{
    "info": {
        "nct_id": "NCT01664182",
        "official_title": "A Randomized Phase 2 Study of AMG 386 With or Without Continued Anti-Vascular Endothelial Growth Factor (VEGF) Therapy in Patients With Renal Cell Carcinoma Who Have Progressed on Bevacizumab, Pazopanib, Sorafenib, or Sunitinib",
        "inclusion_criteria": "* Patients must have histologically or cytologically confirmed renal cell carcinoma except medullary or collecting duct subtypes; sarcomatoid differentiation will be allowed\n* Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam\n* Patients must have documented radiologic or clinical progressive disease following at least one prior anti-VEGF regimen administered either as a single agent or in combination with other agents for at least 8 weeks; the prior anti-VEGF treatment regimen must have included bevacizumab, pazopanib, sorafenib or sunitinib administered not more than 12 weeks before study entry; Note: enrollment not more than 8 weeks after the last dose of anti-VEGF therapy is encouraged; nevertheless, intercurrent therapy with an mTOR inhibitor (everolimus or temsirolimus) will be allowed if progression on that treatment is observed within 12 weeks of the prior anti-VEGF therapy\n* Any number of prior regimens is allowed; prior investigational therapy is allowed\n* Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)\n* Life expectancy of greater than 3 months\n* Leukocytes >= 3,000/mcL\n* Absolute neutrophil count >= 1,500/mcL\n* Platelets >= 100,000/mcL\n* Total bilirubin =< institutional upper limits of normal\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal\n* Partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) =< upper limit of normal (ULN) per institutional laboratory range\n* International normalized ratio (INR) =< 1.5\n* Creatinine within normal institutional limits OR creatinine clearance > 40 mL/min per 24 hour (h) urine collection or calculated according to the Cockcroft-Gault formula\n* Urinary protein =< 100 mg/dL in urinalysis or =< 1+ on dipstick, unless quantitative protein is < 1000 mg in a 24 h urine sample\n* Generally well-controlled blood pressure with systolic blood pressure =< 140 mmHg AND diastolic blood pressure =< 90 mmHg prior to enrollment; the use of anti-hypertensive medications to control hypertension is permitted\n* Patients must have a tumor site amenable to biopsy as determined by the treating investigator; any questions regarding suitability of a site for biopsy will be adjudicated by the principal investigator\n* Patients must be willing to consent to tumor biopsy for research purposes\n* Patients should have archival tumor tissue (either unstained slides or tumor blocks) available for retrieval\n* The effects of AMG 386 are known to be detrimental to fetal development; for this reason and because inhibitors of angiogenesis as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential 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, and 6 months after completion of AMG 386; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of AMG 386 and bevacizumab, pazopanib, sunitinib, or sorafenib administration\n* Ability to understand and the willingness to sign a written informed consent document\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Intolerance of prior treatment with bevacizumab, pazopanib, sorafenib, or sunitinib; Note: subjects who required a dose reduction of pazopanib, sorafenib, or sunitinib during prior therapy MAY be eligible if they tolerated the agent after dose level reduction (to a minimum of dose level -2 as defined in this protocol)\n* Central nervous system metastases unless: (1) metastases have been treated and have remained controlled for at least two weeks following treatment, AND (2) patient has no residual neurological dysfunction off corticosteroids for at least one week; a CT or MRI to evaluate for central nervous system (CNS) disease is required for symptomatic patients only\n* History of venous or arterial thromboembolism within 12 months prior to enrollment/randomization\n* History of clinically significant bleeding within 6 months of enrollment/randomization\n* Unresolved toxicities from prior systemic therapy that are Common Terminology Criteria in Adverse Events (CTCAE) version 3.0 or 4.0 >= grade 2 in severity except alopecia\n* Currently or previously treated with AMG 386, or other molecules that inhibit the angiopoietins or Tie2 receptor\n* Clinically significant cardiovascular disease within 12 months prior to enrollment/randomization, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication or placement of percutaneous transluminal coronary angioplasty/stent\n* Major surgery within 28 days prior to enrollment or still recovering from prior surgery\n* Minor surgical procedures except placement of tunneled central venous access device within 3 days prior to enrollment\n* Non-healing wound, ulcer (including gastrointestinal), or fracture\n* Subject not consenting to the use of highly effective contraceptive precautions (e.g., double barrier method [i.e., condom plus diaphragm]) during the course of the study and for 6 months after administration of the last study medication\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to AMG 386 or the anti-VEGF agent used in study\n* History of allergic reactions to bacterially-produced proteins\n* Patients who have had anti-VEGFR tyrosine kinase inhibitor within 1 week, mTOR inhibitor within 1 week or anti-VEGF antibody therapy within 3 weeks prior to entering the study; patients who have had other forms of chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier\n* Patients who have not yet completed at least 21 days (30 days for prior monoclonal antibody therapy) since ending other investigational device or drug trials, or who are currently receiving other investigational treatments\n* Patients receiving any medications or substances that are strong inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP450 3A4) are ineligible; caution is advised for patients requiring weak or moderate CYP450 3A4 inhibitors or inducers; specifically prohibited medicines include indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, nefazodone, carbamazepine, phenobarbital, phenytoin, pioglitazone, rifabutin, rifampin, St. John's wort, and troglitazone\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements\n* Pregnant women are excluded from this study because AMG 386, bevacizumab, pazopanib, sorafenib, and sunitinib are inhibitors of angiogenesis with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AMG 386, breastfeeding must be discontinued if the mother is treated with AMG 386\n* Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with pazopanib, sorafenib, or sunitinib; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated\n* Inability to take oral medications on a continuous basis; patients who are to take pazopanib, sorafenib, or sunitinib and are unable to swallow pills whole are ineligible (the pills cannot be crushed or broken)\n* Any condition which in the investigator's opinion makes the subject unsuitable for study participation",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Patients must have histologically or cytologically confirmed renal cell carcinoma except medullary or collecting duct subtypes; sarcomatoid differentiation will be allowed",
            "criterions": [
                {
                    "exact_snippets": "histologically or cytologically confirmed renal cell carcinoma",
                    "criterion": "renal cell carcinoma",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "except medullary or collecting duct subtypes",
                    "criterion": "renal cell carcinoma subtype",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": [
                                "medullary",
                                "collecting duct"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "sarcomatoid differentiation will be allowed",
                    "criterion": "sarcomatoid differentiation",
                    "requirements": [
                        {
                            "requirement_type": "allowance",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam",
            "criterions": [
                {
                    "exact_snippets": "measurable disease, defined as at least one lesion that can be accurately measured",
                    "criterion": "measurable disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "at least one lesion that can be accurately measured in at least one dimension",
                    "criterion": "lesion",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "lesion"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions",
                    "criterion": "lesion measurement",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": [
                                "longest diameter for non-nodal lesions",
                                "short axis for nodal lesions"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "as >= 20 mm with conventional techniques",
                    "criterion": "lesion size with conventional techniques",
                    "requirements": [
                        {
                            "requirement_type": "size",
                            "expected_value": {
                                "operator": ">=",
                                "value": 20,
                                "unit": "mm"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam",
                    "criterion": "lesion size with advanced imaging",
                    "requirements": [
                        {
                            "requirement_type": "size",
                            "expected_value": {
                                "operator": ">=",
                                "value": 10,
                                "unit": "mm"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must have documented radiologic or clinical progressive disease following at least one prior anti-VEGF regimen administered either as a single agent or in combination with other agents for at least 8 weeks; the prior anti-VEGF treatment regimen must have included bevacizumab, pazopanib, sorafenib or sunitinib administered not more than 12 weeks before study entry; Note: enrollment not more than 8 weeks after the last dose of anti-VEGF therapy is encouraged; nevertheless, intercurrent therapy with an mTOR inhibitor (everolimus or temsirolimus) will be allowed if progression on that treatment is observed within 12 weeks of the prior anti-VEGF therapy",
            "criterions": [
                {
                    "exact_snippets": "documented radiologic or clinical progressive disease",
                    "criterion": "progressive disease",
                    "requirements": [
                        {
                            "requirement_type": "documentation",
                            "expected_value": [
                                "radiologic",
                                "clinical"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "following at least one prior anti-VEGF regimen",
                    "criterion": "prior anti-VEGF regimen",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "regimen"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "the prior anti-VEGF treatment regimen must have included bevacizumab, pazopanib, sorafenib or sunitinib",
                    "criterion": "anti-VEGF treatment regimen",
                    "requirements": [
                        {
                            "requirement_type": "inclusion",
                            "expected_value": [
                                "bevacizumab",
                                "pazopanib",
                                "sorafenib",
                                "sunitinib"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "administered not more than 12 weeks before study entry",
                    "criterion": "anti-VEGF treatment regimen timing",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": {
                                "operator": "<=",
                                "value": 12,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "enrollment not more than 8 weeks after the last dose of anti-VEGF therapy",
                    "criterion": "enrollment timing",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": {
                                "operator": "<=",
                                "value": 8,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "intercurrent therapy with an mTOR inhibitor (everolimus or temsirolimus) will be allowed if progression on that treatment is observed within 12 weeks of the prior anti-VEGF therapy",
                    "criterion": "intercurrent mTOR inhibitor therapy",
                    "requirements": [
                        {
                            "requirement_type": "allowance",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "progression timing",
                            "expected_value": {
                                "operator": "<=",
                                "value": 12,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any number of prior regimens is allowed; prior investigational therapy is allowed",
            "criterions": [
                {
                    "exact_snippets": "Any number of prior regimens is allowed",
                    "criterion": "prior regimens",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": "any number"
                        }
                    ]
                },
                {
                    "exact_snippets": "prior investigational therapy is allowed",
                    "criterion": "prior investigational therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) performance status =< 1",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Karnofsky >= 70%",
                    "criterion": "Karnofsky performance status",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 70,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Life expectancy of greater than 3 months",
            "criterions": [
                {
                    "exact_snippets": "Life expectancy of greater than 3 months",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Leukocytes >= 3,000/mcL",
            "criterions": [
                {
                    "exact_snippets": "Leukocytes >= 3,000/mcL",
                    "criterion": "leukocytes",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3000,
                                "unit": "mcL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Absolute neutrophil count >= 1,500/mcL",
            "criterions": [
                {
                    "exact_snippets": "Absolute neutrophil count >= 1,500/mcL",
                    "criterion": "absolute neutrophil count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1500,
                                "unit": "mcL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Platelets >= 100,000/mcL",
            "criterions": [
                {
                    "exact_snippets": "Platelets >= 100,000/mcL",
                    "criterion": "platelets",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100000,
                                "unit": "mcL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Total bilirubin =< institutional upper limits of normal",
            "criterions": [
                {
                    "exact_snippets": "Total bilirubin =< institutional upper limits of normal",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "institutional upper limits of normal"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal",
            "criterions": [
                {
                    "exact_snippets": "Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) ... =< 2.5 x institutional upper limit of normal",
                    "criterion": "aspartate aminotransferase (AST)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "x institutional upper limit of normal"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ... =< 2.5 x institutional upper limit of normal",
                    "criterion": "alanine aminotransferase (ALT)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "x institutional upper limit of normal"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) =< upper limit of normal (ULN) per institutional laboratory range",
            "criterions": [
                {
                    "exact_snippets": "Partial thromboplastin time (PTT) ... =< upper limit of normal (ULN)",
                    "criterion": "partial thromboplastin time (PTT)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "activated partial thromboplastin time (aPTT) ... =< upper limit of normal (ULN)",
                    "criterion": "activated partial thromboplastin time (aPTT)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* International normalized ratio (INR) =< 1.5",
            "criterions": [
                {
                    "exact_snippets": "International normalized ratio (INR) =< 1.5",
                    "criterion": "International normalized ratio (INR)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "N/A"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Creatinine within normal institutional limits OR creatinine clearance > 40 mL/min per 24 hour (h) urine collection or calculated according to the Cockcroft-Gault formula",
            "criterions": [
                {
                    "exact_snippets": "Creatinine within normal institutional limits",
                    "criterion": "creatinine",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": "within normal institutional limits"
                        }
                    ]
                },
                {
                    "exact_snippets": "creatinine clearance > 40 mL/min per 24 hour (h) urine collection",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "clearance rate",
                            "expected_value": {
                                "operator": ">",
                                "value": 40,
                                "unit": "mL/min"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "creatinine clearance ... calculated according to the Cockcroft-Gault formula",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "calculation method",
                            "expected_value": "Cockcroft-Gault formula"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Generally well-controlled blood pressure with systolic blood pressure =< 140 mmHg AND diastolic blood pressure =< 90 mmHg prior to enrollment; the use of anti-hypertensive medications to control hypertension is permitted",
            "criterions": [
                {
                    "exact_snippets": "Generally well-controlled blood pressure with systolic blood pressure =< 140 mmHg",
                    "criterion": "systolic blood pressure",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<=",
                                "value": 140,
                                "unit": "mmHg"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "diastolic blood pressure =< 90 mmHg",
                    "criterion": "diastolic blood pressure",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<=",
                                "value": 90,
                                "unit": "mmHg"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "the use of anti-hypertensive medications to control hypertension is permitted",
                    "criterion": "use of anti-hypertensive medications",
                    "requirements": [
                        {
                            "requirement_type": "permission",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must have a tumor site amenable to biopsy as determined by the treating investigator; any questions regarding suitability of a site for biopsy will be adjudicated by the principal investigator",
            "criterions": [
                {
                    "exact_snippets": "tumor site amenable to biopsy",
                    "criterion": "tumor site",
                    "requirements": [
                        {
                            "requirement_type": "biopsy suitability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must be willing to consent to tumor biopsy for research purposes",
            "criterions": [
                {
                    "exact_snippets": "Patients must be willing to consent to tumor biopsy",
                    "criterion": "tumor biopsy consent",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients should have archival tumor tissue (either unstained slides or tumor blocks) available for retrieval",
            "criterions": [
                {
                    "exact_snippets": "archival tumor tissue ... available",
                    "criterion": "archival tumor tissue",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* The effects of AMG 386 are known to be detrimental to fetal development; for this reason and because inhibitors of angiogenesis as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential 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, and 6 months after completion of AMG 386; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of AMG 386 and bevacizumab, pazopanib, sunitinib, or sorafenib administration",
            "criterions": [
                {
                    "exact_snippets": "women of child-bearing potential 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, and 6 months after completion of AMG 386",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately",
                    "criterion": "pregnancy status",
                    "requirements": [
                        {
                            "requirement_type": "notification",
                            "expected_value": "inform treating physician immediately"
                        }
                    ]
                },
                {
                    "exact_snippets": "men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of AMG 386 and bevacizumab, pazopanib, sunitinib, or sorafenib administration",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Ability to understand and the willingness to sign a written informed consent document",
            "criterions": [
                {
                    "exact_snippets": "Ability to understand",
                    "criterion": "cognitive ability",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "willingness to sign a written informed consent document",
                    "criterion": "willingness to consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "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": "* Intolerance of prior treatment with bevacizumab, pazopanib, sorafenib, or sunitinib; Note: subjects who required a dose reduction of pazopanib, sorafenib, or sunitinib during prior therapy MAY be eligible if they tolerated the agent after dose level reduction (to a minimum of dose level -2 as defined in this protocol)",
            "criterions": [
                {
                    "exact_snippets": "Intolerance of prior treatment with bevacizumab, pazopanib, sorafenib, or sunitinib",
                    "criterion": "intolerance of prior treatment",
                    "requirements": [
                        {
                            "requirement_type": "medications",
                            "expected_value": [
                                "bevacizumab",
                                "pazopanib",
                                "sorafenib",
                                "sunitinib"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "subjects who required a dose reduction of pazopanib, sorafenib, or sunitinib during prior therapy MAY be eligible if they tolerated the agent after dose level reduction (to a minimum of dose level -2 as defined in this protocol)",
                    "criterion": "dose reduction tolerance",
                    "requirements": [
                        {
                            "requirement_type": "medications",
                            "expected_value": [
                                "pazopanib",
                                "sorafenib",
                                "sunitinib"
                            ]
                        },
                        {
                            "requirement_type": "dose level",
                            "expected_value": {
                                "operator": "<=",
                                "value": -2,
                                "unit": "dose level"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Central nervous system metastases unless: (1) metastases have been treated and have remained controlled for at least two weeks following treatment, AND (2) patient has no residual neurological dysfunction off corticosteroids for at least one week; a CT or MRI to evaluate for central nervous system (CNS) disease is required for symptomatic patients only",
            "criterions": [
                {
                    "exact_snippets": "Central nervous system metastases unless: (1) metastases have been treated and have remained controlled for at least two weeks following treatment",
                    "criterion": "central nervous system metastases",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "treated"
                        },
                        {
                            "requirement_type": "control duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "patient has no residual neurological dysfunction off corticosteroids for at least one week",
                    "criterion": "neurological dysfunction",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "corticosteroid status",
                            "expected_value": "off"
                        },
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "week"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "a CT or MRI to evaluate for central nervous system (CNS) disease is required for symptomatic patients only",
                    "criterion": "CT or MRI evaluation for CNS disease",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": "required for symptomatic patients only"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of venous or arterial thromboembolism within 12 months prior to enrollment/randomization",
            "criterions": [
                {
                    "exact_snippets": "History of venous or arterial thromboembolism within 12 months prior to enrollment/randomization",
                    "criterion": "venous or arterial thromboembolism",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 12,
                                        "unit": "months"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of clinically significant bleeding within 6 months of enrollment/randomization",
            "criterions": [
                {
                    "exact_snippets": "History of clinically significant bleeding within 6 months",
                    "criterion": "clinically significant bleeding",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 6,
                                        "unit": "months"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Currently or previously treated with AMG 386, or other molecules that inhibit the angiopoietins or Tie2 receptor",
            "criterions": [
                {
                    "exact_snippets": "Currently or previously treated with AMG 386",
                    "criterion": "treatment with AMG 386",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": [
                                "current",
                                "previous"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "other molecules that inhibit the angiopoietins or Tie2 receptor",
                    "criterion": "treatment with angiopoietin or Tie2 receptor inhibitors",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": [
                                "current",
                                "previous"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Clinically significant cardiovascular disease within 12 months prior to enrollment/randomization, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication or placement of percutaneous transluminal coronary angioplasty/stent",
            "criterions": [
                {
                    "exact_snippets": "Clinically significant cardiovascular disease within 12 months prior to enrollment/randomization",
                    "criterion": "cardiovascular disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "clinically significant"
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 12 months prior to enrollment/randomization"
                        }
                    ]
                },
                {
                    "exact_snippets": "myocardial infarction",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "unstable angina",
                    "criterion": "unstable angina",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "grade 2 or greater peripheral vascular disease",
                    "criterion": "peripheral vascular disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "cerebrovascular accident",
                    "criterion": "cerebrovascular accident",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "transient ischemic attack",
                    "criterion": "transient ischemic attack",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "congestive heart failure",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "arrhythmias not controlled by outpatient medication",
                    "criterion": "arrhythmias",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": "not controlled by outpatient medication"
                        }
                    ]
                },
                {
                    "exact_snippets": "placement of percutaneous transluminal coronary angioplasty/stent",
                    "criterion": "percutaneous transluminal coronary angioplasty/stent",
                    "requirements": [
                        {
                            "requirement_type": "placement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Major surgery within 28 days prior to enrollment or still recovering from prior surgery",
            "criterions": [
                {
                    "exact_snippets": "Major surgery within 28 days prior to enrollment",
                    "criterion": "major surgery",
                    "requirements": [
                        {
                            "requirement_type": "time since surgery",
                            "expected_value": {
                                "operator": "<",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "still recovering from prior surgery",
                    "criterion": "recovery from prior surgery",
                    "requirements": [
                        {
                            "requirement_type": "recovery status",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Minor surgical procedures except placement of tunneled central venous access device within 3 days prior to enrollment",
            "criterions": [
                {
                    "exact_snippets": "Minor surgical procedures except placement of tunneled central venous access device within 3 days prior to enrollment",
                    "criterion": "minor surgical procedures",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 3,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "placement of tunneled central venous access device within 3 days prior to enrollment",
                    "criterion": "placement of tunneled central venous access device",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 3,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Non-healing wound, ulcer (including gastrointestinal), or fracture",
            "criterions": [
                {
                    "exact_snippets": "Non-healing wound",
                    "criterion": "wound",
                    "requirements": [
                        {
                            "requirement_type": "healing status",
                            "expected_value": "non-healing"
                        }
                    ]
                },
                {
                    "exact_snippets": "ulcer (including gastrointestinal)",
                    "criterion": "ulcer",
                    "requirements": [
                        {
                            "requirement_type": "healing status",
                            "expected_value": "non-healing"
                        }
                    ]
                },
                {
                    "exact_snippets": "fracture",
                    "criterion": "fracture",
                    "requirements": [
                        {
                            "requirement_type": "healing status",
                            "expected_value": "non-healing"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Subject not consenting to the use of highly effective contraceptive precautions (e.g., double barrier method [i.e., condom plus diaphragm]) during the course of the study and for 6 months after administration of the last study medication",
            "criterions": [
                {
                    "exact_snippets": "Subject not consenting to the use of highly effective contraceptive precautions",
                    "criterion": "use of highly effective contraceptive precautions",
                    "requirements": [
                        {
                            "requirement_type": "consent",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "(e.g., double barrier method [i.e., condom plus diaphragm])",
                    "criterion": "contraceptive method",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "double barrier method",
                                "condom plus diaphragm"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "during the course of the study and for 6 months after administration of the last study medication",
                    "criterion": "duration of contraceptive use",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "during the course of the study and for 6 months after administration of the last study medication"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of allergic reactions attributed to compounds of similar chemical or biologic composition to AMG 386 or the anti-VEGF agent used in study",
            "criterions": [
                {
                    "exact_snippets": "History of allergic reactions attributed to compounds of similar chemical or biologic composition to AMG 386",
                    "criterion": "allergic reactions to compounds similar to AMG 386",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "History of allergic reactions attributed to compounds of similar chemical or biologic composition to ... the anti-VEGF agent used in study",
                    "criterion": "allergic reactions to compounds similar to anti-VEGF agent",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of allergic reactions to bacterially-produced proteins",
            "criterions": [
                {
                    "exact_snippets": "History of allergic reactions to bacterially-produced proteins",
                    "criterion": "allergic reactions to bacterially-produced proteins",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who have not yet completed at least 21 days (30 days for prior monoclonal antibody therapy) since ending other investigational device or drug trials, or who are currently receiving other investigational treatments",
            "criterions": [
                {
                    "exact_snippets": "Patients who have not yet completed at least 21 days ... since ending other investigational device or drug trials",
                    "criterion": "time since ending other investigational device or drug trials",
                    "requirements": [
                        {
                            "requirement_type": "time elapsed",
                            "expected_value": {
                                "operator": ">=",
                                "value": 21,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "30 days for prior monoclonal antibody therapy",
                    "criterion": "time since ending prior monoclonal antibody therapy",
                    "requirements": [
                        {
                            "requirement_type": "time elapsed",
                            "expected_value": {
                                "operator": ">=",
                                "value": 30,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "currently receiving other investigational treatments",
                    "criterion": "current investigational treatments",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients receiving any medications or substances that are strong inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP450 3A4) are ineligible; caution is advised for patients requiring weak or moderate CYP450 3A4 inhibitors or inducers; specifically prohibited medicines include indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, nefazodone, carbamazepine, phenobarbital, phenytoin, pioglitazone, rifabutin, rifampin, St. John's wort, and troglitazone",
            "criterions": [
                {
                    "exact_snippets": "Patients receiving any medications or substances that are strong inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP450 3A4) are ineligible",
                    "criterion": "medications or substances affecting CYP450 3A4",
                    "requirements": [
                        {
                            "requirement_type": "strength",
                            "expected_value": "strong inhibitors or inducers"
                        }
                    ]
                },
                {
                    "exact_snippets": "caution is advised for patients requiring weak or moderate CYP450 3A4 inhibitors or inducers",
                    "criterion": "medications or substances affecting CYP450 3A4",
                    "requirements": [
                        {
                            "requirement_type": "strength",
                            "expected_value": "weak or moderate inhibitors or inducers"
                        }
                    ]
                },
                {
                    "exact_snippets": "specifically prohibited medicines include indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, nefazodone, carbamazepine, phenobarbital, phenytoin, pioglitazone, rifabutin, rifampin, St. John's wort, and troglitazone",
                    "criterion": "prohibited medicines",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "indinavir",
                                "nelfinavir",
                                "ritonavir",
                                "clarithromycin",
                                "itraconazole",
                                "ketoconazole",
                                "nefazodone",
                                "carbamazepine",
                                "phenobarbital",
                                "phenytoin",
                                "pioglitazone",
                                "rifabutin",
                                "rifampin",
                                "St. John's wort",
                                "troglitazone"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection",
                    "criterion": "ongoing or active infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Uncontrolled intercurrent illness including, but not limited to, ... symptomatic congestive heart failure",
                    "criterion": "symptomatic congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Uncontrolled intercurrent illness including, but not limited to, ... unstable angina pectoris",
                    "criterion": "unstable angina pectoris",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Uncontrolled intercurrent illness including, but not limited to, ... cardiac arrhythmia",
                    "criterion": "cardiac arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Uncontrolled intercurrent illness including, but not limited to, ... psychiatric illness/social situations that would limit compliance with study requirements",
                    "criterion": "psychiatric illness/social situations",
                    "requirements": [
                        {
                            "requirement_type": "impact on compliance",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Pregnant women are excluded from this study because AMG 386, bevacizumab, pazopanib, sorafenib, and sunitinib are inhibitors of angiogenesis with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AMG 386, breastfeeding must be discontinued if the mother is treated with AMG 386",
            "criterions": [
                {
                    "exact_snippets": "Pregnant women are excluded",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "breastfeeding must be discontinued if the mother is treated with AMG 386",
                    "criterion": "breastfeeding",
                    "requirements": [
                        {
                            "requirement_type": "discontinuation",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with pazopanib, sorafenib, or sunitinib; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated",
            "criterions": [
                {
                    "exact_snippets": "Human immunodeficiency virus (HIV)-positive patients",
                    "criterion": "HIV status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "patients on combination antiretroviral therapy",
                    "criterion": "combination antiretroviral therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Inability to take oral medications on a continuous basis; patients who are to take pazopanib, sorafenib, or sunitinib and are unable to swallow pills whole are ineligible (the pills cannot be crushed or broken)",
            "criterions": [
                {
                    "exact_snippets": "Inability to take oral medications on a continuous basis",
                    "criterion": "ability to take oral medications",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "patients who are to take pazopanib, sorafenib, or sunitinib and are unable to swallow pills whole are ineligible",
                    "criterion": "ability to swallow pills whole",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "the pills cannot be crushed or broken",
                    "criterion": "pills",
                    "requirements": [
                        {
                            "requirement_type": "modification",
                            "expected_value": "cannot be crushed or broken"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any condition which in the investigator's opinion makes the subject unsuitable for study participation",
            "criterions": [
                {
                    "exact_snippets": "Any condition which in the investigator's opinion makes the subject unsuitable for study participation",
                    "criterion": "suitability for study participation",
                    "requirements": [
                        {
                            "requirement_type": "opinion",
                            "expected_value": "investigator's opinion"
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [
        {
            "line": "* Urinary protein =< 100 mg/dL in urinalysis or =< 1+ on dipstick, unless quantitative protein is < 1000 mg in a 24 h urine sample",
            "criterions": [
                {
                    "exact_snippets": "Urinary protein =< 100 mg/dL in urinalysis",
                    "criterion": "urinary protein level in urinalysis",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 100,
                                "unit": "mg/dL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "urinary protein ... =< 1+ on dipstick",
                    "criterion": "urinary protein level on dipstick",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "+"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "quantitative protein ... < 1000 mg in a 24 h urine sample",
                    "criterion": "quantitative protein in 24 h urine sample",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<",
                                "value": 1000,
                                "unit": "mg"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "failed_exclusion": [
        {
            "line": "* Unresolved toxicities from prior systemic therapy that are Common Terminology Criteria in Adverse Events (CTCAE) version 3.0 or 4.0 >= grade 2 in severity except alopecia",
            "criterions": [
                {
                    "exact_snippets": "Unresolved toxicities from prior systemic therapy ... CTCAE version 3.0 or 4.0 >= grade 2 in severity",
                    "criterion": "unresolved toxicities from prior systemic therapy",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "except alopecia",
                    "criterion": "alopecia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who have had anti-VEGFR tyrosine kinase inhibitor within 1 week, mTOR inhibitor within 1 week or anti-VEGF antibody therapy within 3 weeks prior to entering the study; patients who have had other forms of chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier",
            "criterions": [
                {
                    "exact_snippets": "anti-VEGFR tyrosine kinase inhibitor within 1 week",
                    "criterion": "anti-VEGFR tyrosine kinase inhibitor",
                    "requirements": [
                        {
                            "requirement_type": "time since last administration",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "week"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "mTOR inhibitor within 1 week",
                    "criterion": "mTOR inhibitor",
                    "requirements": [
                        {
                            "requirement_type": "time since last administration",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "week"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "anti-VEGF antibody therapy within 3 weeks",
                    "criterion": "anti-VEGF antibody therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last administration",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "other forms of chemotherapy or radiotherapy within 4 weeks",
                    "criterion": "other forms of chemotherapy or radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last administration",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "nitrosoureas or mitomycin C ... within 6 weeks",
                    "criterion": "nitrosoureas or mitomycin C",
                    "requirements": [
                        {
                            "requirement_type": "time since last administration",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "not recovered from adverse events due to agents administered more than 4 weeks earlier",
                    "criterion": "recovery from adverse events",
                    "requirements": [
                        {
                            "requirement_type": "recovery status",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "failed_miscellaneous": []
}