{
    "info": {
        "nct_id": "NCT03927248",
        "official_title": "Pilot Study of Nivolumab and Procaspase Activating Compound-1 (PAC-1) for",
        "inclusion_criteria": "1. Age ≥18 years.\n2. Histologically or cytologically confirmed renal cell carcinoma.\n3. Stage IV disease progressing on prior immune checkpoint inhibitor therapy\n4. Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Appendix 1).\n5. Patients must have anticipated life expectancy greater than 3 months.\n6. Patients must have measurable disease as defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20mm with conventional techniques or as ≥10mm with spiral CT scan by RECIST version 1.1 criteria. Baseline measurements and evaluation of all sites of disease must be obtained within 4 weeks prior to registration.\n7. Palliative radiation must have been completed 2 weeks prior to the initiation of study therapy.\n8. Patient with known brain metastases must have been treated at least 2 weeks prior to enrollment, be asymptomatic from brain metastases, stable on brain imaging, and not be receiving a supra-physiologic dose of steroids (>or = 10 mg prednisone daily or equivalent).\n9. Women must not be pregnant and breast-feeding.\n\n   * All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy.\n   * Women of childbearing potential (WOCBP) must be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 6 months after the last dose of study medication. Patients of childbearing potential are those who have not been surgically sterilized or have not been free of menses > 1 year.\n10. Male patients who are sexually active with WOCBP must agree to use an adequate method of contraception or abstain from sexual intercourse for at least one week prior to starting with the first dose of study therapy through 7 months after the last dose of study therapy.\n11. Required Initial Laboratory Values (tested within 2 weeks prior to registration):\n\n    * Leukocytes ≥2000/ μl\n    * Hemoglobin >9.0 g/dL\n    * Platelets ≥100,000/ μl\n    * ANC ≥1,500/ μl\n    * Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below):\n\n      * Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL\n      * Male CrCl = (140 - age in years) x weight in kg x 1.00\n    * Total Bilirubin <1.5 mg/dl (except for subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dl)\n    * SGOT (AST) <2.5 x ULN\n    * ALP <2.5 x ULN in absence of liver metastases (<5 x ULN if liver metastases present\n    * PTT <1.5 x ULN\n12. The participant is capable of understanding and complying with the protocol and has signed informed consent document.\n\nExclusion Criteria\n\n1. Active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.\n2. Condition requiring systemic treatment with either corticosteroids (> or=10mg/day prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence or active autoimmune disease.\n3. Active hepatitis B or hepatitis C infection.\n4. History of human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).\n5. New York Heart Association class III or IV congestive heart failure.\n6. Corrected QT interval calculated by Fridericia formula (QTcF) > 500 ms within 14 days registration.\n7. Cardiovascular disorders including unstable angina pectoris, clinically-significant cardiac arrhythmias, myocardial infarction or stroke (including transient ischemic attack [TIA], or other ischemic event) within 6 months prior to registration.\n8. Active infection requiring intravenous systemic treatment.\n9. History of organ transplant.\n10. Inability to swallow intact tablets.\nHealthy volunteers allowed\nMust have minimum age of 18 Years\nMust have maximum age of 85 Years",
        "exclusion_criteria": "",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Age ≥18 years.",
            "criterions": [
                {
                    "exact_snippets": "Age ≥18 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Histologically or cytologically confirmed renal cell carcinoma.",
            "criterions": [
                {
                    "exact_snippets": "Histologically or cytologically confirmed renal cell carcinoma",
                    "criterion": "renal cell carcinoma",
                    "requirements": [
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": [
                                "histologically",
                                "cytologically"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Stage IV disease progressing on prior immune checkpoint inhibitor therapy",
            "criterions": [
                {
                    "exact_snippets": "Stage IV disease",
                    "criterion": "disease stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "IV"
                        }
                    ]
                },
                {
                    "exact_snippets": "progressing on prior immune checkpoint inhibitor therapy",
                    "criterion": "response to prior therapy",
                    "requirements": [
                        {
                            "requirement_type": "progression",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "therapy type",
                            "expected_value": "immune checkpoint inhibitor"
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Appendix 1).",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) performance status 0-2",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Patients must have anticipated life expectancy greater than 3 months.",
            "criterions": [
                {
                    "exact_snippets": "anticipated life expectancy greater than 3 months",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Patients must have measurable disease as defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20mm with conventional techniques or as ≥10mm with spiral CT scan by RECIST version 1.1 criteria. Baseline measurements and evaluation of all sites of disease must be obtained within 4 weeks prior to registration.",
            "criterions": [
                {
                    "exact_snippets": "measurable disease as defined as at least one lesion that can be accurately measured in at least one dimension",
                    "criterion": "measurable disease",
                    "requirements": [
                        {
                            "requirement_type": "definition",
                            "expected_value": "at least one lesion that can be accurately measured in at least one dimension"
                        }
                    ]
                },
                {
                    "exact_snippets": "longest diameter to be recorded ... ≥ 20mm with conventional techniques",
                    "criterion": "lesion size with conventional techniques",
                    "requirements": [
                        {
                            "requirement_type": "size",
                            "expected_value": {
                                "operator": ">=",
                                "value": 20,
                                "unit": "mm"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "longest diameter to be recorded ... ≥10mm with spiral CT scan",
                    "criterion": "lesion size with spiral CT scan",
                    "requirements": [
                        {
                            "requirement_type": "size",
                            "expected_value": {
                                "operator": ">=",
                                "value": 10,
                                "unit": "mm"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Baseline measurements and evaluation of all sites of disease must be obtained within 4 weeks prior to registration",
                    "criterion": "baseline measurements and evaluation timing",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "within 4 weeks prior to registration"
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Palliative radiation must have been completed 2 weeks prior to the initiation of study therapy.",
            "criterions": [
                {
                    "exact_snippets": "Palliative radiation must have been completed 2 weeks prior to the initiation of study therapy.",
                    "criterion": "palliative radiation",
                    "requirements": [
                        {
                            "requirement_type": "completion time",
                            "expected_value": {
                                "operator": "<=",
                                "value": -2,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Patient with known brain metastases must have been treated at least 2 weeks prior to enrollment, be asymptomatic from brain metastases, stable on brain imaging, and not be receiving a supra-physiologic dose of steroids (>or = 10 mg prednisone daily or equivalent).",
            "criterions": [
                {
                    "exact_snippets": "known brain metastases",
                    "criterion": "brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "treated at least 2 weeks prior to enrollment",
                    "criterion": "treatment for brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "time since treatment",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "asymptomatic from brain metastases",
                    "criterion": "symptoms from brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "stable on brain imaging",
                    "criterion": "brain imaging stability",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": "stable"
                        }
                    ]
                },
                {
                    "exact_snippets": "not be receiving a supra-physiologic dose of steroids (>or = 10 mg prednisone daily or equivalent)",
                    "criterion": "steroid dose",
                    "requirements": [
                        {
                            "requirement_type": "dose",
                            "expected_value": {
                                "operator": "<",
                                "value": 10,
                                "unit": "mg prednisone daily or equivalent"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Women must not be pregnant and breast-feeding.",
            "criterions": [
                {
                    "exact_snippets": "Women must not be pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Women must not be ... breast-feeding",
                    "criterion": "breast-feeding",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy.",
            "criterions": [
                {
                    "exact_snippets": "females of childbearing potential",
                    "criterion": "females of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "blood test or urine study ... to rule out pregnancy",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "absence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "within 2 weeks prior to registration",
                    "criterion": "timing of test",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Women of childbearing potential (WOCBP) must be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 6 months after the last dose of study medication. Patients of childbearing potential are those who have not been surgically sterilized or have not been free of menses > 1 year.",
            "criterions": [
                {
                    "exact_snippets": "Women of childbearing potential (WOCBP)",
                    "criterion": "gender and reproductive status",
                    "requirements": [
                        {
                            "requirement_type": "gender",
                            "expected_value": "female"
                        },
                        {
                            "requirement_type": "reproductive status",
                            "expected_value": "childbearing potential"
                        }
                    ]
                },
                {
                    "exact_snippets": "must be willing to use 2 methods of birth control",
                    "criterion": "birth control methods",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "methods"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "be surgically sterile",
                    "criterion": "surgical sterilization",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "abstain from heterosexual activity",
                    "criterion": "sexual activity",
                    "requirements": [
                        {
                            "requirement_type": "abstinence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "for the course of the study through 6 months after the last dose of study medication",
                    "criterion": "duration of birth control or abstinence",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "course of the study through 6 months after the last dose"
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients of childbearing potential are those who have not been surgically sterilized",
                    "criterion": "surgical sterilization",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "have not been free of menses > 1 year",
                    "criterion": "menstrual status",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 1,
                                "unit": "year"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Male patients who are sexually active with WOCBP must agree to use an adequate method of contraception or abstain from sexual intercourse for at least one week prior to starting with the first dose of study therapy through 7 months after the last dose of study therapy.",
            "criterions": [
                {
                    "exact_snippets": "Male patients",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "expected_value",
                            "expected_value": "male"
                        }
                    ]
                },
                {
                    "exact_snippets": "sexually active",
                    "criterion": "sexual activity",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "agree to use an adequate method of contraception or abstain from sexual intercourse",
                    "criterion": "contraception or abstinence agreement",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "for at least one week prior to starting with the first dose of study therapy through 7 months after the last dose of study therapy",
                    "criterion": "contraception or abstinence duration",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "at least one week prior to starting with the first dose of study therapy through 7 months after the last dose of study therapy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Required Initial Laboratory Values (tested within 2 weeks prior to registration):",
            "criterions": [
                {
                    "exact_snippets": "Initial Laboratory Values (tested within 2 weeks prior to registration)",
                    "criterion": "initial laboratory values",
                    "requirements": [
                        {
                            "requirement_type": "timeframe",
                            "expected_value": "within 2 weeks prior to registration"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Leukocytes ≥2000/ μl",
            "criterions": [
                {
                    "exact_snippets": "Leukocytes ≥2000/ μl",
                    "criterion": "leukocytes",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2000,
                                "unit": "μl"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Hemoglobin >9.0 g/dL",
            "criterions": [
                {
                    "exact_snippets": "Hemoglobin >9.0 g/dL",
                    "criterion": "hemoglobin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">",
                                "value": 9.0,
                                "unit": "g/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Platelets ≥100,000/ μl",
            "criterions": [
                {
                    "exact_snippets": "Platelets ≥100,000/ μl",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100000,
                                "unit": "/ μl"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* ANC ≥1,500/ μl",
            "criterions": [
                {
                    "exact_snippets": "ANC ≥1,500/ μl",
                    "criterion": "ANC",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1500,
                                "unit": "μl"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below):",
            "criterions": [
                {
                    "exact_snippets": "Serum creatinine ≤ 1.5 x ULN",
                    "criterion": "serum creatinine",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "creatinine clearance (CrCl) ≥ 40 mL/min",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 40,
                                "unit": "mL/min"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL",
            "criterions": [
                {
                    "exact_snippets": "Female",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": "female"
                        }
                    ]
                },
                {
                    "exact_snippets": "CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL",
                    "criterion": "creatinine clearance (CrCl)",
                    "requirements": [
                        {
                            "requirement_type": "calculation",
                            "expected_value": "(140 - age in years) x weight in kg x 0.85 / (72 x serum creatinine in mg/dL)"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Male CrCl = (140 - age in years) x weight in kg x 1.00",
            "criterions": [
                {
                    "exact_snippets": "Male",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": "male"
                        }
                    ]
                },
                {
                    "exact_snippets": "CrCl = (140 - age in years) x weight in kg x 1.00",
                    "criterion": "creatinine clearance (CrCl)",
                    "requirements": [
                        {
                            "requirement_type": "calculation",
                            "expected_value": "(140 - age in years) x weight in kg x 1.00"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Total Bilirubin <1.5 mg/dl (except for subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dl)",
            "criterions": [
                {
                    "exact_snippets": "Total Bilirubin <1.5 mg/dl",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 1.5,
                                "unit": "mg/dl"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Gilbert Syndrome ... total bilirubin < 3.0 mg/dl",
                    "criterion": "total bilirubin in subjects with Gilbert Syndrome",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 3.0,
                                "unit": "mg/dl"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* SGOT (AST) <2.5 x ULN",
            "criterions": [
                {
                    "exact_snippets": "SGOT (AST) <2.5 x ULN",
                    "criterion": "SGOT (AST)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 2.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* PTT <1.5 x ULN",
            "criterions": [
                {
                    "exact_snippets": "PTT <1.5 x ULN",
                    "criterion": "PTT",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. The participant is capable of understanding and complying with the protocol and has signed informed consent document.",
            "criterions": [
                {
                    "exact_snippets": "The participant is capable of understanding",
                    "criterion": "understanding capability",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "complying with the protocol",
                    "criterion": "protocol compliance capability",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "has signed informed consent document",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "signed",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.",
            "criterions": [
                {
                    "exact_snippets": "Active, known or suspected autoimmune disease.",
                    "criterion": "autoimmune disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Subjects are permitted to enroll if they have vitiligo",
                    "criterion": "vitiligo",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "type I diabetes mellitus",
                    "criterion": "type I diabetes mellitus",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "residual hypothyroidism due to autoimmune condition only requiring hormone replacement",
                    "criterion": "residual hypothyroidism due to autoimmune condition",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": "hormone replacement"
                        }
                    ]
                },
                {
                    "exact_snippets": "psoriasis not requiring systemic treatment",
                    "criterion": "psoriasis",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": "not requiring systemic treatment"
                        }
                    ]
                },
                {
                    "exact_snippets": "conditions not expected to recur in the absence of an external trigger",
                    "criterion": "conditions not expected to recur in the absence of an external trigger",
                    "requirements": [
                        {
                            "requirement_type": "recurrence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Condition requiring systemic treatment with either corticosteroids (> or=10mg/day prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence or active autoimmune disease.",
            "criterions": [
                {
                    "exact_snippets": "Condition requiring systemic treatment with either corticosteroids (> or=10mg/day prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration.",
                    "criterion": "systemic treatment with corticosteroids or other immunosuppressive medications",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "within 14 days of study drug administration"
                        },
                        {
                            "requirement_type": "dosage",
                            "expected_value": {
                                "operator": ">=",
                                "value": 10,
                                "unit": "mg/day prednisone equivalents"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence or active autoimmune disease.",
                    "criterion": "inhaled or topical steroids and adrenal replacement doses",
                    "requirements": [
                        {
                            "requirement_type": "dosage",
                            "expected_value": {
                                "operator": ">",
                                "value": 10,
                                "unit": "mg daily prednisone equivalents"
                            }
                        },
                        {
                            "requirement_type": "condition",
                            "expected_value": "absence of active autoimmune disease"
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Active hepatitis B or hepatitis C infection.",
            "criterions": [
                {
                    "exact_snippets": "Active hepatitis B",
                    "criterion": "hepatitis B infection",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        }
                    ]
                },
                {
                    "exact_snippets": "Active ... hepatitis C infection",
                    "criterion": "hepatitis C infection",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. History of human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).",
            "criterions": [
                {
                    "exact_snippets": "History of human immunodeficiency virus (HIV)",
                    "criterion": "human immunodeficiency virus (HIV)",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "known acquired immunodeficiency syndrome (AIDS)",
                    "criterion": "acquired immunodeficiency syndrome (AIDS)",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. New York Heart Association class III or IV congestive heart failure.",
            "criterions": [
                {
                    "exact_snippets": "New York Heart Association class III or IV",
                    "criterion": "New York Heart Association class",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "III",
                                "IV"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "congestive heart failure",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Corrected QT interval calculated by Fridericia formula (QTcF) > 500 ms within 14 days registration.",
            "criterions": [
                {
                    "exact_snippets": "Corrected QT interval calculated by Fridericia formula (QTcF) > 500 ms",
                    "criterion": "Corrected QT interval (QTcF)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">",
                                "value": 500,
                                "unit": "ms"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "within 14 days registration",
                    "criterion": "timeframe for QTcF measurement",
                    "requirements": [
                        {
                            "requirement_type": "timeframe",
                            "expected_value": "within 14 days of registration"
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Cardiovascular disorders including unstable angina pectoris, clinically-significant cardiac arrhythmias, myocardial infarction or stroke (including transient ischemic attack [TIA], or other ischemic event) within 6 months prior to registration.",
            "criterions": [
                {
                    "exact_snippets": "Cardiovascular disorders including unstable angina pectoris",
                    "criterion": "unstable angina pectoris",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "clinically-significant cardiac arrhythmias",
                    "criterion": "clinically-significant cardiac arrhythmias",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "myocardial infarction",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "stroke (including transient ischemic attack [TIA], or other ischemic event)",
                    "criterion": "stroke or other ischemic event",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "within 6 months prior to registration",
                    "criterion": "time since cardiovascular event",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Active infection requiring intravenous systemic treatment.",
            "criterions": [
                {
                    "exact_snippets": "Active infection requiring intravenous systemic treatment.",
                    "criterion": "active infection",
                    "requirements": [
                        {
                            "requirement_type": "treatment type",
                            "expected_value": "intravenous systemic"
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. History of organ transplant.",
            "criterions": [
                {
                    "exact_snippets": "History of organ transplant",
                    "criterion": "organ transplant",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Inability to swallow intact tablets.",
            "criterions": [
                {
                    "exact_snippets": "Inability to swallow intact tablets",
                    "criterion": "ability to swallow intact tablets",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "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 85 Years",
            "criterions": [
                {
                    "exact_snippets": "maximum age of 85 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "maximum",
                            "expected_value": {
                                "operator": "<=",
                                "value": 85,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [],
    "miscellaneous_lines": [],
    "failed_inclusion": [
        {
            "line": "* ALP <2.5 x ULN in absence of liver metastases (<5 x ULN if liver metastases present",
            "criterions": [
                {
                    "exact_snippets": "ALP <2.5 x ULN in absence of liver metastases",
                    "criterion": "ALP level",
                    "requirements": [
                        {
                            "requirement_type": "comparison",
                            "expected_value": {
                                "operator": "<",
                                "value": 2.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "ALP <5 x ULN if liver metastases present",
                    "criterion": "ALP level with liver metastases",
                    "requirements": [
                        {
                            "requirement_type": "comparison",
                            "expected_value": {
                                "operator": "<",
                                "value": 5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Exclusion Criteria",
            "criterions": []
        }
    ],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}