{
    "info": {
        "nct_id": "NCT03573960",
        "official_title": "Prospective Single Arm Post Marketing Phase IV Study to Assess the Safety and Efficacy of Lenvatinib in Subjects With Locally Recurrent or Metastatic, Progressive, Radioiodine Refractory Differentiated Thyroid Cancer",
        "inclusion_criteria": "1. Males and females who are diagnosed with locally Recurrent or Metastatic, Progressive, Radioiodine Refractory DTC, Lenvatinib naive and able to provide written informed consent.\n2. Histologically or cytologically confirmed diagnosis of one of the following DTC subtypes: Papillary thyroid cancer (PTC) (including the follicular variants and other variants), Follicular thyroid cancer (FTC) (including Hurthle cell, Clear cell and Insular subtypes).\n3. Measurable disease meeting the following criteria: i) At least 1 lesion >= 1.0 centimeter (cm) in the longest diameter for a non-lymph node or >= 1.5 cm in the short-axis diameter for a lymph node which is serially measurable according to RECIST 1.1 using computerized tomography/magnetic resonance imaging (CT/MRI). ii) Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies such as radiofrequency (RF) ablation must have shown evidence of PD based on RECIST 1.1 to be deemed a target lesion.\n4. Evidence of disease progression within 12 months of screening scan.\n5. Require thyroxine suppression therapy and thyroid stimulating hormone (TSH) should not be elevated (TSH should be less than [<] 4.0 milli-international units per liter [mIU/L]).\n6. Participant must be radioiodine-refractory or resistant within 12 months of radioiodine therapy and have one of the following:\n\n   * One or more measurable lesions that do not demonstrate iodine uptake on any radioiodine scan.\n   * One or more measurable lesions that have substantially increased in size within 12 months of radioiodine therapy, despite demonstration of radioiodine activity at the time of that treatment by pre- or post-treatment scanning.\n   * Cumulative activity of radioiodine of greater than (>) 600 milliecurie (mCi) or 22 gigabecquerels (GBq), with the last dose administered at least 6 months prior to study entry.\n7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.\n8. Based on following laboratory assessment:\n\n   * Creatinine clearance >= 30 milliliter per minute (mL/min) according to the Cockcroft and Gault formula.\n   * Adequate blood coagulation function as evidenced by an International Normalized Ratio (INR) less than or equal to (<=) 1.5.\n   * Adequate bone marrow function:\n\n     i. Absolute neutrophil count (ANC) >=1.5*10^9/liter (L) ii. Hemoglobin >= 9.0 gram per deciliter (g/dL) (can be corrected by growth factor or transfusion) iii. Platelet count >=100 * 10^9/L\n   * Adequate liver function:\n\n     i. Bilirubin <= 1.5*upper limit of normal (ULN) except for unconjugated hyperbilirubinemia or Gilbert's syndrome.\n\n   ii. Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) <= 3*ULN (<= 5*ULN if participant has liver metastases). If ALP is > 3*ULN (in the absence of liver metastases) or > 5*ULN (in the presence of liver metastases) and participants are also known to have bone metastases, the liver-specific ALP must be separated from the total and used to assess the liver function instead of the total ALP.\n9. Urine dipstick proteinuria should be < 2+. If > or equal 2 gram (g) proteinuria is detected with dipstick, a 24-hour period urine test will be performed and the result should be < or equal to 1 g/24 hours to permit the inclusion of the patient in the clinical trial.\n10. Females of childbearing potential must not have had unprotected sexual intercourse within 30 days before program entry and must agree to use a highly effective method of contraception (example, total abstinence, an intrauterine device, a double-barrier method (such as condom plus diaphragm with spermicide), a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire program.\n\n    * If currently abstinent, participants must agree to use a double-barrier method as described above if they become sexually active during the study period or for 30 days after study drug discontinuation.\n    * Females who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks before dosing and must continue to use the same contraceptive during the study and for 30 days after study drug discontinuation.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "1. Anaplastic or medullary carcinoma of the thyroid.\n2. Two or more prior vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR)-targeted therapies or any ongoing treatment for iodine-131 (131I) refractory DTC other than TSH-suppressive thyroid hormone therapy.\n3. Blood pressure (BP) >= 140 millimeter of mercury (mmHg) Systolic and >= 90 mmHg Diastolic at screening with or without antihypertensive medications.\n4. Woman who are lactating or pregnant at screening or baseline.\n5. Participants who received any anticancer treatment within 21 days or any investigational agent within 30 days prior to the first dose of study drug. (This does not apply to the use of TSH-suppressive thyroid hormone therapy).\n6. Gastrointestinal malabsorption or any other condition that in the opinion of the investigator affected the absorption of Lenvatinib.\n7. Participant has history of congestive heart failure with New York Heart Association (NYHA) Classification > II, unstable angina, myocardial infarction, serious cardiac arrhythmia, or stroke within the past 6 months.\n8. Electrocardiogram (ECG) with QT interval (QTc) interval >= 450 millisecond (msec). (According to Bazett's formula).\n9. Bleeding or thrombotic disorders or use of anticoagulants, such as warfarin, or similar agents requiring therapeutic international normalized ration (INR) monitoring. (Treatment with low molecular weight heparin [LMWH] will be allowed).\n10. Existing anti-cancer therapy-related toxicities of CTCAE version 4.03 grade >= 2, except alopecia and infertility.\n11. Any history of or concomitant medical condition that, in the opinion of the investigator, would compromise participant's ability to safely complete the protocol.\n12. Active infection (any infection requiring treatment).\n13. Active malignancy (except for differentiated thyroid carcinoma, or definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 24 months.\n14. Epistaxis or active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.\n15. Known intolerance to Lenvatinib (or any of the excipients).\n16. Participants with clinically significant laboratory investigations as per the investigator's judgment.\n17. Participation in any interventional clinical study within the past 90 days of enrollment to treatment.\n18. Male or female of childbearing potential, unwilling to use adequate methods of contraception throughout the study.\n19. Participants whom had major surgery within 3 weeks prior to study entry, or who have not recovered from prior major surgery, or whom have surgery scheduled during the course of the study.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Males and females who are diagnosed with locally Recurrent or Metastatic, Progressive, Radioiodine Refractory DTC, Lenvatinib naive and able to provide written informed consent.",
            "criterions": [
                {
                    "exact_snippets": "Males and females",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "male",
                                "female"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "diagnosed with locally Recurrent or Metastatic, Progressive, Radioiodine Refractory DTC",
                    "criterion": "diagnosis",
                    "requirements": [
                        {
                            "requirement_type": "condition",
                            "expected_value": "locally Recurrent or Metastatic, Progressive, Radioiodine Refractory DTC"
                        }
                    ]
                },
                {
                    "exact_snippets": "Lenvatinib naive",
                    "criterion": "prior treatment with Lenvatinib",
                    "requirements": [
                        {
                            "requirement_type": "naivety",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "able to provide written informed consent",
                    "criterion": "ability to provide written informed consent",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Histologically or cytologically confirmed diagnosis of one of the following DTC subtypes: Papillary thyroid cancer (PTC) (including the follicular variants and other variants), Follicular thyroid cancer (FTC) (including Hurthle cell, Clear cell and Insular subtypes).",
            "criterions": [
                {
                    "exact_snippets": "Histologically or cytologically confirmed diagnosis of one of the following DTC subtypes: Papillary thyroid cancer (PTC) (including the follicular variants and other variants)",
                    "criterion": "Papillary thyroid cancer (PTC)",
                    "requirements": [
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": [
                                "histologically",
                                "cytologically"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Histologically or cytologically confirmed diagnosis of one of the following DTC subtypes: ... Follicular thyroid cancer (FTC) (including Hurthle cell, Clear cell and Insular subtypes)",
                    "criterion": "Follicular thyroid cancer (FTC)",
                    "requirements": [
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": [
                                "histologically",
                                "cytologically"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Measurable disease meeting the following criteria: i) At least 1 lesion >= 1.0 centimeter (cm) in the longest diameter for a non-lymph node or >= 1.5 cm in the short-axis diameter for a lymph node which is serially measurable according to RECIST 1.1 using computerized tomography/magnetic resonance imaging (CT/MRI). ii) Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies such as radiofrequency (RF) ablation must have shown evidence of PD based on RECIST 1.1 to be deemed a target lesion.",
            "criterions": [
                {
                    "exact_snippets": "Measurable disease meeting the following criteria: i) At least 1 lesion >= 1.0 centimeter (cm) in the longest diameter for a non-lymph node",
                    "criterion": "non-lymph node lesion size",
                    "requirements": [
                        {
                            "requirement_type": "size",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.0,
                                "unit": "cm"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Measurable disease meeting the following criteria: ... >= 1.5 cm in the short-axis diameter for a lymph node",
                    "criterion": "lymph node lesion size",
                    "requirements": [
                        {
                            "requirement_type": "size",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.5,
                                "unit": "cm"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Measurable disease meeting the following criteria: ... which is serially measurable according to RECIST 1.1 using computerized tomography/magnetic resonance imaging (CT/MRI)",
                    "criterion": "lesion measurability",
                    "requirements": [
                        {
                            "requirement_type": "measurability",
                            "expected_value": "serially measurable according to RECIST 1.1 using CT/MRI"
                        }
                    ]
                },
                {
                    "exact_snippets": "Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies such as radiofrequency (RF) ablation must have shown evidence of PD based on RECIST 1.1 to be deemed a target lesion",
                    "criterion": "lesion post-therapy progression",
                    "requirements": [
                        {
                            "requirement_type": "progression",
                            "expected_value": "evidence of PD based on RECIST 1.1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Evidence of disease progression within 12 months of screening scan.",
            "criterions": [
                {
                    "exact_snippets": "Evidence of disease progression within 12 months of screening scan.",
                    "criterion": "disease progression",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 12 months of screening scan"
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Require thyroxine suppression therapy and thyroid stimulating hormone (TSH) should not be elevated (TSH should be less than [<] 4.0 milli-international units per liter [mIU/L]).",
            "criterions": [
                {
                    "exact_snippets": "Require thyroxine suppression therapy",
                    "criterion": "thyroxine suppression therapy",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "thyroid stimulating hormone (TSH) should not be elevated (TSH should be less than [<] 4.0 milli-international units per liter [mIU/L])",
                    "criterion": "thyroid stimulating hormone (TSH)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 4.0,
                                "unit": "mIU/L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Participant must be radioiodine-refractory or resistant within 12 months of radioiodine therapy and have one of the following:",
            "criterions": [
                {
                    "exact_snippets": "Participant must be radioiodine-refractory or resistant",
                    "criterion": "radioiodine-refractory or resistant",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "within 12 months of radioiodine therapy",
                    "criterion": "time since radioiodine therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since therapy",
                            "expected_value": {
                                "operator": "<=",
                                "value": 12,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* One or more measurable lesions that do not demonstrate iodine uptake on any radioiodine scan.",
            "criterions": [
                {
                    "exact_snippets": "One or more measurable lesions",
                    "criterion": "measurable lesions",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "do not demonstrate iodine uptake on any radioiodine scan",
                    "criterion": "iodine uptake on radioiodine scan",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* One or more measurable lesions that have substantially increased in size within 12 months of radioiodine therapy, despite demonstration of radioiodine activity at the time of that treatment by pre- or post-treatment scanning.",
            "criterions": [
                {
                    "exact_snippets": "One or more measurable lesions",
                    "criterion": "measurable lesions",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "substantially increased in size within 12 months of radioiodine therapy",
                    "criterion": "lesion size increase",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 12 months of radioiodine therapy"
                        },
                        {
                            "requirement_type": "size increase",
                            "expected_value": "substantially increased"
                        }
                    ]
                },
                {
                    "exact_snippets": "despite demonstration of radioiodine activity at the time of that treatment",
                    "criterion": "radioiodine activity",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Cumulative activity of radioiodine of greater than (>) 600 milliecurie (mCi) or 22 gigabecquerels (GBq), with the last dose administered at least 6 months prior to study entry.",
            "criterions": [
                {
                    "exact_snippets": "Cumulative activity of radioiodine of greater than (>) 600 milliecurie (mCi) or 22 gigabecquerels (GBq)",
                    "criterion": "cumulative activity of radioiodine",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">",
                                        "value": 600,
                                        "unit": "mCi"
                                    },
                                    {
                                        "operator": ">",
                                        "value": 22,
                                        "unit": "GBq"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "last dose administered at least 6 months prior to study entry",
                    "criterion": "time since last radioiodine dose",
                    "requirements": [
                        {
                            "requirement_type": "time elapsed",
                            "expected_value": {
                                "operator": ">=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Creatinine clearance >= 30 milliliter per minute (mL/min) according to the Cockcroft and Gault formula.",
            "criterions": [
                {
                    "exact_snippets": "Creatinine clearance >= 30 milliliter per minute (mL/min)",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 30,
                                "unit": "milliliter per minute (mL/min)"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate blood coagulation function as evidenced by an International Normalized Ratio (INR) less than or equal to (<=) 1.5.",
            "criterions": [
                {
                    "exact_snippets": "Adequate blood coagulation function ... International Normalized Ratio (INR) less than or equal to (<=) 1.5.",
                    "criterion": "blood coagulation function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "INR",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "N/A"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate bone marrow function:",
            "criterions": [
                {
                    "exact_snippets": "Adequate bone marrow function",
                    "criterion": "bone marrow function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "i. Absolute neutrophil count (ANC) >=1.5*10^9/liter (L) ii. Hemoglobin >= 9.0 gram per deciliter (g/dL) (can be corrected by growth factor or transfusion) iii. Platelet count >=100 * 10^9/L",
            "criterions": [
                {
                    "exact_snippets": "Absolute neutrophil count (ANC) >=1.5*10^9/liter (L)",
                    "criterion": "absolute neutrophil count (ANC)",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.5,
                                "unit": "10^9/liter"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Hemoglobin >= 9.0 gram per deciliter (g/dL)",
                    "criterion": "hemoglobin",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 9.0,
                                "unit": "gram per deciliter (g/dL)"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Platelet count >=100 * 10^9/L",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100,
                                "unit": "10^9/L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate liver function:",
            "criterions": [
                {
                    "exact_snippets": "Adequate liver function",
                    "criterion": "liver function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "i. Bilirubin <= 1.5*upper limit of normal (ULN) except for unconjugated hyperbilirubinemia or Gilbert's syndrome.",
            "criterions": [
                {
                    "exact_snippets": "Bilirubin <= 1.5*upper limit of normal (ULN)",
                    "criterion": "bilirubin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "*ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "except for unconjugated hyperbilirubinemia",
                    "criterion": "unconjugated hyperbilirubinemia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "except for ... Gilbert's syndrome",
                    "criterion": "Gilbert's syndrome",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "ii. Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) <= 3*ULN (<= 5*ULN if participant has liver metastases). If ALP is > 3*ULN (in the absence of liver metastases) or > 5*ULN (in the presence of liver metastases) and participants are also known to have bone metastases, the liver-specific ALP must be separated from the total and used to assess the liver function instead of the total ALP.",
            "criterions": [
                {
                    "exact_snippets": "Alkaline phosphatase (ALP) ... <= 3*ULN (<= 5*ULN if participant has liver metastases)",
                    "criterion": "alkaline phosphatase (ALP)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 3,
                                        "unit": "ULN"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "alanine aminotransferase (ALT) ... <= 3*ULN",
                    "criterion": "alanine aminotransferase (ALT)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 3,
                                        "unit": "ULN"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "aspartate aminotransferase (AST) ... <= 3*ULN",
                    "criterion": "aspartate aminotransferase (AST)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 3,
                                        "unit": "ULN"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "ALP is > 3*ULN (in the absence of liver metastases)",
                    "criterion": "alkaline phosphatase (ALP)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">",
                                        "value": 3,
                                        "unit": "ULN"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "ALP is ... > 5*ULN (in the presence of liver metastases)",
                    "criterion": "alkaline phosphatase (ALP)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">",
                                        "value": 5,
                                        "unit": "ULN"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "participants are also known to have bone metastases",
                    "criterion": "bone metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "liver-specific ALP must be separated from the total and used to assess the liver function",
                    "criterion": "liver-specific alkaline phosphatase (ALP)",
                    "requirements": [
                        {
                            "requirement_type": "usage",
                            "expected_value": "separated from total ALP for liver function assessment"
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Urine dipstick proteinuria should be < 2+. If > or equal 2 gram (g) proteinuria is detected with dipstick, a 24-hour period urine test will be performed and the result should be < or equal to 1 g/24 hours to permit the inclusion of the patient in the clinical trial.",
            "criterions": [
                {
                    "exact_snippets": "Urine dipstick proteinuria should be < 2+",
                    "criterion": "urine dipstick proteinuria",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<",
                                "value": 2,
                                "unit": "+"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "If > or equal 2 gram (g) proteinuria is detected with dipstick",
                    "criterion": "dipstick proteinuria",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "g"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "24-hour period urine test ... result should be < or equal to 1 g/24 hours",
                    "criterion": "24-hour urine proteinuria",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "g/24 hours"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Females of childbearing potential must not have had unprotected sexual intercourse within 30 days before program entry and must agree to use a highly effective method of contraception (example, total abstinence, an intrauterine device, a double-barrier method (such as condom plus diaphragm with spermicide), a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire program.",
            "criterions": [
                {
                    "exact_snippets": "Females of childbearing potential",
                    "criterion": "gender and reproductive status",
                    "requirements": [
                        {
                            "requirement_type": "gender",
                            "expected_value": "female"
                        },
                        {
                            "requirement_type": "reproductive status",
                            "expected_value": "childbearing potential"
                        }
                    ]
                },
                {
                    "exact_snippets": "must not have had unprotected sexual intercourse within 30 days before program entry",
                    "criterion": "unprotected sexual intercourse",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 30,
                                "unit": "days"
                            }
                        },
                        {
                            "requirement_type": "occurrence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "must agree to use a highly effective method of contraception",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "(example, total abstinence, an intrauterine device, a double-barrier method (such as condom plus diaphragm with spermicide), a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia)",
                    "criterion": "contraception methods",
                    "requirements": [
                        {
                            "requirement_type": "methods",
                            "expected_value": [
                                "total abstinence",
                                "intrauterine device",
                                "double-barrier method",
                                "contraceptive implant",
                                "oral contraceptive",
                                "vasectomized partner with confirmed azoospermia"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* If currently abstinent, participants must agree to use a double-barrier method as described above if they become sexually active during the study period or for 30 days after study drug discontinuation.",
            "criterions": [
                {
                    "exact_snippets": "currently abstinent",
                    "criterion": "abstinence",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "abstinent"
                        }
                    ]
                },
                {
                    "exact_snippets": "agree to use a double-barrier method ... if they become sexually active",
                    "criterion": "contraceptive method",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": "double-barrier"
                        }
                    ]
                },
                {
                    "exact_snippets": "during the study period or for 30 days after study drug discontinuation",
                    "criterion": "contraceptive method duration",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "during the study period or for 30 days after study drug discontinuation"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Females who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks before dosing and must continue to use the same contraceptive during the study and for 30 days after study drug discontinuation.",
            "criterions": [
                {
                    "exact_snippets": "Females who are using hormonal contraceptives",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": "female"
                        }
                    ]
                },
                {
                    "exact_snippets": "Females who are using hormonal contraceptives",
                    "criterion": "hormonal contraceptive use",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks before dosing",
                    "criterion": "hormonal contraceptive stability",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "must continue to use the same contraceptive during the study and for 30 days after study drug discontinuation",
                    "criterion": "hormonal contraceptive continuation",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 30,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "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"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "1. Anaplastic or medullary carcinoma of the thyroid.",
            "criterions": [
                {
                    "exact_snippets": "Anaplastic ... carcinoma of the thyroid.",
                    "criterion": "anaplastic carcinoma of the thyroid",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "medullary carcinoma of the thyroid.",
                    "criterion": "medullary carcinoma of the thyroid",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Two or more prior vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR)-targeted therapies or any ongoing treatment for iodine-131 (131I) refractory DTC other than TSH-suppressive thyroid hormone therapy.",
            "criterions": [
                {
                    "exact_snippets": "Two or more prior vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR)-targeted therapies",
                    "criterion": "prior VEGF/VEGFR-targeted therapies",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "any ongoing treatment for iodine-131 (131I) refractory DTC other than TSH-suppressive thyroid hormone therapy",
                    "criterion": "ongoing treatment for iodine-131 refractory DTC",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": [
                                "TSH-suppressive thyroid hormone therapy"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Blood pressure (BP) >= 140 millimeter of mercury (mmHg) Systolic and >= 90 mmHg Diastolic at screening with or without antihypertensive medications.",
            "criterions": [
                {
                    "exact_snippets": "Blood pressure (BP) >= 140 millimeter of mercury (mmHg) Systolic",
                    "criterion": "systolic blood pressure",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 140,
                                "unit": "mmHg"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Blood pressure (BP) ... >= 90 mmHg Diastolic",
                    "criterion": "diastolic blood pressure",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 90,
                                "unit": "mmHg"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Woman who are lactating or pregnant at screening or baseline.",
            "criterions": [
                {
                    "exact_snippets": "Woman who are lactating",
                    "criterion": "lactation status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "lactating"
                        }
                    ]
                },
                {
                    "exact_snippets": "Woman who are ... pregnant",
                    "criterion": "pregnancy status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "pregnant"
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Participants who received any anticancer treatment within 21 days or any investigational agent within 30 days prior to the first dose of study drug. (This does not apply to the use of TSH-suppressive thyroid hormone therapy).",
            "criterions": [
                {
                    "exact_snippets": "Participants who received any anticancer treatment within 21 days",
                    "criterion": "anticancer treatment",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 21,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "any investigational agent within 30 days prior to the first dose of study drug",
                    "criterion": "investigational agent",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 30,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Gastrointestinal malabsorption or any other condition that in the opinion of the investigator affected the absorption of Lenvatinib.",
            "criterions": [
                {
                    "exact_snippets": "Gastrointestinal malabsorption",
                    "criterion": "gastrointestinal malabsorption",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "any other condition ... affected the absorption of Lenvatinib",
                    "criterion": "condition affecting absorption of Lenvatinib",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Participant has history of congestive heart failure with New York Heart Association (NYHA) Classification > II, unstable angina, myocardial infarction, serious cardiac arrhythmia, or stroke within the past 6 months.",
            "criterions": [
                {
                    "exact_snippets": "history of congestive heart failure",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "New York Heart Association (NYHA) Classification > II",
                    "criterion": "NYHA Classification",
                    "requirements": [
                        {
                            "requirement_type": "classification",
                            "expected_value": {
                                "operator": ">",
                                "value": 2,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "unstable angina",
                    "criterion": "unstable angina",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "myocardial infarction",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "occurrence",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "serious cardiac arrhythmia",
                    "criterion": "serious cardiac arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "stroke within the past 6 months",
                    "criterion": "stroke",
                    "requirements": [
                        {
                            "requirement_type": "occurrence",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Electrocardiogram (ECG) with QT interval (QTc) interval >= 450 millisecond (msec). (According to Bazett's formula).",
            "criterions": [
                {
                    "exact_snippets": "Electrocardiogram (ECG) with QT interval (QTc) interval >= 450 millisecond (msec).",
                    "criterion": "QTc interval",
                    "requirements": [
                        {
                            "requirement_type": "length",
                            "expected_value": {
                                "operator": ">=",
                                "value": 450,
                                "unit": "millisecond"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Bleeding or thrombotic disorders or use of anticoagulants, such as warfarin, or similar agents requiring therapeutic international normalized ration (INR) monitoring. (Treatment with low molecular weight heparin [LMWH] will be allowed).",
            "criterions": [
                {
                    "exact_snippets": "Bleeding or thrombotic disorders",
                    "criterion": "bleeding or thrombotic disorders",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "use of anticoagulants, such as warfarin, or similar agents requiring therapeutic international normalized ration (INR) monitoring",
                    "criterion": "use of anticoagulants",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Treatment with low molecular weight heparin [LMWH] will be allowed",
                    "criterion": "treatment with low molecular weight heparin [LMWH]",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Existing anti-cancer therapy-related toxicities of CTCAE version 4.03 grade >= 2, except alopecia and infertility.",
            "criterions": [
                {
                    "exact_snippets": "Existing anti-cancer therapy-related toxicities of CTCAE version 4.03 grade >= 2",
                    "criterion": "anti-cancer therapy-related toxicities",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "CTCAE version 4.03 grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "except alopecia",
                    "criterion": "alopecia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "except ... infertility",
                    "criterion": "infertility",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Any history of or concomitant medical condition that, in the opinion of the investigator, would compromise participant's ability to safely complete the protocol.",
            "criterions": [
                {
                    "exact_snippets": "Any history of or concomitant medical condition",
                    "criterion": "medical condition",
                    "requirements": [
                        {
                            "requirement_type": "impact on protocol completion",
                            "expected_value": "compromise participant's ability to safely complete the protocol"
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. Active infection (any infection requiring treatment).",
            "criterions": [
                {
                    "exact_snippets": "Active infection (any infection requiring treatment)",
                    "criterion": "active infection",
                    "requirements": [
                        {
                            "requirement_type": "treatment requirement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. Active malignancy (except for differentiated thyroid carcinoma, or definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 24 months.",
            "criterions": [
                {
                    "exact_snippets": "Active malignancy (except for differentiated thyroid carcinoma, or definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix)",
                    "criterion": "active malignancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "within the past 24 months",
                    "criterion": "active malignancy",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 24,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "14. Epistaxis or active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.",
            "criterions": [
                {
                    "exact_snippets": "Epistaxis",
                    "criterion": "epistaxis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 3 weeks prior to the first dose of study drug"
                        }
                    ]
                },
                {
                    "exact_snippets": "active hemoptysis (bright red blood of at least 0.5 teaspoon)",
                    "criterion": "active hemoptysis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 0.5,
                                "unit": "teaspoon"
                            }
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 3 weeks prior to the first dose of study drug"
                        }
                    ]
                }
            ]
        },
        {
            "line": "15. Known intolerance to Lenvatinib (or any of the excipients).",
            "criterions": [
                {
                    "exact_snippets": "Known intolerance to Lenvatinib",
                    "criterion": "intolerance to Lenvatinib",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "intolerance to ... any of the excipients",
                    "criterion": "intolerance to excipients",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "16. Participants with clinically significant laboratory investigations as per the investigator's judgment.",
            "criterions": [
                {
                    "exact_snippets": "clinically significant laboratory investigations",
                    "criterion": "laboratory investigations",
                    "requirements": [
                        {
                            "requirement_type": "significance",
                            "expected_value": "clinically significant"
                        },
                        {
                            "requirement_type": "judgment",
                            "expected_value": "investigator's judgment"
                        }
                    ]
                }
            ]
        },
        {
            "line": "17. Participation in any interventional clinical study within the past 90 days of enrollment to treatment.",
            "criterions": [
                {
                    "exact_snippets": "Participation in any interventional clinical study within the past 90 days",
                    "criterion": "participation in interventional clinical study",
                    "requirements": [
                        {
                            "requirement_type": "time since last participation",
                            "expected_value": {
                                "operator": "<=",
                                "value": 90,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "18. Male or female of childbearing potential, unwilling to use adequate methods of contraception throughout the study.",
            "criterions": [
                {
                    "exact_snippets": "Male or female of childbearing potential",
                    "criterion": "childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "unwilling to use adequate methods of contraception throughout the study",
                    "criterion": "use of contraception",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "19. Participants whom had major surgery within 3 weeks prior to study entry, or who have not recovered from prior major surgery, or whom have surgery scheduled during the course of the study.",
            "criterions": [
                {
                    "exact_snippets": "Participants whom had major surgery within 3 weeks prior to study entry",
                    "criterion": "major surgery",
                    "requirements": [
                        {
                            "requirement_type": "time since surgery",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "who have not recovered from prior major surgery",
                    "criterion": "recovery from major surgery",
                    "requirements": [
                        {
                            "requirement_type": "recovery status",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "whom have surgery scheduled during the course of the study",
                    "criterion": "scheduled surgery",
                    "requirements": [
                        {
                            "requirement_type": "scheduled during study",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [
        {
            "line": "8. Based on following laboratory assessment:",
            "criterions": []
        }
    ],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}