{
    "info": {
        "nct_id": "NCT03952065",
        "official_title": "A Phase II/III Randomized Trial of Comparison of Survival Benefit of Administration of PD1/PDL1/CTLA4 Inhibitors or Their Combinations Via Neck Artery or Intratumor Versus Vein Infusion for Immunotherapy of HNC",
        "inclusion_criteria": "1. Cytohistological confirmation is required for diagnosis of HNC.\n2. Signed informed consent before recruiting.\n3. Age between 18 to 80 years with estimated survival over 3 months.\n4. ECOG score < 2\n5. Tolerable coagulation function or reversible coagulation disorders\n6. Laboratory examination test within 7 days prior to procedure: WBC≥3.0×10E9/L; Hb≥90g/L； PLT ≥50×10E9/L；INR < 2.3 or PT < 6 seconds above control；Cr ≤ 145.5 umul/L；Albumin > 28 g/L；Total bilirubin < 51 μmol/L\n7. At least one tumor lesion meeting measurable disease criteria as determined by RECIST v1.1.\n8. Patients with advanced HNC which would not be suitable for treatment with loco-regional therapies or have progressed following locoregional therapy such as surgical resection and other treatment.\n9. Birth control.\n10. Willing and able to comply with scheduled visits, treatment plan and laboratory tests.\nHealthy volunteers allowed\nMust have minimum age of 18 Years\nMust have maximum age of 80 Years",
        "exclusion_criteria": "1. Patients participated in other clinical trials of equipment or drugs (signed informed consent) within 4 weeks;\n2. Any serious accompanying disease, which is expected to have an unknown, impact on the prognosis, include heart disease, inadequately controlled diabetes and psychiatric disorders;\n3. Patients accompanied with other tumors or past medical history of malignancy;\n4. Pregnant or lactating patients, all patients participating in this trial must adopt appropriate birth control measures during treatment;\n5. Patients have poor compliance.\n\n   Any contraindications for neck artery infusion procedure:\n\n   A. Impaired clotting test (platelet count < 60000/mm3, prothrombin activity < 50%).\n\n   B. Renal failure / insufficiency requiring hemo-or peritoneal dialysis. C. Known severe atheromatosis. D. Known uncontrolled blood hypertension (> 160/100 mm/Hg).\n6. Allergic to adriamycin chemotherapy drugs，contrast agent or lipiodol;\n7. Any agents which could affect the absorption or pharmacokinetics of the study drugs\n8. Subjects unable to suffer the discomfort of the artery infusion procedure",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Cytohistological confirmation is required for diagnosis of HNC.",
            "criterions": [
                {
                    "exact_snippets": "Cytohistological confirmation is required for diagnosis of HNC.",
                    "criterion": "cytohistological confirmation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "diagnosis of HNC",
                    "criterion": "HNC diagnosis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Signed informed consent before recruiting.",
            "criterions": [
                {
                    "exact_snippets": "Signed informed consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "signed",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Age between 18 to 80 years with estimated survival over 3 months.",
            "criterions": [
                {
                    "exact_snippets": "Age between 18 to 80 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 18,
                                        "unit": "years"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 80,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "estimated survival over 3 months",
                    "criterion": "estimated survival",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. ECOG score < 2",
            "criterions": [
                {
                    "exact_snippets": "ECOG score < 2",
                    "criterion": "ECOG score",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<",
                                "value": 2,
                                "unit": "N/A"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Tolerable coagulation function or reversible coagulation disorders",
            "criterions": [
                {
                    "exact_snippets": "Tolerable coagulation function",
                    "criterion": "coagulation function",
                    "requirements": [
                        {
                            "requirement_type": "tolerance",
                            "expected_value": "tolerable"
                        }
                    ]
                },
                {
                    "exact_snippets": "reversible coagulation disorders",
                    "criterion": "coagulation disorders",
                    "requirements": [
                        {
                            "requirement_type": "reversibility",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Laboratory examination test within 7 days prior to procedure: WBC≥3.0×10E9/L; Hb≥90g/L； PLT ≥50×10E9/L；INR < 2.3 or PT < 6 seconds above control；Cr ≤ 145.5 umul/L；Albumin > 28 g/L；Total bilirubin < 51 μmol/L",
            "criterions": [
                {
                    "exact_snippets": "WBC≥3.0×10E9/L",
                    "criterion": "WBC",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3.0,
                                "unit": "×10E9/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Hb≥90g/L",
                    "criterion": "Hb",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 90,
                                "unit": "g/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "PLT ≥50×10E9/L",
                    "criterion": "PLT",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 50,
                                "unit": "×10E9/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "INR < 2.3",
                    "criterion": "INR",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<",
                                "value": 2.3,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "PT < 6 seconds above control",
                    "criterion": "PT",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<",
                                "value": 6,
                                "unit": "seconds above control"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Cr ≤ 145.5 umul/L",
                    "criterion": "Cr",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 145.5,
                                "unit": "umul/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Albumin > 28 g/L",
                    "criterion": "Albumin",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">",
                                "value": 28,
                                "unit": "g/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Total bilirubin < 51 μmol/L",
                    "criterion": "Total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<",
                                "value": 51,
                                "unit": "μmol/L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. At least one tumor lesion meeting measurable disease criteria as determined by RECIST v1.1.",
            "criterions": [
                {
                    "exact_snippets": "At least one tumor lesion meeting measurable disease criteria as determined by RECIST v1.1.",
                    "criterion": "tumor lesion",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "lesion"
                            }
                        },
                        {
                            "requirement_type": "measurable disease criteria",
                            "expected_value": "RECIST v1.1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Patients with advanced HNC which would not be suitable for treatment with loco-regional therapies or have progressed following locoregional therapy such as surgical resection and other treatment.",
            "criterions": [
                {
                    "exact_snippets": "advanced HNC",
                    "criterion": "HNC (head and neck cancer)",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "advanced"
                        }
                    ]
                },
                {
                    "exact_snippets": "not be suitable for treatment with loco-regional therapies",
                    "criterion": "suitability for loco-regional therapies",
                    "requirements": [
                        {
                            "requirement_type": "suitability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "have progressed following locoregional therapy",
                    "criterion": "progression after locoregional therapy",
                    "requirements": [
                        {
                            "requirement_type": "progression",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Birth control.",
            "criterions": [
                {
                    "exact_snippets": "Birth control",
                    "criterion": "birth control",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Willing and able to comply with scheduled visits, treatment plan and laboratory tests.",
            "criterions": [
                {
                    "exact_snippets": "Willing and able to comply with scheduled visits",
                    "criterion": "compliance with scheduled visits",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Willing and able to comply with ... treatment plan",
                    "criterion": "compliance with treatment plan",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Willing and able to comply with ... laboratory tests",
                    "criterion": "compliance with laboratory tests",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "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 80 Years",
            "criterions": [
                {
                    "exact_snippets": "maximum age of 80 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "maximum",
                            "expected_value": {
                                "operator": "<=",
                                "value": 80,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "1. Patients participated in other clinical trials of equipment or drugs (signed informed consent) within 4 weeks;",
            "criterions": [
                {
                    "exact_snippets": "Patients participated in other clinical trials of equipment or drugs (signed informed consent) within 4 weeks",
                    "criterion": "participation in other clinical trials",
                    "requirements": [
                        {
                            "requirement_type": "time since participation",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Any serious accompanying disease, which is expected to have an unknown, impact on the prognosis, include heart disease, inadequately controlled diabetes and psychiatric disorders;",
            "criterions": [
                {
                    "exact_snippets": "serious accompanying disease",
                    "criterion": "serious accompanying disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "heart disease",
                    "criterion": "heart disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "inadequately controlled diabetes",
                    "criterion": "inadequately controlled diabetes",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "psychiatric disorders",
                    "criterion": "psychiatric disorders",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Patients accompanied with other tumors or past medical history of malignancy;",
            "criterions": [
                {
                    "exact_snippets": "Patients accompanied with other tumors",
                    "criterion": "other tumors",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "past medical history of malignancy",
                    "criterion": "past medical history of malignancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Pregnant or lactating patients, all patients participating in this trial must adopt appropriate birth control measures during treatment;",
            "criterions": [
                {
                    "exact_snippets": "Pregnant or lactating patients",
                    "criterion": "pregnancy status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "not pregnant or lactating"
                        }
                    ]
                },
                {
                    "exact_snippets": "all patients participating in this trial must adopt appropriate birth control measures during treatment",
                    "criterion": "birth control measures",
                    "requirements": [
                        {
                            "requirement_type": "adoption",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Patients have poor compliance.",
            "criterions": [
                {
                    "exact_snippets": "Patients have poor compliance.",
                    "criterion": "compliance",
                    "requirements": [
                        {
                            "requirement_type": "quality",
                            "expected_value": "poor"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Any contraindications for neck artery infusion procedure:",
            "criterions": [
                {
                    "exact_snippets": "contraindications for neck artery infusion procedure",
                    "criterion": "neck artery infusion procedure",
                    "requirements": [
                        {
                            "requirement_type": "contraindications",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "A. Impaired clotting test (platelet count < 60000/mm3, prothrombin activity < 50%).",
            "criterions": [
                {
                    "exact_snippets": "platelet count < 60000/mm3",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<",
                                "value": 60000,
                                "unit": "mm3"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "prothrombin activity < 50%",
                    "criterion": "prothrombin activity",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<",
                                "value": 50,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "B. Renal failure / insufficiency requiring hemo-or peritoneal dialysis. C. Known severe atheromatosis. D. Known uncontrolled blood hypertension (> 160/100 mm/Hg).",
            "criterions": [
                {
                    "exact_snippets": "Renal failure / insufficiency requiring hemo-or peritoneal dialysis.",
                    "criterion": "renal failure / insufficiency",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": [
                                "hemodialysis",
                                "peritoneal dialysis"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Known severe atheromatosis.",
                    "criterion": "atheromatosis",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        }
                    ]
                },
                {
                    "exact_snippets": "Known uncontrolled blood hypertension (> 160/100 mm/Hg).",
                    "criterion": "blood hypertension",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": "uncontrolled"
                        },
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">",
                                "value": 160,
                                "unit": "mm/Hg"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Allergic to adriamycin chemotherapy drugs，contrast agent or lipiodol;",
            "criterions": [
                {
                    "exact_snippets": "Allergic to adriamycin chemotherapy drugs",
                    "criterion": "allergy to adriamycin chemotherapy drugs",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Allergic to ... contrast agent",
                    "criterion": "allergy to contrast agent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Allergic to ... lipiodol",
                    "criterion": "allergy to lipiodol",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Any agents which could affect the absorption or pharmacokinetics of the study drugs",
            "criterions": [
                {
                    "exact_snippets": "agents which could affect the absorption or pharmacokinetics of the study drugs",
                    "criterion": "agents affecting absorption or pharmacokinetics",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Subjects unable to suffer the discomfort of the artery infusion procedure",
            "criterions": [
                {
                    "exact_snippets": "unable to suffer the discomfort of the artery infusion procedure",
                    "criterion": "tolerance to artery infusion procedure",
                    "requirements": [
                        {
                            "requirement_type": "tolerance",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}