genetic informed consent",
                    "criterion": "genetic informed consent",
                    "requirements": [
                        {
                            "requirement_type": "provision",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "signed",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "dated",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with BCLC stage C hepatocellular carcinoma confirmed by pathology or clinically diagnosed",
            "criterions": [
                {
                    "exact_snippets": "BCLC stage C hepatocellular carcinoma",
                    "criterion": "hepatocellular carcinoma",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "BCLC stage C"
                        }
                    ]
                },
                {
                    "exact_snippets": "confirmed by pathology or clinically diagnosed",
                    "criterion": "diagnosis confirmation",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": [
                                "pathology",
                                "clinical diagnosis"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Anticipated life expectancy ≥ 12 months",
            "criterions": [
                {
                    "exact_snippets": "Anticipated life expectancy ≥ 12 months",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Eligible for TACE treatment, including BCLC-B, and BCLC-C only for Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1",
            "criterions": [
                {
                    "exact_snippets": "Eligible for TACE treatment",
                    "criterion": "TACE treatment eligibility",
                    "requirements": [
                        {
                            "requirement_type": "eligibility",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "BCLC-B",
                    "criterion": "BCLC stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "B"
                        }
                    ]
                },
                {
                    "exact_snippets": "BCLC-C",
                    "criterion": "BCLC stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "C"
                        }
                    ]
                },
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1",
                    "criterion": "ECOG Performance Status",
                    "requirements": [
                        {
                            "requirement_type": "performance status",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 1,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* No prior systemic therapy (including systemic investigational agents) for HCC, especially immunotherapy",
            "criterions": [
                {
                    "exact_snippets": "No prior systemic therapy (including systemic investigational agents) for HCC",
                    "criterion": "prior systemic therapy for HCC",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "No prior ... especially immunotherapy",
                    "criterion": "prior immunotherapy for HCC",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Age ≥18 years and < 75 years at the time of screening.",
            "criterions": [
                {
                    "exact_snippets": "Age ≥18 years and < 75 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 18,
                                        "unit": "years"
                                    },
                                    {
                                        "operator": "<",
                                        "value": 75,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Portal vein invasion or extrahepatic oligosaccharides were detected by baseline imaging. Oligosaccharides were defined as no more than two extrahepatic organs and no more than three tumors.",
            "criterions": [
                {
                    "exact_snippets": "Portal vein invasion ... detected by baseline imaging.",
                    "criterion": "portal vein invasion",
                    "requirements": [
                        {
                            "requirement_type": "detection",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "extrahepatic oligosaccharides ... detected by baseline imaging.",
                    "criterion": "extrahepatic oligosaccharides",
                    "requirements": [
                        {
                            "requirement_type": "detection",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Oligosaccharides were defined as no more than two extrahepatic organs",
                    "criterion": "extrahepatic organs",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "no more than three tumors",
                    "criterion": "tumors",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 3,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Portal vein thrombosis visible on baseline/eligibility imaging, patients with Vp1 and Vp2 are included",
            "criterions": [
                {
                    "exact_snippets": "Portal vein thrombosis visible on baseline/eligibility imaging",
                    "criterion": "portal vein thrombosis",
                    "requirements": [
                        {
                            "requirement_type": "visibility",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "patients with Vp1 and Vp2 are included",
                    "criterion": "Vp1 and Vp2",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who have previously undergone surgical resection, thermal ablation and other radical therapies for liver cancer may be enrolled. Prior TACE therapy must be used as part of the radical therapy (e.g. in combination with thermal ablation or surgery), but not as the sole form of previous treatment. These treatments need to be completed one month before enrollment.",
            "criterions": [
                {
                    "exact_snippets": "Patients who have previously undergone surgical resection, thermal ablation and other radical therapies for liver cancer",
                    "criterion": "previous radical therapies for liver cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior TACE therapy must be used as part of the radical therapy ... but not as the sole form of previous treatment",
                    "criterion": "prior TACE therapy",
                    "requirements": [
                        {
                            "requirement_type": "combination with other therapies",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "These treatments need to be completed one month before enrollment",
                    "criterion": "completion of treatments",
                    "requirements": [
                        {
                            "requirement_type": "time before enrollment",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "month"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Child-Pugh score class A to B7",
            "criterions": [
                {
                    "exact_snippets": "Child-Pugh score class A to B7",
                    "criterion": "Child-Pugh score",
                    "requirements": [
                        {
                            "requirement_type": "class",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 5,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 7,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* No local antitumor therapy for hepatocellular carcinoma was received within 4 weeks prior to enrollment",
            "criterions": [
                {
                    "exact_snippets": "No local antitumor therapy for hepatocellular carcinoma was received within 4 weeks prior to enrollment",
                    "criterion": "local antitumor therapy for hepatocellular carcinoma",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* No evidence of extrahepatic disease on any available imaging",
            "criterions": [
                {
                    "exact_snippets": "No evidence of extrahepatic disease",
                    "criterion": "extrahepatic disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* No previous systemic antitumor therapy for hepatocellular carcinoma",
            "criterions": [
                {
                    "exact_snippets": "No previous systemic antitumor therapy for hepatocellular carcinoma",
                    "criterion": "previous systemic antitumor therapy for hepatocellular carcinoma",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": [
                                "0",
                                "1"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* The expected survival time is no less than 3 months",
            "criterions": [
                {
                    "exact_snippets": "expected survival time is no less than 3 months",
                    "criterion": "expected survival time",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* BCLC Stage B: Patients with Intermediate HCC exceeding the \"up-to-seven\" criteria [i.e., the sum of tumor number (number) and maximum tumor diameter (cm) exceeds 7]",
            "criterions": [
                {
                    "exact_snippets": "BCLC Stage B",
                    "criterion": "BCLC stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "B"
                        }
                    ]
                },
                {
                    "exact_snippets": "Intermediate HCC",
                    "criterion": "HCC stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "Intermediate"
                        }
                    ]
                },
                {
                    "exact_snippets": "exceeding the \"up-to-seven\" criteria [i.e., the sum of tumor number (number) and maximum tumor diameter (cm) exceeds 7]",
                    "criterion": "up-to-seven criteria",
                    "requirements": [
                        {
                            "requirement_type": "sum of tumor number and maximum tumor diameter",
                            "expected_value": {
                                "operator": ">",
                                "value": 7,
                                "unit": "N/A"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with HBV infection, which is characterized by positive hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibodies (anti-HBcAb) with detectable HBV DNA (≥10 IU/ml or above the limit of detection per local lab standard), must be treated with antiviral therapy, as per institutional practice. HBV antiviral therapy must be initiated prior to randomization and patients must remain on antiviral therapy for the study duration and for 6 months after the last dose of study medication. Patients must show evidence HBV stabilization or signs of viral response (e.g., reduction HBV DNA levels) prior to starting IP. Patients who test positive for anti-hepatitis B core (HBc) with undetectable HBV DNA (<10 IU/ml or under the limit of detection per local lab standard) do not require anti-viral therapy prior to randomization. These subjects will be tested at every cycle to monitor HBV DNA levels and initiate antiviral therapy if HBV DNA is detected (≥10 IU/ml or above the limit of detection per local lab standard). HBV DNA detectable subjects must initiate and remain on antiviral therapy for the study duration and for 6 months after the last dose of study medication.",
            "criterions": [
                {
                    "exact_snippets": "Patients with HBV infection, which is characterized by positive hepatitis B surface antigen (HBsAg)",
                    "criterion": "HBV infection",
                    "requirements": [
                        {
                            "requirement_type": "characterization",
                            "expected_value": "positive hepatitis B surface antigen (HBsAg)"
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients with HBV infection, which is characterized by ... hepatitis B core antibodies (anti-HBcAb)",
                    "criterion": "HBV infection",
                    "requirements": [
                        {
                            "requirement_type": "characterization",
                            "expected_value": "positive hepatitis B core antibodies (anti-HBcAb)"
                        }
                    ]
                },
                {
                    "exact_snippets": "detectable HBV DNA (≥10 IU/ml or above the limit of detection per local lab standard)",
                    "criterion": "HBV DNA",
                    "requirements": [
                        {
                            "requirement_type": "detectability",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 10,
                                        "unit": "IU/ml"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "HBV antiviral therapy must be initiated prior to randomization",
                    "criterion": "HBV antiviral therapy",
                    "requirements": [
                        {
                            "requirement_type": "initiation",
                            "expected_value": "prior to randomization"
                        }
                    ]
                },
                {
                    "exact_snippets": "patients must remain on antiviral therapy for the study duration and for 6 months after the last dose of study medication",
                    "criterion": "antiviral therapy duration",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "study duration and for 6 months after the last dose of study medication"
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients must show evidence HBV stabilization or signs of viral response (e.g., reduction HBV DNA levels) prior to starting IP",
                    "criterion": "HBV stabilization or viral response",
                    "requirements": [
                        {
                            "requirement_type": "evidence",
                            "expected_value": "prior to starting IP"
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients who test positive for anti-hepatitis B core (HBc) with undetectable HBV DNA (<10 IU/ml or under the limit of detection per local lab standard)",
                    "criterion": "anti-hepatitis B core (HBc)",
                    "requirements": [
                        {
                            "requirement_type": "test result",
                            "expected_value": "positive"
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients who test positive for anti-hepatitis B core (HBc) with undetectable HBV DNA (<10 IU/ml or under the limit of detection per local lab standard)",
                    "criterion": "HBV DNA",
                    "requirements": [
                        {
                            "requirement_type": "detectability",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<",
                                        "value": 10,
                                        "unit": "IU/ml"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "These subjects will be tested at every cycle to monitor HBV DNA levels",
                    "criterion": "HBV DNA monitoring",
                    "requirements": [
                        {
                            "requirement_type": "frequency",
                            "expected_value": "every cycle"
                        }
                    ]
                },
                {
                    "exact_snippets": "initiate antiviral therapy if HBV DNA is detected (≥10 IU/ml or above the limit of detection per local lab standard)",
                    "criterion": "antiviral therapy initiation",
                    "requirements": [
                        {
                            "requirement_type": "condition",
                            "expected_value": "HBV DNA detected (≥10 IU/ml or above the limit of detection per local lab standard)"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with HCV infection must have management of this disease per local institutional practice throughout the study. HCV diagnosis is characterized by the presence of detectable HCV ribonucleic acid (RNA) or anti-HCV antibody upon enrollment.",
            "criterions": [
                {
                    "exact_snippets": "Patients with HCV infection",
                    "criterion": "HCV infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "management of this disease per local institutional practice throughout the study",
                    "criterion": "HCV infection management",
                    "requirements": [
                        {
                            "requirement_type": "management",
                            "expected_value": "per local institutional practice throughout the study"
                        }
                    ]
                },
                {
                    "exact_snippets": "HCV diagnosis is characterized by the presence of detectable HCV ribonucleic acid (RNA)",
                    "criterion": "HCV ribonucleic acid (RNA)",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "HCV diagnosis is characterized by the presence of ... anti-HCV antibody upon enrollment",
                    "criterion": "anti-HCV antibody",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* At least 1 measurable intrahepatic lesion suitable for repeat assessments according to the following mRECIST criteria: （1）Liver lesions that show typical features of HCC on IV contrast-enhanced CT or MRI scans, ie, hypervascularity in the arterial phase with washout in the portal or the late venous phase；（2）Viable, non-necrotic portion (arterial phase IV contrast-enhancing) that can be accurately measured at baseline as ≥10 mm in the longest diameter.",
            "criterions": [
                {
                    "exact_snippets": "At least 1 measurable intrahepatic lesion",
                    "criterion": "intrahepatic lesion",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "lesion"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Liver lesions that show typical features of HCC on IV contrast-enhanced CT or MRI scans, ie, hypervascularity in the arterial phase with washout in the portal or the late venous phase",
                    "criterion": "liver lesions",
                    "requirements": [
                        {
                            "requirement_type": "features",
                            "expected_value": [
                                "hypervascularity in the arterial phase",
                                "washout in the portal or the late venous phase"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Viable, non-necrotic portion (arterial phase IV contrast-enhancing) that can be accurately measured at baseline as ≥10 mm in the longest diameter",
                    "criterion": "viable, non-necrotic portion",
                    "requirements": [
                        {
                            "requirement_type": "size",
                            "expected_value": {
                                "operator": ">=",
                                "value": 10,
                                "unit": "mm"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate organ and marrow function as defined below. Criteria \"a,\" \"b,\" \"c,\" and \"f\" may not be met with transfusions, infusions, or growth factor support administered within 14 days of starting the first dose.",
            "criterions": [
                {
                    "exact_snippets": "Adequate organ and marrow function",
                    "criterion": "organ and marrow function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Criteria \"a,\" \"b,\" \"c,\" and \"f\" may not be met with transfusions, infusions, or growth factor support administered within 14 days of starting the first dose.",
                    "criterion": "support methods",
                    "requirements": [
                        {
                            "requirement_type": "prohibition",
                            "expected_value": [
                                "transfusions",
                                "infusions",
                                "growth factor support"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "Hemoglobin ≥9.0 g/dL、Absolute neutrophil count ≥1000/µL、Platelet count ≥50000/µL、Total bilirubin ≤2.0 × the upper limit of normal (ULN)、alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 × ULN、Albumin ≥2.8 g/dL、International normalized ratio ≤1.6、2+ proteinuria or less urine dipstick reading、Calculated creatinine clearance (CL) ≥30 mL/min as determined by Cockcroft-Gault (using actual body weight) or 24hour urine creatinine CL",
            "criterions": [
                {
                    "exact_snippets": "Hemoglobin ≥9.0 g/dL",
                    "criterion": "hemoglobin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 9.0,
                                "unit": "g/dL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Absolute neutrophil count ≥1000/µL",
                    "criterion": "absolute neutrophil count",
                    "requirements": [
                        {
                            "requirement_type": "count",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1000,
                                "unit": "µL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Platelet count ≥50000/µL",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "count",
                            "expected_value": {
                                "operator": ">=",
                                "value": 50000,
                                "unit": "µL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Total bilirubin ≤2.0 × the upper limit of normal (ULN)",
                    "criterion": "total bilirubin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.0,
                                "unit": "× ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 × ULN",
                    "criterion": "alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 5,
                                "unit": "× ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Albumin ≥2.8 g/dL",
                    "criterion": "albumin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2.8,
                                "unit": "g/dL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "International normalized ratio ≤1.6",
                    "criterion": "international normalized ratio",
                    "requirements": [
                        {
                            "requirement_type": "ratio",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.6,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "2+ proteinuria or less urine dipstick reading",
                    "criterion": "proteinuria",
                    "requirements": [
                        {
                            "requirement_type": "urine dipstick reading",
                            "expected_value": "2+ or less"
                        }
                    ]
                },
                {
                    "exact_snippets": "Calculated creatinine clearance (CL) ≥30 mL/min as determined by Cockcroft-Gault (using actual body weight) or 24hour urine creatinine CL",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "clearance",
                            "expected_value": {
                                "operator": ">=",
                                "value": 30,
                                "unit": "mL/min"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Males:",
            "criterions": [
                {
                    "exact_snippets": "Males:",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "expected_value",
                            "expected_value": "male"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Creatinine CL = Weight (kg) × (140 - Age) (mL/min) 72 × serum creatinine (mg/dL)",
            "criterions": [
                {
                    "exact_snippets": "Creatinine CL = Weight (kg) × (140 - Age) (mL/min) 72 × serum creatinine (mg/dL)",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "calculation",
                            "expected_value": "Weight (kg) × (140 - Age) / (72 × serum creatinine (mg/dL))"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Females:",
            "criterions": [
                {
                    "exact_snippets": "Females:",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "expected_value",
                            "expected_value": "female"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Creatinine CL = Weight (kg) × (140 - Age) × 0.85 (mL/min) 72 × serum creatinine (mg/dL)",
            "criterions": [
                {
                    "exact_snippets": "Creatinine CL = Weight (kg) × (140 - Age) × 0.85 (mL/min) 72 × serum creatinine (mg/dL)",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "calculation",
                            "expected_value": "Weight (kg) × (140 - Age) × 0.85 (mL/min) / (72 × serum creatinine (mg/dL))"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Must have a life expectancy of at least 12 weeks.",
            "criterions": [
                {
                    "exact_snippets": "life expectancy of at least 12 weeks",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Body weight >30 kg",
            "criterions": [
                {
                    "exact_snippets": "Body weight >30 kg",
                    "criterion": "body weight",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">",
                                "value": 30,
                                "unit": "kg"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have minimum age of 18 Years",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 18 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have maximum age of 75 Years",
            "criterions": [
                {
                    "exact_snippets": "maximum age of 75 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "maximum",
                            "expected_value": {
                                "operator": "<=",
                                "value": 75,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "* Evidence of macrovascular invasion (MVI).",
            "criterions": [
                {
                    "exact_snippets": "Evidence of macrovascular invasion (MVI)",
                    "criterion": "macrovascular invasion",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Evidence of extrahepatic spread (EHS)",
            "criterions": [
                {
                    "exact_snippets": "Evidence of extrahepatic spread (EHS)",
                    "criterion": "extrahepatic spread",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Being a candidate for curative treatments (e.g. surgical resection, RFA or liver transplantation).",
            "criterions": [
                {
                    "exact_snippets": "Being a candidate for curative treatments (e.g. surgical resection, RFA or liver transplantation)",
                    "criterion": "candidate for curative treatments",
                    "requirements": [
                        {
                            "requirement_type": "eligibility",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any condition representing a contraindication to TACE as determined by the investigators(for example, the main portal vein obstruction without collateral vessels formed, etc.);",
            "criterions": [
                {
                    "exact_snippets": "Any condition representing a contraindication to TACE",
                    "criterion": "contraindication to TACE",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "main portal vein obstruction without collateral vessels formed",
                    "criterion": "main portal vein obstruction without collateral vessels",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC;History of leptomeningeal disease;",
            "criterions": [
                {
                    "exact_snippets": "Known fibrolamellar HCC",
                    "criterion": "fibrolamellar HCC",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "sarcomatoid HCC",
                    "criterion": "sarcomatoid HCC",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "mixed cholangiocarcinoma and HCC",
                    "criterion": "mixed cholangiocarcinoma and HCC",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "History of leptomeningeal disease",
                    "criterion": "leptomeningeal disease",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Allergy to TACE process medications (such as contrast agents) or to Lenvatinib is known or suspected",
            "criterions": [
                {
                    "exact_snippets": "Allergy to TACE process medications (such as contrast agents)",
                    "criterion": "allergy to TACE process medications",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Allergy ... to Lenvatinib is known or suspected",
                    "criterion": "allergy to Lenvatinib",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* There are obvious arteriovenous fistula or portal vein fistula in the liver.",
            "criterions": [
                {
                    "exact_snippets": "obvious arteriovenous fistula ... in the liver",
                    "criterion": "arteriovenous fistula in the liver",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "obvious ... portal vein fistula in the liver",
                    "criterion": "portal vein fistula in the liver",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Tumor invasion or oppression of the common bile duct, resulting in malignant obstructive jaundice;",
            "criterions": [
                {
                    "exact_snippets": "Tumor invasion or oppression of the common bile duct",
                    "criterion": "tumor invasion or oppression of the common bile duct",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "resulting in malignant obstructive jaundice",
                    "criterion": "malignant obstructive jaundice",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Tumor volume of 70% or more of the liver;",
            "criterions": [
                {
                    "exact_snippets": "Tumor volume of 70% or more of the liver",
                    "criterion": "tumor volume in liver",
                    "requirements": [
                        {
                            "requirement_type": "percentage",
                            "expected_value": {
                                "operator": ">=",
                                "value": 70,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Previous history of molecular targeted therapy, such as sorafenib, apatinib, etc.",
            "criterions": [
                {
                    "exact_snippets": "Previous history of molecular targeted therapy",
                    "criterion": "molecular targeted therapy",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who had previously used systemic therapy (e.g., immunotherapy, targeted therapy) were excluded from the study",
            "criterions": [
                {
                    "exact_snippets": "previously used systemic therapy (e.g., immunotherapy, targeted therapy)",
                    "criterion": "previous use of systemic therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Severe heart conditions, such as congestive heart failure & GT; New York Heart Association (NYHA) Class II, active coronary artery disease (patients with myocardial infarction that occurred 6 months prior to enrollment), arrhythmias requiring treatment (other than beta-blockers, calcium antagonists, or digoxin); Uncontrolled hypertension (diastolic blood pressure not below 90mmHg even after treatment with 3 antihypertensive drugs;",
            "criterions": [
                {
                    "exact_snippets": "Severe heart conditions, such as congestive heart failure & GT; New York Heart Association (NYHA) Class II",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">",
                                "value": 2,
                                "unit": "NYHA Class"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "active coronary artery disease (patients with myocardial infarction that occurred 6 months prior to enrollment)",
                    "criterion": "coronary artery disease",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        },
                        {
                            "requirement_type": "myocardial infarction history",
                            "expected_value": "6 months prior to enrollment"
                        }
                    ]
                },
                {
                    "exact_snippets": "arrhythmias requiring treatment (other than beta-blockers, calcium antagonists, or digoxin)",
                    "criterion": "arrhythmias",
                    "requirements": [
                        {
                            "requirement_type": "treatment requirement",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "treatment exclusion",
                            "expected_value": [
                                "beta-blockers",
                                "calcium antagonists",
                                "digoxin"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Uncontrolled hypertension (diastolic blood pressure not below 90mmHg even after treatment with 3 antihypertensive drugs",
                    "criterion": "hypertension",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": "uncontrolled"
                        },
                        {
                            "requirement_type": "diastolic blood pressure",
                            "expected_value": {
                                "operator": ">=",
                                "value": 90,
                                "unit": "mmHg"
                            }
                        },
                        {
                            "requirement_type": "treatment",
                            "expected_value": "3 antihypertensive drugs"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Active clinical severe infection (> Level 2 NCI-CTCAE version 4.0);",
            "criterions": [
                {
                    "exact_snippets": "Active clinical severe infection (> Level 2 NCI-CTCAE version 4.0)",
                    "criterion": "clinical severe infection",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">",
                                "value": 2,
                                "unit": "NCI-CTCAE version 4.0"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Presence of active pulmonary tuberculosis or inability to exclude intrapulmonary lesions of old pulmonary tuberculosis.",
            "criterions": [
                {
                    "exact_snippets": "Presence of active pulmonary tuberculosis",
                    "criterion": "active pulmonary tuberculosis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "inability to exclude intrapulmonary lesions of old pulmonary tuberculosis",
                    "criterion": "intrapulmonary lesions of old pulmonary tuberculosis",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Known tumors of the central nervous system, including brain metastases;",
            "criterions": [
                {
                    "exact_snippets": "Known tumors of the central nervous system",
                    "criterion": "tumors of the central nervous system",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "brain metastases",
                    "criterion": "brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Clinically significant gastrointestinal bleeding within 30 days prior to enrollment;",
            "criterions": [
                {
                    "exact_snippets": "Clinically significant gastrointestinal bleeding within 30 days prior to enrollment",
                    "criterion": "gastrointestinal bleeding",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "clinically significant"
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 30 days prior to enrollment"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Autoimmune disease (HIV);",
            "criterions": [
                {
                    "exact_snippets": "Autoimmune disease (HIV)",
                    "criterion": "autoimmune disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Autoimmune disease (HIV)",
                    "criterion": "HIV",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Pregnant or breast-feeding patients;",
            "criterions": [
                {
                    "exact_snippets": "Pregnant",
                    "criterion": "pregnancy status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "breast-feeding",
                    "criterion": "breastfeeding status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prior history of liver transplantation;",
            "criterions": [
                {
                    "exact_snippets": "Prior history of liver transplantation",
                    "criterion": "liver transplantation",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any unstable condition or condition that may compromise the patient's safety and his/her compliance with the study.",
            "criterions": [
                {
                    "exact_snippets": "Any unstable condition",
                    "criterion": "unstable condition",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "condition that may compromise the patient's safety",
                    "criterion": "condition compromising safety",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "condition that may compromise ... compliance with the study",
                    "criterion": "condition compromising compliance",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}