{
    "info": {
        "nct_id": "NCT02241720",
        "official_title": "Regorafenib as a Second Line Single Agent in the Treatment of Metastatic or Advanced Adenocarcinoma of the Esophagus, Gastroesophageal Junction or Stomach",
        "inclusion_criteria": "* Histological diagnosis of metastatic or locally advanced inoperable adenocarcinoma of the esophagus, gastroesophageal junction or stomach.\n* Patients must show signs of progression during or less than 4 months after being treated with a first line therapy for their metastatic or locally advanced inoperable cancer.\n* Patients must have measureable disease at screening by Response Evaluation Criteria for Solid Tumors 1.1 criteria\n* Age greater than or equal to 18 years.\n* Eastern Cooperative Oncology Group Performance Status 0-1\n* Subjects must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure.\n* All acute toxic effects of any prior treatment have resolved to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 Grade 1 or less at the time of signing the Informed Consent Form. Alopecia (any grade) and peripheral neuropathy less than grade 2 is allowed.\n* Adequate bone marrow, liver and liver function as assessed by laboratory requirement\n* Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug. Post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test.\n* Subjects (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the informed consent form until at least 3 months after the last dose of study drug. Highly effective contraception must be used (male condom with spermicidal, diaphragm with spermicidal, intra-uterine device) by both sexes.\n* Subject must be able to swallow and retain oral medication.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Prior use of regorafenib\n* Uncontrolled hypertension (systolic pressure greater than 140 mm Hg or diastolic pressure greater than 90 mm Hg National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 on repeated measurement) despite optimal medical management.\n* Active or clinically significant cardiac disease including:\n* Congestive heart failure - New York Heart Association greater than Class 2.\n* Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers.\n* Unstable angina (anginal symptoms at rest), new-onset angina within 3 months before randomization, or myocardial infarction within 6 months before randomization.\n* Evidence or history of bleeding diathesis or coagulopathy.\n* Any hemorrhage or bleeding event greater than or equal to National Cancer Institute Common Terminology Criteria for Adverse Events Grade 3 within 4 weeks prior to start of study medication.\n* Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks) deep vein thrombosis or pulmonary embolism within 6 months of start of study treatment\n* Subjects with any previously untreated or concurrent cancer that is distinct in primary site or histology except cervical cancer in-situ, treated basal cell carcinoma, or superficial bladder tumor. Subjects surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before randomization are allowed. All cancer treatments must be completed at least 3 years prior to start of study treatment.\n* Patients with severe hepatic impairment (Child-Pugh Class C)\n* Known history of human immunodeficiency virus infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy.\n* Patients requiring intravenous antiviral or intravenous antibiotic treatment for ongoing infections\n* Symptomatic metastatic brain or meningeal tumors.\n* Presence of a non-healing wound, non-healing skin ulcer, or bone fracture.\n* Patient's with a history of kidney disease or persistent proteinuria must have less than Grade 3 proteinuria per NCI CTCAE v4.0 at screening. If a patient has a history of kidney disease or persistent proteinuria, a urine protein test will be performed on a random urine sample. If the result is normal then no additional testing is required. If the result is abnormal, a 24 hour urine will be collected to determine if proteinuria is less than Grade 3.\n* Interstitial lung disease with ongoing signs and symptoms at the time of informed consent.\n* Pleural effusion or ascites that causes respiratory compromise (greater than or equal to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 Grade 2 dyspnea). Patients may undergo thoracentesis and paracentesis to improve symptoms prior to enrollment.\n* History of organ allograft (including corneal transplant).\n* Known or suspected grade 3 allergy or hypersensitivity to any of the study drugs, study drug classes, or excipients of the formulations given during the course of this trial.\n* Any malabsorption condition that in the opinion of the investigator would significantly impact drug absorption.\n* Women who are pregnant or breast-feeding.\n* Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.\n* Substance abuse, medical, psychological or social conditions that in the opinion of the investigator may interfere with the subject's participation in the study or evaluation of the study results.\n* Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) within 28 days of starting study treatment. Palliative radiation is allowed.\n* Concurrent use of another investigational drug or device during, or within 3 weeks of starting study treatment.\n* Concurrent use of strong CYP3A4 inducers (e.g. rifampin, phenytoin, carbamazepine, phenobarbital, and St. John's Wort)\n* Concurrent use with strong inhibitors of CYP3A4 (e.g. clarithromycin, grapefruit juice, itraconazole, ketoconazole, nefazadone, posaconazole, telithromycin, and voriconazole)\n* Major surgical procedure, open biopsy, or significant traumatic injury within 3 weeks before start of study medication.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Histological diagnosis of metastatic or locally advanced inoperable adenocarcinoma of the esophagus, gastroesophageal junction or stomach.",
            "criterions": [
                {
                    "exact_snippets": "Histological diagnosis of metastatic or locally advanced inoperable adenocarcinoma",
                    "criterion": "adenocarcinoma",
                    "requirements": [
                        {
                            "requirement_type": "diagnosis",
                            "expected_value": "histological"
                        },
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "metastatic",
                                "locally advanced inoperable"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "adenocarcinoma of the esophagus, gastroesophageal junction or stomach",
                    "criterion": "location of adenocarcinoma",
                    "requirements": [
                        {
                            "requirement_type": "location",
                            "expected_value": [
                                "esophagus",
                                "gastroesophageal junction",
                                "stomach"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must show signs of progression during or less than 4 months after being treated with a first line therapy for their metastatic or locally advanced inoperable cancer.",
            "criterions": [
                {
                    "exact_snippets": "signs of progression",
                    "criterion": "signs of progression",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "less than 4 months after being treated",
                    "criterion": "time since treatment",
                    "requirements": [
                        {
                            "requirement_type": "time since treatment",
                            "expected_value": {
                                "operator": "<",
                                "value": 4,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "first line therapy",
                    "criterion": "first line therapy",
                    "requirements": [
                        {
                            "requirement_type": "treatment type",
                            "expected_value": "first line therapy"
                        }
                    ]
                },
                {
                    "exact_snippets": "metastatic or locally advanced inoperable cancer",
                    "criterion": "cancer type",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "metastatic",
                                "locally advanced inoperable"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must have measureable disease at screening by Response Evaluation Criteria for Solid Tumors 1.1 criteria",
            "criterions": [
                {
                    "exact_snippets": "measureable disease at screening",
                    "criterion": "disease measurability",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Response Evaluation Criteria for Solid Tumors 1.1 criteria",
                    "criterion": "RECIST 1.1 criteria",
                    "requirements": [
                        {
                            "requirement_type": "compliance",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Age greater than or equal to 18 years.",
            "criterions": [
                {
                    "exact_snippets": "Age greater than or equal to 18 years.",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Eastern Cooperative Oncology Group Performance Status 0-1",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group Performance Status 0-1",
                    "criterion": "Eastern Cooperative Oncology Group Performance Status",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 1,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Subjects must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure.",
            "criterions": [
                {
                    "exact_snippets": "Subjects must be able to understand",
                    "criterion": "understanding ability",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "be willing to sign the written informed consent form",
                    "criterion": "willingness to sign consent",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "A signed informed consent form must be appropriately obtained",
                    "criterion": "signed informed consent form",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* All acute toxic effects of any prior treatment have resolved to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 Grade 1 or less at the time of signing the Informed Consent Form. Alopecia (any grade) and peripheral neuropathy less than grade 2 is allowed.",
            "criterions": [
                {
                    "exact_snippets": "All acute toxic effects of any prior treatment have resolved to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 Grade 1 or less",
                    "criterion": "acute toxic effects of prior treatment",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "NCI CTCAE v4.0 Grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Alopecia (any grade)",
                    "criterion": "alopecia",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "any grade"
                        }
                    ]
                },
                {
                    "exact_snippets": "peripheral neuropathy less than grade 2",
                    "criterion": "peripheral neuropathy",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<",
                                "value": 2,
                                "unit": "grade"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate bone marrow, liver and liver function as assessed by laboratory requirement",
            "criterions": [
                {
                    "exact_snippets": "Adequate bone marrow",
                    "criterion": "bone marrow",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate ... liver",
                    "criterion": "liver",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate ... liver function",
                    "criterion": "liver function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug. Post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test.",
            "criterions": [
                {
                    "exact_snippets": "Women of childbearing potential must have a negative serum pregnancy test",
                    "criterion": "serum pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "performed within 7 days prior to the start of study drug",
                    "criterion": "timing of serum pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "within 7 days prior to the start of study drug"
                        }
                    ]
                },
                {
                    "exact_snippets": "Post-menopausal women (defined as no menses for at least 1 year)",
                    "criterion": "post-menopausal status",
                    "requirements": [
                        {
                            "requirement_type": "definition",
                            "expected_value": "no menses for at least 1 year"
                        }
                    ]
                },
                {
                    "exact_snippets": "surgically sterilized women",
                    "criterion": "surgical sterilization",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Subjects (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the informed consent form until at least 3 months after the last dose of study drug. Highly effective contraception must be used (male condom with spermicidal, diaphragm with spermicidal, intra-uterine device) by both sexes.",
            "criterions": [
                {
                    "exact_snippets": "Subjects (men and women) of childbearing potential",
                    "criterion": "childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "must agree to use adequate contraception",
                    "criterion": "contraception agreement",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "beginning at the signing of the informed consent form until at least 3 months after the last dose of study drug",
                    "criterion": "contraception duration",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "from signing of informed consent until at least 3 months after last dose"
                        }
                    ]
                },
                {
                    "exact_snippets": "Highly effective contraception must be used (male condom with spermicidal, diaphragm with spermicidal, intra-uterine device) by both sexes",
                    "criterion": "contraception method",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": [
                                "male condom with spermicidal",
                                "diaphragm with spermicidal",
                                "intra-uterine device"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Subject must be able to swallow and retain oral medication.",
            "criterions": [
                {
                    "exact_snippets": "Subject must be able to swallow",
                    "criterion": "ability to swallow",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "retain oral medication",
                    "criterion": "ability to retain oral medication",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have minimum age of 18 Years",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 18 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "* Prior use of regorafenib",
            "criterions": [
                {
                    "exact_snippets": "Prior use of regorafenib",
                    "criterion": "regorafenib use",
                    "requirements": [
                        {
                            "requirement_type": "prior use",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Uncontrolled hypertension (systolic pressure greater than 140 mm Hg or diastolic pressure greater than 90 mm Hg National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 on repeated measurement) despite optimal medical management.",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled hypertension (systolic pressure greater than 140 mm Hg ... despite optimal medical management",
                    "criterion": "hypertension",
                    "requirements": [
                        {
                            "requirement_type": "control status",
                            "expected_value": "uncontrolled"
                        },
                        {
                            "requirement_type": "systolic pressure",
                            "expected_value": {
                                "operator": ">",
                                "value": 140,
                                "unit": "mm Hg"
                            }
                        },
                        {
                            "requirement_type": "diastolic pressure",
                            "expected_value": {
                                "operator": ">",
                                "value": 90,
                                "unit": "mm Hg"
                            }
                        },
                        {
                            "requirement_type": "medical management",
                            "expected_value": "optimal"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Active or clinically significant cardiac disease including:",
            "criterions": [
                {
                    "exact_snippets": "Active or clinically significant cardiac disease",
                    "criterion": "cardiac disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "clinical significance",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Congestive heart failure - New York Heart Association greater than Class 2.",
            "criterions": [
                {
                    "exact_snippets": "Congestive heart failure - New York Heart Association greater than Class 2.",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">",
                                "value": 2,
                                "unit": "New York Heart Association Class"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers.",
            "criterions": [
                {
                    "exact_snippets": "Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers.",
                    "criterion": "cardiac arrhythmias",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": "anti-arrhythmic therapy other than beta blockers"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Unstable angina (anginal symptoms at rest), new-onset angina within 3 months before randomization, or myocardial infarction within 6 months before randomization.",
            "criterions": [
                {
                    "exact_snippets": "Unstable angina (anginal symptoms at rest)",
                    "criterion": "unstable angina",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "new-onset angina within 3 months before randomization",
                    "criterion": "new-onset angina",
                    "requirements": [
                        {
                            "requirement_type": "timeframe",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "myocardial infarction within 6 months before randomization",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "timeframe",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Evidence or history of bleeding diathesis or coagulopathy.",
            "criterions": [
                {
                    "exact_snippets": "Evidence or history of bleeding diathesis",
                    "criterion": "bleeding diathesis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Evidence or history of ... coagulopathy",
                    "criterion": "coagulopathy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any hemorrhage or bleeding event greater than or equal to National Cancer Institute Common Terminology Criteria for Adverse Events Grade 3 within 4 weeks prior to start of study medication.",
            "criterions": [
                {
                    "exact_snippets": "Any hemorrhage or bleeding event",
                    "criterion": "hemorrhage or bleeding event",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "NCI CTCAE Grade"
                            }
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 4 weeks prior to start of study medication"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks) deep vein thrombosis or pulmonary embolism within 6 months of start of study treatment",
            "criterions": [
                {
                    "exact_snippets": "thrombotic, embolic, venous, or arterial events",
                    "criterion": "thrombotic, embolic, venous, or arterial events",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "cerebrovascular accident (including transient ischemic attacks)",
                    "criterion": "cerebrovascular accident",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "deep vein thrombosis",
                    "criterion": "deep vein thrombosis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "pulmonary embolism",
                    "criterion": "pulmonary embolism",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "within 6 months of start of study treatment",
                    "criterion": "time since event",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Subjects with any previously untreated or concurrent cancer that is distinct in primary site or histology except cervical cancer in-situ, treated basal cell carcinoma, or superficial bladder tumor. Subjects surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before randomization are allowed. All cancer treatments must be completed at least 3 years prior to start of study treatment.",
            "criterions": [
                {
                    "exact_snippets": "any previously untreated or concurrent cancer that is distinct in primary site or histology",
                    "criterion": "previously untreated or concurrent cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "except cervical cancer in-situ, treated basal cell carcinoma, or superficial bladder tumor",
                    "criterion": "specific cancer types",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": [
                                "cervical cancer in-situ",
                                "treated basal cell carcinoma",
                                "superficial bladder tumor"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Subjects surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before randomization",
                    "criterion": "cancer-free duration",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 3,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "All cancer treatments must be completed at least 3 years prior to start of study treatment",
                    "criterion": "completion of cancer treatments",
                    "requirements": [
                        {
                            "requirement_type": "completion time",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with severe hepatic impairment (Child-Pugh Class C)",
            "criterions": [
                {
                    "exact_snippets": "severe hepatic impairment (Child-Pugh Class C)",
                    "criterion": "hepatic impairment",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        },
                        {
                            "requirement_type": "classification",
                            "expected_value": "Child-Pugh Class C"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Known history of human immunodeficiency virus infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy.",
            "criterions": [
                {
                    "exact_snippets": "Known history of human immunodeficiency virus infection",
                    "criterion": "human immunodeficiency virus infection",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy",
                    "criterion": "hepatitis B or C infection",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "current chronic or active"
                        },
                        {
                            "requirement_type": "treatment",
                            "expected_value": "requiring antiviral therapy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients requiring intravenous antiviral or intravenous antibiotic treatment for ongoing infections",
            "criterions": [
                {
                    "exact_snippets": "Patients requiring intravenous antiviral ... treatment for ongoing infections",
                    "criterion": "intravenous antiviral treatment",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients requiring ... intravenous antibiotic treatment for ongoing infections",
                    "criterion": "intravenous antibiotic treatment",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Symptomatic metastatic brain or meningeal tumors.",
            "criterions": [
                {
                    "exact_snippets": "Symptomatic metastatic brain",
                    "criterion": "metastatic brain tumors",
                    "requirements": [
                        {
                            "requirement_type": "symptomatic",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Symptomatic ... meningeal tumors",
                    "criterion": "meningeal tumors",
                    "requirements": [
                        {
                            "requirement_type": "symptomatic",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Presence of a non-healing wound, non-healing skin ulcer, or bone fracture.",
            "criterions": [
                {
                    "exact_snippets": "Presence of a non-healing wound",
                    "criterion": "non-healing wound",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Presence of a ... non-healing skin ulcer",
                    "criterion": "non-healing skin ulcer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Presence of a ... bone fracture",
                    "criterion": "bone fracture",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patient's with a history of kidney disease or persistent proteinuria must have less than Grade 3 proteinuria per NCI CTCAE v4.0 at screening. If a patient has a history of kidney disease or persistent proteinuria, a urine protein test will be performed on a random urine sample. If the result is normal then no additional testing is required. If the result is abnormal, a 24 hour urine will be collected to determine if proteinuria is less than Grade 3.",
            "criterions": [
                {
                    "exact_snippets": "history of kidney disease",
                    "criterion": "history of kidney disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "persistent proteinuria",
                    "criterion": "persistent proteinuria",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "less than Grade 3 proteinuria per NCI CTCAE v4.0",
                    "criterion": "proteinuria grade",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<",
                                "value": 3,
                                "unit": "Grade"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Interstitial lung disease with ongoing signs and symptoms at the time of informed consent.",
            "criterions": [
                {
                    "exact_snippets": "Interstitial lung disease with ongoing signs and symptoms",
                    "criterion": "interstitial lung disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "symptoms",
                            "expected_value": "ongoing"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Pleural effusion or ascites that causes respiratory compromise (greater than or equal to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 Grade 2 dyspnea). Patients may undergo thoracentesis and paracentesis to improve symptoms prior to enrollment.",
            "criterions": [
                {
                    "exact_snippets": "Pleural effusion or ascites that causes respiratory compromise (greater than or equal to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 Grade 2 dyspnea)",
                    "criterion": "pleural effusion or ascites",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": ">= National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 Grade 2 dyspnea"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of organ allograft (including corneal transplant).",
            "criterions": [
                {
                    "exact_snippets": "History of organ allograft",
                    "criterion": "organ allograft",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "corneal transplant",
                    "criterion": "corneal transplant",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Known or suspected grade 3 allergy or hypersensitivity to any of the study drugs, study drug classes, or excipients of the formulations given during the course of this trial.",
            "criterions": [
                {
                    "exact_snippets": "Known or suspected grade 3 allergy or hypersensitivity to any of the study drugs",
                    "criterion": "allergy or hypersensitivity",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "grade 3"
                        },
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "allergy or hypersensitivity to ... study drug classes",
                    "criterion": "allergy or hypersensitivity",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "allergy or hypersensitivity to ... excipients of the formulations",
                    "criterion": "allergy or hypersensitivity",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any malabsorption condition that in the opinion of the investigator would significantly impact drug absorption.",
            "criterions": [
                {
                    "exact_snippets": "Any malabsorption condition ... would significantly impact drug absorption.",
                    "criterion": "malabsorption condition",
                    "requirements": [
                        {
                            "requirement_type": "impact on drug absorption",
                            "expected_value": "significant"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Women who are pregnant or breast-feeding.",
            "criterions": [
                {
                    "exact_snippets": "Women who are pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "breast-feeding",
                    "criterion": "breast-feeding",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.",
            "criterions": [
                {
                    "exact_snippets": "Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.",
                    "criterion": "suitability for trial participation",
                    "requirements": [
                        {
                            "requirement_type": "opinion",
                            "expected_value": "investigator's opinion"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Substance abuse, medical, psychological or social conditions that in the opinion of the investigator may interfere with the subject's participation in the study or evaluation of the study results.",
            "criterions": [
                {
                    "exact_snippets": "Substance abuse",
                    "criterion": "substance abuse",
                    "requirements": [
                        {
                            "requirement_type": "interference with study participation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "medical ... conditions",
                    "criterion": "medical conditions",
                    "requirements": [
                        {
                            "requirement_type": "interference with study participation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "psychological ... conditions",
                    "criterion": "psychological conditions",
                    "requirements": [
                        {
                            "requirement_type": "interference with study participation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "social conditions",
                    "criterion": "social conditions",
                    "requirements": [
                        {
                            "requirement_type": "interference with study participation",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) within 28 days of starting study treatment. Palliative radiation is allowed.",
            "criterions": [
                {
                    "exact_snippets": "Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) within 28 days of starting study treatment.",
                    "criterion": "concurrent anti-cancer therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Palliative radiation is allowed.",
                    "criterion": "palliative radiation",
                    "requirements": [
                        {
                            "requirement_type": "allowance",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Concurrent use of another investigational drug or device during, or within 3 weeks of starting study treatment.",
            "criterions": [
                {
                    "exact_snippets": "Concurrent use of another investigational drug",
                    "criterion": "use of another investigational drug",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Concurrent use of another investigational ... device",
                    "criterion": "use of another investigational device",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "within 3 weeks of starting study treatment",
                    "criterion": "time since last investigational drug or device use",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": "<",
                                "value": 3,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Concurrent use of strong CYP3A4 inducers (e.g. rifampin, phenytoin, carbamazepine, phenobarbital, and St. John's Wort)",
            "criterions": [
                {
                    "exact_snippets": "Concurrent use of strong CYP3A4 inducers (e.g. rifampin, phenytoin, carbamazepine, phenobarbital, and St. John's Wort)",
                    "criterion": "use of strong CYP3A4 inducers",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Concurrent use with strong inhibitors of CYP3A4 (e.g. clarithromycin, grapefruit juice, itraconazole, ketoconazole, nefazadone, posaconazole, telithromycin, and voriconazole)",
            "criterions": [
                {
                    "exact_snippets": "Concurrent use with strong inhibitors of CYP3A4 (e.g. clarithromycin, grapefruit juice, itraconazole, ketoconazole, nefazadone, posaconazole, telithromycin, and voriconazole)",
                    "criterion": "use of strong CYP3A4 inhibitors",
                    "requirements": [
                        {
                            "requirement_type": "concurrent use",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Major surgical procedure, open biopsy, or significant traumatic injury within 3 weeks before start of study medication.",
            "criterions": [
                {
                    "exact_snippets": "Major surgical procedure, open biopsy, or significant traumatic injury within 3 weeks before start of study medication.",
                    "criterion": "major surgical procedure",
                    "requirements": [
                        {
                            "requirement_type": "time since occurrence",
                            "expected_value": {
                                "operator": "<",
                                "value": 3,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Major surgical procedure, open biopsy, or significant traumatic injury within 3 weeks before start of study medication.",
                    "criterion": "open biopsy",
                    "requirements": [
                        {
                            "requirement_type": "time since occurrence",
                            "expected_value": {
                                "operator": "<",
                                "value": 3,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Major surgical procedure, open biopsy, or significant traumatic injury within 3 weeks before start of study medication.",
                    "criterion": "significant traumatic injury",
                    "requirements": [
                        {
                            "requirement_type": "time since occurrence",
                            "expected_value": {
                                "operator": "<",
                                "value": 3,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}