{
    "info": {
        "nct_id": "NCT05791448",
        "official_title": "First in Human Dose Escalation Study of AU409 in Patients With Advanced Primary Liver Cancers or Advanced Solid Tumor With Liver Predominant Metastatic Disease",
        "inclusion_criteria": "* Age >= 18 years old\n* Patients must have histopathologically /cytologically confirmed advanced solid tumor, which is refractory to standard therapeutic options, or for which there are no standard therapeutic options. Failure of all approved therapies that have a marginal impact on survival is not required as long as the treating physician considers that treatment on study is appropriate for the subject and documents that the subject elects to defer the approved therapies\n* During the dose-escalation portion, patients must have primary liver malignancy (including hepatocellular carcinoma or cholangiocarcinoma) OR a solid tumor with liver dominant disease; liver dominant disease is defined as the majority of the tumor burden being in the liver per investigator assessment AND no more than two extrahepatic sites of disease (site of disease refers to organ or system). During the dose expansion portion of the study, eligibility may be limited to one or more tumor types depending on findings from the dose-escalation phase; this will be clarified in an amendment\n* Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1\n* Patient must have recovered from any toxic effects of previous chemotherapy, targeted therapy or radiotherapy as judged by the Investigator to =< grade 1 (except for alopecia). Residual sensory neuropathy =< grade 2 is allowed. Residual endocrine adverse events (such as hypothyroidism or hypoadrenalism) that are manageable with replacement therapy are allowed\n* Previous chemotherapy/radiotherapy/targeted/immunotherapy therapy should have been completed at least 4 weeks prior to start of AU409 administration, or five half-lives, whichever is shorter (except for palliative radiation therapy that should be completed >= 14 days prior to study entry)\n* Patients must have an estimated life expectancy of at least 3 months\n* Women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation. A male participant must agree to use highly effective contraception during the intervention period and for 60 days after the last dose of AU409 and refrain from donating sperm during this period. WOCBP are eligible to participate if they are not pregnant, not breastfeeding, and agree to follow the contraceptive guidance during the study intervention period and for at least 90 days after the last dose of AU409\n\n  * Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately\n* A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: Has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)\n* Patients must agree, as part of the informed consent, to undergo liver biopsy (for a subset of patients enrolled at and above dose level 4) and to provide blood for pharmacokinetics analysis\n* Absolute neutrophil count (ANC) >= 1500/mm^3\n* Platelet count >= 100,000/mm^3\n* Hemoglobin >= 8 g/dL (prior transfusion is allowed if completed 2 weeks prior to screening and hemoglobin remains >= 8 g/dL)\n* For patients with HCC with splenic sequestration: ANC >= 1000/mm^3\n* For patients with HCC with splenic sequestration: Platelets >= 70,000\n* Calculated clearance >= 60 mL/min/1.73 m^2. Actual body weight should be used for calculating creatinine clearance (e.g., using the Cockroft-Gault formula). For subjects with a Body Mass Index (BMI) > 30 kg/m^2, lean body weight should be used instead\n* Total bilirubin =< 1.5 X upper limit of normal (ULN) (subjects with known Gilbert's hepatic function disease can have bilirubin of up to 2 X ULN)\n* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 X ULN; or AST/ALT =< 5 X ULN if patient has liver tumors\n* Prothrombin time (PT)/international normalized ratio (INR) =< 1.8 times upper limit of normal (unless patient is on anticoagulation)\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Patients who have had hypersensitivity to pentamidine or any excipients of AU409\n* Treatment with other anticancer therapies (including surgery, radiation therapy, chemotherapy, anti-angiogenic therapy, targeted therapy, or radiofrequency ablation therapy, etc.) or investigational therapy within 28 days prior to study entry (except for palliative radiation therapy that should be completed >= 14 days prior to study entry)\n* Hepatocellular carcinoma patients with a Child Pugh score >= B7\n* Patients with known central nervous system metastases which are untreated or symptomatic; patients with treated brain metastases (completed >= 30 days prior to screening) are allowed provided they are asymptomatic and are off steroids\n* Patient with a history of the following within 6 months prior to cycle 1 day 1: a myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) Class III-IV heart failure, uncontrolled hypertension, clinically significant cardiac dysrhythmia, cerebrovascular accident, transient ischemic attack, or seizure disorder. Atrial fibrillation is allowed if rate is controlled\n* Patients who have corrected QT (QTc) interval to > 470 msec (Fredericia's equation) on 2 out of 3 electrocardiogram (ECG)'s (if first ECG has QTc < 470, no need to repeat, if first ECG has QTc > 470 repeat twice for a total of 3 ECG's)\n* Patients who are on therapeutic anticoagulation with warfarin; however, patients on therapeutic doses of with low molecular weight heparins or Factor Xa inhibitors are eligible\n* Patient with history of gastrointestinal surgery or malabsorptive conditions that may change the absorption of drugs and/or cause rapid transit (such as total gastrectomy, small bowel resection, etc.)\n* Patients who have known active hepatitis B. Patients with chronic hepatitis B who are on anti-viral therapy and have a hepatitis B viral load of =< 500 IU/mL are allowed on the study. Patients with chronic Hepatitis C are allowed\n* Patients who have active infection requiring treatment (except hepatitis B and C as noted above) including known human immunodeficiency virus (HIV) infection\n* Patients who have concurrent conditions resulting in immune compromise, including chronic treatment with corticosteroids or other immunosuppressive agents\n* Patients who have any other condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results\n* Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants\n* Patients who are on medications that are considered to be strong inducers or inhibitors of the cytochrome P450 isoenzymes should have such medications discontinued or replaced. Such medications should be avoided for one week prior to first dose of treatment and during the trial participation. If these medications are absolutely necessary for the patient and cannot be replaced, enrollment may still be considered on a case by case basis if it is in the patient's best interest and after discussion with the principal investigator (PI)",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Age >= 18 years old",
            "criterions": [
                {
                    "exact_snippets": "Age >= 18 years old",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must have histopathologically /cytologically confirmed advanced solid tumor, which is refractory to standard therapeutic options, or for which there are no standard therapeutic options. Failure of all approved therapies that have a marginal impact on survival is not required as long as the treating physician considers that treatment on study is appropriate for the subject and documents that the subject elects to defer the approved therapies",
            "criterions": [
                {
                    "exact_snippets": "histopathologically /cytologically confirmed advanced solid tumor",
                    "criterion": "advanced solid tumor",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": "histopathologically /cytologically"
                        }
                    ]
                },
                {
                    "exact_snippets": "refractory to standard therapeutic options",
                    "criterion": "refractory to standard therapeutic options",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "refractory"
                        }
                    ]
                },
                {
                    "exact_snippets": "no standard therapeutic options",
                    "criterion": "standard therapeutic options",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* During the dose-escalation portion, patients must have primary liver malignancy (including hepatocellular carcinoma or cholangiocarcinoma) OR a solid tumor with liver dominant disease; liver dominant disease is defined as the majority of the tumor burden being in the liver per investigator assessment AND no more than two extrahepatic sites of disease (site of disease refers to organ or system). During the dose expansion portion of the study, eligibility may be limited to one or more tumor types depending on findings from the dose-escalation phase; this will be clarified in an amendment",
            "criterions": [
                {
                    "exact_snippets": "primary liver malignancy (including hepatocellular carcinoma or cholangiocarcinoma)",
                    "criterion": "primary liver malignancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "solid tumor with liver dominant disease",
                    "criterion": "solid tumor with liver dominant disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "liver dominant disease is defined as the majority of the tumor burden being in the liver",
                    "criterion": "liver dominant disease",
                    "requirements": [
                        {
                            "requirement_type": "tumor burden location",
                            "expected_value": "majority in the liver"
                        }
                    ]
                },
                {
                    "exact_snippets": "no more than two extrahepatic sites of disease",
                    "criterion": "extrahepatic sites of disease",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "sites"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": [
                                "0",
                                "1"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patient must have recovered from any toxic effects of previous chemotherapy, targeted therapy or radiotherapy as judged by the Investigator to =< grade 1 (except for alopecia). Residual sensory neuropathy =< grade 2 is allowed. Residual endocrine adverse events (such as hypothyroidism or hypoadrenalism) that are manageable with replacement therapy are allowed",
            "criterions": [
                {
                    "exact_snippets": "recovered from any toxic effects of previous chemotherapy, targeted therapy or radiotherapy ... =< grade 1",
                    "criterion": "recovery from toxic effects of previous therapy",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Residual sensory neuropathy =< grade 2 is allowed",
                    "criterion": "residual sensory neuropathy",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Residual endocrine adverse events (such as hypothyroidism or hypoadrenalism) that are manageable with replacement therapy are allowed",
                    "criterion": "residual endocrine adverse events",
                    "requirements": [
                        {
                            "requirement_type": "manageability",
                            "expected_value": "manageable with replacement therapy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Previous chemotherapy/radiotherapy/targeted/immunotherapy therapy should have been completed at least 4 weeks prior to start of AU409 administration, or five half-lives, whichever is shorter (except for palliative radiation therapy that should be completed >= 14 days prior to study entry)",
            "criterions": [
                {
                    "exact_snippets": "Previous chemotherapy/radiotherapy/targeted/immunotherapy therapy should have been completed at least 4 weeks prior to start of AU409 administration, or five half-lives, whichever is shorter",
                    "criterion": "previous therapy completion",
                    "requirements": [
                        {
                            "requirement_type": "time since completion",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "except for palliative radiation therapy that should be completed >= 14 days prior to study entry",
                    "criterion": "palliative radiation therapy completion",
                    "requirements": [
                        {
                            "requirement_type": "time since completion",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 14,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must have an estimated life expectancy of at least 3 months",
            "criterions": [
                {
                    "exact_snippets": "estimated life expectancy of at least 3 months",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation. A male participant must agree to use highly effective contraception during the intervention period and for 60 days after the last dose of AU409 and refrain from donating sperm during this period. WOCBP are eligible to participate if they are not pregnant, not breastfeeding, and agree to follow the contraceptive guidance during the study intervention period and for at least 90 days after the last dose of AU409",
            "criterions": [
                {
                    "exact_snippets": "Women of child-bearing potential (WOCBP) ... must agree to use adequate contraception",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "men must agree to use adequate contraception",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "A male participant must agree to use highly effective contraception during the intervention period and for 60 days after the last dose of AU409",
                    "criterion": "contraception use duration for men",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "during the intervention period and for 60 days after the last dose of AU409"
                        }
                    ]
                },
                {
                    "exact_snippets": "refrain from donating sperm during this period",
                    "criterion": "sperm donation",
                    "requirements": [
                        {
                            "requirement_type": "refrain",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "WOCBP are eligible to participate if they are not pregnant",
                    "criterion": "pregnancy status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "not pregnant"
                        }
                    ]
                },
                {
                    "exact_snippets": "WOCBP are eligible to participate if they are ... not breastfeeding",
                    "criterion": "breastfeeding status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "not breastfeeding"
                        }
                    ]
                },
                {
                    "exact_snippets": "WOCBP ... agree to follow the contraceptive guidance during the study intervention period and for at least 90 days after the last dose of AU409",
                    "criterion": "contraceptive guidance adherence for WOCBP",
                    "requirements": [
                        {
                            "requirement_type": "adherence",
                            "expected_value": "during the study intervention period and for at least 90 days after the last dose of AU409"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately",
            "criterions": [
                {
                    "exact_snippets": "Should a woman become pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "suspect she is pregnant",
                    "criterion": "suspected pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: Has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)",
            "criterions": [
                {
                    "exact_snippets": "female of child-bearing potential",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "expected_value",
                            "expected_value": "female"
                        }
                    ]
                },
                {
                    "exact_snippets": "Has not undergone a hysterectomy",
                    "criterion": "hysterectomy",
                    "requirements": [
                        {
                            "requirement_type": "underwent",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "bilateral oophorectomy",
                    "criterion": "bilateral oophorectomy",
                    "requirements": [
                        {
                            "requirement_type": "underwent",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "naturally postmenopausal for at least 12 consecutive months",
                    "criterion": "menopausal status",
                    "requirements": [
                        {
                            "requirement_type": "postmenopausal duration",
                            "expected_value": {
                                "operator": "<",
                                "value": 12,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must agree, as part of the informed consent, to undergo liver biopsy (for a subset of patients enrolled at and above dose level 4) and to provide blood for pharmacokinetics analysis",
            "criterions": [
                {
                    "exact_snippets": "Patients must agree, as part of the informed consent, to undergo liver biopsy",
                    "criterion": "liver biopsy",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "provide blood for pharmacokinetics analysis",
                    "criterion": "blood for pharmacokinetics analysis",
                    "requirements": [
                        {
                            "requirement_type": "provision",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Absolute neutrophil count (ANC) >= 1500/mm^3",
            "criterions": [
                {
                    "exact_snippets": "Absolute neutrophil count (ANC) >= 1500/mm^3",
                    "criterion": "absolute neutrophil count (ANC)",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1500,
                                "unit": "mm^3"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Platelet count >= 100,000/mm^3",
            "criterions": [
                {
                    "exact_snippets": "Platelet count >= 100,000/mm^3",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100000,
                                "unit": "mm^3"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Hemoglobin >= 8 g/dL (prior transfusion is allowed if completed 2 weeks prior to screening and hemoglobin remains >= 8 g/dL)",
            "criterions": [
                {
                    "exact_snippets": "Hemoglobin >= 8 g/dL",
                    "criterion": "hemoglobin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 8,
                                "unit": "g/dL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "prior transfusion is allowed if completed 2 weeks prior to screening",
                    "criterion": "prior transfusion",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "completed 2 weeks prior to screening"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* For patients with HCC with splenic sequestration: ANC >= 1000/mm^3",
            "criterions": [
                {
                    "exact_snippets": "patients with HCC",
                    "criterion": "HCC",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "splenic sequestration",
                    "criterion": "splenic sequestration",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "ANC >= 1000/mm^3",
                    "criterion": "ANC",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1000,
                                "unit": "mm^3"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* For patients with HCC with splenic sequestration: Platelets >= 70,000",
            "criterions": [
                {
                    "exact_snippets": "HCC",
                    "criterion": "HCC",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "splenic sequestration",
                    "criterion": "splenic sequestration",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Platelets >= 70,000",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 70000,
                                "unit": ""
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Calculated clearance >= 60 mL/min/1.73 m^2. Actual body weight should be used for calculating creatinine clearance (e.g., using the Cockroft-Gault formula). For subjects with a Body Mass Index (BMI) > 30 kg/m^2, lean body weight should be used instead",
            "criterions": [
                {
                    "exact_snippets": "Calculated clearance >= 60 mL/min/1.73 m^2",
                    "criterion": "calculated clearance",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 60,
                                "unit": "mL/min/1.73 m^2"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Actual body weight should be used for calculating creatinine clearance",
                    "criterion": "creatinine clearance calculation weight",
                    "requirements": [
                        {
                            "requirement_type": "weight type",
                            "expected_value": "actual body weight"
                        }
                    ]
                },
                {
                    "exact_snippets": "For subjects with a Body Mass Index (BMI) > 30 kg/m^2, lean body weight should be used instead",
                    "criterion": "creatinine clearance calculation weight",
                    "requirements": [
                        {
                            "requirement_type": "weight type",
                            "expected_value": "lean body weight"
                        }
                    ]
                },
                {
                    "exact_snippets": "Body Mass Index (BMI) > 30 kg/m^2",
                    "criterion": "Body Mass Index (BMI)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">",
                                "value": 30,
                                "unit": "kg/m^2"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Total bilirubin =< 1.5 X upper limit of normal (ULN) (subjects with known Gilbert's hepatic function disease can have bilirubin of up to 2 X ULN)",
            "criterions": [
                {
                    "exact_snippets": "Total bilirubin =< 1.5 X upper limit of normal (ULN)",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "X ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "subjects with known Gilbert's hepatic function disease can have bilirubin of up to 2 X ULN",
                    "criterion": "total bilirubin in subjects with Gilbert's hepatic function disease",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "X ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 X ULN; or AST/ALT =< 5 X ULN if patient has liver tumors",
            "criterions": [
                {
                    "exact_snippets": "Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 X ULN",
                    "criterion": "AST/ALT levels",
                    "requirements": [
                        {
                            "requirement_type": "comparison",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "X ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "AST/ALT =< 5 X ULN if patient has liver tumors",
                    "criterion": "AST/ALT levels with liver tumors",
                    "requirements": [
                        {
                            "requirement_type": "comparison",
                            "expected_value": {
                                "operator": "<=",
                                "value": 5,
                                "unit": "X ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prothrombin time (PT)/international normalized ratio (INR) =< 1.8 times upper limit of normal (unless patient is on anticoagulation)",
            "criterions": [
                {
                    "exact_snippets": "Prothrombin time (PT)/international normalized ratio (INR) =< 1.8 times upper limit of normal",
                    "criterion": "Prothrombin time (PT)/international normalized ratio (INR)",
                    "requirements": [
                        {
                            "requirement_type": "comparison",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.8,
                                "unit": "times upper limit of normal"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "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": "* Patients who have had hypersensitivity to pentamidine or any excipients of AU409",
            "criterions": [
                {
                    "exact_snippets": "hypersensitivity to pentamidine",
                    "criterion": "hypersensitivity to pentamidine",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "hypersensitivity to ... excipients of AU409",
                    "criterion": "hypersensitivity to excipients of AU409",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Treatment with other anticancer therapies (including surgery, radiation therapy, chemotherapy, anti-angiogenic therapy, targeted therapy, or radiofrequency ablation therapy, etc.) or investigational therapy within 28 days prior to study entry (except for palliative radiation therapy that should be completed >= 14 days prior to study entry)",
            "criterions": [
                {
                    "exact_snippets": "Treatment with other anticancer therapies (including surgery, radiation therapy, chemotherapy, anti-angiogenic therapy, targeted therapy, or radiofrequency ablation therapy, etc.) or investigational therapy within 28 days prior to study entry",
                    "criterion": "treatment with other anticancer therapies or investigational therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": ">=",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "palliative radiation therapy that should be completed >= 14 days prior to study entry",
                    "criterion": "palliative radiation therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since completion",
                            "expected_value": {
                                "operator": ">=",
                                "value": 14,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Hepatocellular carcinoma patients with a Child Pugh score >= B7",
            "criterions": [
                {
                    "exact_snippets": "Hepatocellular carcinoma patients",
                    "criterion": "hepatocellular carcinoma",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Child Pugh score >= B7",
                    "criterion": "Child Pugh score",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 7,
                                "unit": "B"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with known central nervous system metastases which are untreated or symptomatic; patients with treated brain metastases (completed >= 30 days prior to screening) are allowed provided they are asymptomatic and are off steroids",
            "criterions": [
                {
                    "exact_snippets": "known central nervous system metastases",
                    "criterion": "central nervous system metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "untreated or symptomatic",
                    "criterion": "central nervous system metastases",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "untreated"
                        },
                        {
                            "requirement_type": "symptom status",
                            "expected_value": "symptomatic"
                        }
                    ]
                },
                {
                    "exact_snippets": "treated brain metastases (completed >= 30 days prior to screening)",
                    "criterion": "treated brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "treatment completion time",
                            "expected_value": {
                                "operator": ">=",
                                "value": 30,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "asymptomatic",
                    "criterion": "brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "symptom status",
                            "expected_value": "asymptomatic"
                        }
                    ]
                },
                {
                    "exact_snippets": "off steroids",
                    "criterion": "steroid use",
                    "requirements": [
                        {
                            "requirement_type": "usage",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patient with a history of the following within 6 months prior to cycle 1 day 1: a myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) Class III-IV heart failure, uncontrolled hypertension, clinically significant cardiac dysrhythmia, cerebrovascular accident, transient ischemic attack, or seizure disorder. Atrial fibrillation is allowed if rate is controlled",
            "criterions": [
                {
                    "exact_snippets": "history of ... myocardial infarction",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "history of ... severe/unstable angina pectoris",
                    "criterion": "severe/unstable angina pectoris",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "history of ... coronary/peripheral artery bypass graft",
                    "criterion": "coronary/peripheral artery bypass graft",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "history of ... New York Heart Association (NYHA) Class III-IV heart failure",
                    "criterion": "New York Heart Association (NYHA) Class III-IV heart failure",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "history of ... uncontrolled hypertension",
                    "criterion": "uncontrolled hypertension",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "history of ... clinically significant cardiac dysrhythmia",
                    "criterion": "clinically significant cardiac dysrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "history of ... cerebrovascular accident",
                    "criterion": "cerebrovascular accident",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "history of ... transient ischemic attack",
                    "criterion": "transient ischemic attack",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "history of ... seizure disorder",
                    "criterion": "seizure disorder",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Atrial fibrillation ... rate is controlled",
                    "criterion": "atrial fibrillation",
                    "requirements": [
                        {
                            "requirement_type": "rate control",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who have corrected QT (QTc) interval to > 470 msec (Fredericia's equation) on 2 out of 3 electrocardiogram (ECG)'s (if first ECG has QTc < 470, no need to repeat, if first ECG has QTc > 470 repeat twice for a total of 3 ECG's)",
            "criterions": [
                {
                    "exact_snippets": "corrected QT (QTc) interval to > 470 msec (Fredericia's equation)",
                    "criterion": "corrected QT (QTc) interval",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">",
                                "value": 470,
                                "unit": "msec"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who are on therapeutic anticoagulation with warfarin; however, patients on therapeutic doses of with low molecular weight heparins or Factor Xa inhibitors are eligible",
            "criterions": [
                {
                    "exact_snippets": "Patients who are on therapeutic anticoagulation with warfarin",
                    "criterion": "therapeutic anticoagulation with warfarin",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "patients on therapeutic doses of with low molecular weight heparins or Factor Xa inhibitors are eligible",
                    "criterion": "therapeutic doses of low molecular weight heparins or Factor Xa inhibitors",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patient with history of gastrointestinal surgery or malabsorptive conditions that may change the absorption of drugs and/or cause rapid transit (such as total gastrectomy, small bowel resection, etc.)",
            "criterions": [
                {
                    "exact_snippets": "history of gastrointestinal surgery",
                    "criterion": "gastrointestinal surgery history",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "malabsorptive conditions",
                    "criterion": "malabsorptive conditions",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who have known active hepatitis B. Patients with chronic hepatitis B who are on anti-viral therapy and have a hepatitis B viral load of =< 500 IU/mL are allowed on the study. Patients with chronic Hepatitis C are allowed",
            "criterions": [
                {
                    "exact_snippets": "known active hepatitis B",
                    "criterion": "active hepatitis B",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "chronic hepatitis B ... on anti-viral therapy",
                    "criterion": "chronic hepatitis B",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": "anti-viral therapy"
                        }
                    ]
                },
                {
                    "exact_snippets": "chronic hepatitis B ... hepatitis B viral load of =< 500 IU/mL",
                    "criterion": "hepatitis B viral load",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 500,
                                "unit": "IU/mL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "chronic Hepatitis C",
                    "criterion": "chronic Hepatitis C",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who have active infection requiring treatment (except hepatitis B and C as noted above) including known human immunodeficiency virus (HIV) infection",
            "criterions": [
                {
                    "exact_snippets": "active infection requiring treatment",
                    "criterion": "active infection",
                    "requirements": [
                        {
                            "requirement_type": "treatment requirement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "known human immunodeficiency virus (HIV) infection",
                    "criterion": "HIV infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who have concurrent conditions resulting in immune compromise, including chronic treatment with corticosteroids or other immunosuppressive agents",
            "criterions": [
                {
                    "exact_snippets": "concurrent conditions resulting in immune compromise",
                    "criterion": "immune compromise",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "chronic treatment with corticosteroids",
                    "criterion": "corticosteroid treatment",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "chronic"
                        }
                    ]
                },
                {
                    "exact_snippets": "chronic treatment with ... other immunosuppressive agents",
                    "criterion": "immunosuppressive agent treatment",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "chronic"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who have any other condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results",
            "criterions": [
                {
                    "exact_snippets": "any other condition, including mental illness or substance abuse",
                    "criterion": "other condition",
                    "requirements": [
                        {
                            "requirement_type": "interference with ability to sign informed consent",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "any other condition, including mental illness or substance abuse",
                    "criterion": "other condition",
                    "requirements": [
                        {
                            "requirement_type": "interference with ability to cooperate and participate in the study",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "any other condition, including mental illness or substance abuse",
                    "criterion": "other condition",
                    "requirements": [
                        {
                            "requirement_type": "interference with the interpretation of the results",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants",
            "criterions": [
                {
                    "exact_snippets": "Patients must not be pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "not be ... nursing",
                    "criterion": "nursing",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who are on medications that are considered to be strong inducers or inhibitors of the cytochrome P450 isoenzymes should have such medications discontinued or replaced. Such medications should be avoided for one week prior to first dose of treatment and during the trial participation. If these medications are absolutely necessary for the patient and cannot be replaced, enrollment may still be considered on a case by case basis if it is in the patient's best interest and after discussion with the principal investigator (PI)",
            "criterions": [
                {
                    "exact_snippets": "Patients who are on medications that are considered to be strong inducers or inhibitors of the cytochrome P450 isoenzymes",
                    "criterion": "medications affecting cytochrome P450 isoenzymes",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "medications should be avoided for one week prior to first dose of treatment and during the trial participation",
                    "criterion": "medications affecting cytochrome P450 isoenzymes",
                    "requirements": [
                        {
                            "requirement_type": "avoidance period",
                            "expected_value": "one week prior to first dose and during trial"
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}