{
    "info": {
        "nct_id": "NCT01349660",
        "official_title": "Phase I/II Study of the Combination of BKM120 and Bevacizumab in Patients With Refractory Solid Tumors (Phase I) and Relapsed/Refractory Glioblastoma Multiforme (Phase II)",
        "inclusion_criteria": "Phase I ONLY:\n\n* Advanced, metastatic solid tumor that has progressed after standard therapy, or is a tumor type resistant to therapy, and for which bevacizumab is clinically appropriate.\n* Patient may have measurable disease or non-measureable disease as defined by RECIST v1.1 criteria\n\nPhase II ONLY:\n\n* Progressive GBM after treatment with surgical resection (if possible) and 1st line radiation/chemotherapy.\n* No previous treatment with a PI3K inhibitor. Previous treatment with bevacizumab as a component of first-line therapy is allowed.\n* At least one measurable or evaluable lesion definable by MRI scan. Disease must be measurable by RANO criteria.\n* Archival tumor tissue available for correlative testing.\n\nALL PATIENTS:\n\n* Patient must be ≥ 4 weeks from administration of last dose of cancer therapy (including radiation therapy, biologic therapy, hormonal therapy, or chemotherapy). Patients who receive a small molecule targeted therapy as part of their first line treatment regimen must be ≥ 4 weeks or ≥ 5 half lives from administration of last dose, whichever is shorter. The patient must have recovered from or come to a new chronic or stable baseline from all treatment-related toxicities.\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.\n* Life expectancy of ≥ 3 months.\n* Adequate hematologic, hepatic, and renal function.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Patients with diarrhea ≥ grade 2.\n* Patients with uncontrolled type I or type II diabetes mellitus, defined as a fasting plasma glucose ≥120 mg/dL.\n* Patients who have received prior treatment with a P13K inhibitor.\n* Treatment with therapeutic doses of coumarin-type anticoagulants (maximum daily dose of 1 mg allowed for port line patency permitted).\n* Patient has active cardiac disease including any of the following:\n\n  * Left ventricular ejection fraction (LVEF) < 50% as determined by Multiple Grated acquisition (MUGA) scan or echocardiogram (ECHO)\n  * QTc > 480 msec on screening ECG (using the QTcF formula)\n  * Angina pectoris that requires the use of anti-anginal medication\n  * Ventricular arrhythmias except for benign premature ventricular contractions\n  * Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication\n  * Conduction abnormality requiring a pacemaker\n  * Valvular disease with documented compromise in cardiac function\n  * Symptomatic pericarditis\n* Patients who are currently receiving treatment with medication with a known risk to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug.\n* Patients with clinical history of hemoptysis or hematemesis (defined as having bright red blood of ½ teaspoon or more per episode) ≤1 month prior to study enrollment.\n* Patients with any history of a bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation)\n* Patients who have received chemotherapy or targeted anticancer therapy ≤ 4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug must recover to a grade 1 before starting the trial.\n* Patients who have received any continuous or intermittent small molecule therapeutics (excluding monoclonal antibodies) ≤ 5 effective half lives prior to starting study drug or who have not recovered from side effects of such therapy.\n* Patients who have been treated with any hematopoietic colony-stimulating factors (e.g. G-CSF, GM-CSF) ≤ 2 weeks prior to starting study drug. Erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment may be continued.\n* Major surgical procedure, open biopsy, intracranial biopsy, ventriculoperitoneal shunt or significant traumatic injury ≤ 28 days prior to entry.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "Phase I ONLY:",
            "criterions": [
                {
                    "exact_snippets": "Phase I ONLY",
                    "criterion": "trial phase",
                    "requirements": [
                        {
                            "requirement_type": "specificity",
                            "expected_value": "Phase I"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Advanced, metastatic solid tumor that has progressed after standard therapy, or is a tumor type resistant to therapy, and for which bevacizumab is clinically appropriate.",
            "criterions": [
                {
                    "exact_snippets": "Advanced, metastatic solid tumor",
                    "criterion": "solid tumor",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "advanced"
                        },
                        {
                            "requirement_type": "metastasis",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "tumor that has progressed after standard therapy",
                    "criterion": "tumor progression",
                    "requirements": [
                        {
                            "requirement_type": "progression after therapy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "tumor type resistant to therapy",
                    "criterion": "tumor resistance",
                    "requirements": [
                        {
                            "requirement_type": "resistance to therapy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "for which bevacizumab is clinically appropriate",
                    "criterion": "bevacizumab appropriateness",
                    "requirements": [
                        {
                            "requirement_type": "clinical appropriateness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patient may have measurable disease or non-measureable disease as defined by RECIST v1.1 criteria",
            "criterions": [
                {
                    "exact_snippets": "measurable disease",
                    "criterion": "disease measurability",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "non-measureable disease",
                    "criterion": "disease measurability",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Phase II ONLY:",
            "criterions": [
                {
                    "exact_snippets": "Phase II ONLY",
                    "criterion": "trial phase",
                    "requirements": [
                        {
                            "requirement_type": "phase",
                            "expected_value": "II"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Progressive GBM after treatment with surgical resection (if possible) and 1st line radiation/chemotherapy.",
            "criterions": [
                {
                    "exact_snippets": "Progressive GBM",
                    "criterion": "GBM",
                    "requirements": [
                        {
                            "requirement_type": "progression",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "treatment with surgical resection (if possible)",
                    "criterion": "surgical resection",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "treatment with ... 1st line radiation/chemotherapy",
                    "criterion": "1st line radiation/chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* No previous treatment with a PI3K inhibitor. Previous treatment with bevacizumab as a component of first-line therapy is allowed.",
            "criterions": [
                {
                    "exact_snippets": "No previous treatment with a PI3K inhibitor",
                    "criterion": "previous treatment with a PI3K inhibitor",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Previous treatment with bevacizumab as a component of first-line therapy is allowed",
                    "criterion": "previous treatment with bevacizumab as a component of first-line therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* At least one measurable or evaluable lesion definable by MRI scan. Disease must be measurable by RANO criteria.",
            "criterions": [
                {
                    "exact_snippets": "At least one measurable or evaluable lesion",
                    "criterion": "lesion",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "N/A"
                            }
                        },
                        {
                            "requirement_type": "measurability",
                            "expected_value": [
                                "measurable",
                                "evaluable"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "definable by MRI scan",
                    "criterion": "lesion",
                    "requirements": [
                        {
                            "requirement_type": "definability",
                            "expected_value": "MRI scan"
                        }
                    ]
                },
                {
                    "exact_snippets": "Disease must be measurable by RANO criteria",
                    "criterion": "disease",
                    "requirements": [
                        {
                            "requirement_type": "measurability",
                            "expected_value": "RANO criteria"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Archival tumor tissue available for correlative testing.",
            "criterions": [
                {
                    "exact_snippets": "Archival tumor tissue available",
                    "criterion": "archival tumor tissue",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "correlative testing",
                    "criterion": "correlative testing",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patient must be ≥ 4 weeks from administration of last dose of cancer therapy (including radiation therapy, biologic therapy, hormonal therapy, or chemotherapy). Patients who receive a small molecule targeted therapy as part of their first line treatment regimen must be ≥ 4 weeks or ≥ 5 half lives from administration of last dose, whichever is shorter. The patient must have recovered from or come to a new chronic or stable baseline from all treatment-related toxicities.",
            "criterions": [
                {
                    "exact_snippets": "Patient must be ≥ 4 weeks from administration of last dose of cancer therapy",
                    "criterion": "time since last cancer therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last dose",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients who receive a small molecule targeted therapy ... must be ≥ 4 weeks or ≥ 5 half lives from administration of last dose, whichever is shorter",
                    "criterion": "time since last small molecule targeted therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last dose",
                            "expected_value": "≥ 4 weeks or ≥ 5 half lives, whichever is shorter"
                        }
                    ]
                },
                {
                    "exact_snippets": "The patient must have recovered from or come to a new chronic or stable baseline from all treatment-related toxicities",
                    "criterion": "recovery from treatment-related toxicities",
                    "requirements": [
                        {
                            "requirement_type": "recovery status",
                            "expected_value": "recovered or new chronic or stable baseline"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 1,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Life expectancy of ≥ 3 months.",
            "criterions": [
                {
                    "exact_snippets": "Life expectancy of ≥ 3 months.",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate hematologic, hepatic, and renal function.",
            "criterions": [
                {
                    "exact_snippets": "Adequate hematologic ... function.",
                    "criterion": "hematologic function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate ... hepatic ... function.",
                    "criterion": "hepatic function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate ... renal function.",
                    "criterion": "renal function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "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": "* Patients with diarrhea ≥ grade 2.",
            "criterions": [
                {
                    "exact_snippets": "diarrhea ≥ grade 2",
                    "criterion": "diarrhea",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "grade"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with uncontrolled type I or type II diabetes mellitus, defined as a fasting plasma glucose ≥120 mg/dL.",
            "criterions": [
                {
                    "exact_snippets": "uncontrolled type I or type II diabetes mellitus",
                    "criterion": "diabetes mellitus",
                    "requirements": [
                        {
                            "requirement_type": "control status",
                            "expected_value": "uncontrolled"
                        },
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "type I",
                                "type II"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "fasting plasma glucose ≥120 mg/dL",
                    "criterion": "fasting plasma glucose",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 120,
                                "unit": "mg/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who have received prior treatment with a P13K inhibitor.",
            "criterions": [
                {
                    "exact_snippets": "Patients who have received prior treatment with a P13K inhibitor",
                    "criterion": "prior treatment with a P13K inhibitor",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Treatment with therapeutic doses of coumarin-type anticoagulants (maximum daily dose of 1 mg allowed for port line patency permitted).",
            "criterions": [
                {
                    "exact_snippets": "Treatment with therapeutic doses of coumarin-type anticoagulants",
                    "criterion": "coumarin-type anticoagulants",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "maximum daily dose of 1 mg allowed",
                    "criterion": "coumarin-type anticoagulants",
                    "requirements": [
                        {
                            "requirement_type": "maximum daily dose",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "mg"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "port line patency permitted",
                    "criterion": "port line patency",
                    "requirements": [
                        {
                            "requirement_type": "permitted",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patient has active cardiac disease including any of the following:",
            "criterions": [
                {
                    "exact_snippets": "active cardiac disease",
                    "criterion": "cardiac disease",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "active"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Left ventricular ejection fraction (LVEF) < 50% as determined by Multiple Grated acquisition (MUGA) scan or echocardiogram (ECHO)",
            "criterions": [
                {
                    "exact_snippets": "Left ventricular ejection fraction (LVEF) < 50%",
                    "criterion": "left ventricular ejection fraction (LVEF)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<",
                                "value": 50,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* QTc > 480 msec on screening ECG (using the QTcF formula)",
            "criterions": [
                {
                    "exact_snippets": "QTc > 480 msec on screening ECG (using the QTcF formula)",
                    "criterion": "QTc interval",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 480,
                                "unit": "msec"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Angina pectoris that requires the use of anti-anginal medication",
            "criterions": [
                {
                    "exact_snippets": "Angina pectoris that requires the use of anti-anginal medication",
                    "criterion": "angina pectoris",
                    "requirements": [
                        {
                            "requirement_type": "medication requirement",
                            "expected_value": "anti-anginal medication"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Ventricular arrhythmias except for benign premature ventricular contractions",
            "criterions": [
                {
                    "exact_snippets": "Ventricular arrhythmias except for benign premature ventricular contractions",
                    "criterion": "ventricular arrhythmias",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": "benign premature ventricular contractions"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication",
            "criterions": [
                {
                    "exact_snippets": "Supraventricular and nodal arrhythmias",
                    "criterion": "arrhythmias",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "supraventricular",
                                "nodal"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "requiring a pacemaker",
                    "criterion": "pacemaker requirement",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "not controlled with medication",
                    "criterion": "medication control",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Conduction abnormality requiring a pacemaker",
            "criterions": [
                {
                    "exact_snippets": "Conduction abnormality requiring a pacemaker",
                    "criterion": "conduction abnormality",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "requiring a pacemaker"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Valvular disease with documented compromise in cardiac function",
            "criterions": [
                {
                    "exact_snippets": "Valvular disease",
                    "criterion": "valvular disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "documented compromise in cardiac function",
                    "criterion": "cardiac function",
                    "requirements": [
                        {
                            "requirement_type": "compromise",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Symptomatic pericarditis",
            "criterions": [
                {
                    "exact_snippets": "Symptomatic pericarditis",
                    "criterion": "pericarditis",
                    "requirements": [
                        {
                            "requirement_type": "symptomatic",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who are currently receiving treatment with medication with a known risk to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug.",
            "criterions": [
                {
                    "exact_snippets": "currently receiving treatment with medication with a known risk to prolong the QT interval",
                    "criterion": "medication with risk to prolong QT interval",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "currently receiving treatment with medication ... inducing Torsades de Pointes",
                    "criterion": "medication inducing Torsades de Pointes",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "treatment cannot either be discontinued or switched to a different medication",
                    "criterion": "ability to discontinue or switch medication",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with clinical history of hemoptysis or hematemesis (defined as having bright red blood of ½ teaspoon or more per episode) ≤1 month prior to study enrollment.",
            "criterions": [
                {
                    "exact_snippets": "clinical history of hemoptysis",
                    "criterion": "hemoptysis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "clinical history of ... hematemesis",
                    "criterion": "hematemesis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "bright red blood of ½ teaspoon or more per episode",
                    "criterion": "amount of blood per episode",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 0.5,
                                "unit": "teaspoon"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "≤1 month prior to study enrollment",
                    "criterion": "time since last episode",
                    "requirements": [
                        {
                            "requirement_type": "time",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "month"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with any history of a bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation)",
            "criterions": [
                {
                    "exact_snippets": "any history of a bleeding diathesis",
                    "criterion": "bleeding diathesis",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "any history of ... coagulopathy",
                    "criterion": "coagulopathy",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "absence of therapeutic anticoagulation",
                    "criterion": "therapeutic anticoagulation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who have received any continuous or intermittent small molecule therapeutics (excluding monoclonal antibodies) ≤ 5 effective half lives prior to starting study drug or who have not recovered from side effects of such therapy.",
            "criterions": [
                {
                    "exact_snippets": "Patients who have received any continuous or intermittent small molecule therapeutics (excluding monoclonal antibodies) ≤ 5 effective half lives prior to starting study drug",
                    "criterion": "prior small molecule therapeutics",
                    "requirements": [
                        {
                            "requirement_type": "time since last dose",
                            "expected_value": {
                                "operator": "<=",
                                "value": 5,
                                "unit": "effective half lives"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients ... who have not recovered from side effects of such therapy",
                    "criterion": "recovery from side effects",
                    "requirements": [
                        {
                            "requirement_type": "recovery status",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who have been treated with any hematopoietic colony-stimulating factors (e.g. G-CSF, GM-CSF) ≤ 2 weeks prior to starting study drug. Erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment may be continued.",
            "criterions": [
                {
                    "exact_snippets": "treated with any hematopoietic colony-stimulating factors (e.g. G-CSF, GM-CSF) ≤ 2 weeks prior to starting study drug",
                    "criterion": "treatment with hematopoietic colony-stimulating factors",
                    "requirements": [
                        {
                            "requirement_type": "time since treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment may be continued",
                    "criterion": "Erythropoietin or darbepoetin therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since initiation",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Major surgical procedure, open biopsy, intracranial biopsy, ventriculoperitoneal shunt or significant traumatic injury ≤ 28 days prior to entry.",
            "criterions": [
                {
                    "exact_snippets": "Major surgical procedure ... ≤ 28 days prior to entry.",
                    "criterion": "major surgical procedure",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<=",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "open biopsy ... ≤ 28 days prior to entry.",
                    "criterion": "open biopsy",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<=",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "intracranial biopsy ... ≤ 28 days prior to entry.",
                    "criterion": "intracranial biopsy",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<=",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "ventriculoperitoneal shunt ... ≤ 28 days prior to entry.",
                    "criterion": "ventriculoperitoneal shunt",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<=",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "significant traumatic injury ≤ 28 days prior to entry.",
                    "criterion": "significant traumatic injury",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<=",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [
        {
            "line": "ALL PATIENTS:",
            "criterions": []
        }
    ],
    "failed_exclusion": [
        {
            "line": "* Patients who have received chemotherapy or targeted anticancer therapy ≤ 4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug must recover to a grade 1 before starting the trial.",
            "criterions": [
                {
                    "exact_snippets": "Patients who have received chemotherapy or targeted anticancer therapy ≤ 4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug",
                    "criterion": "prior chemotherapy or targeted anticancer therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients who have received ... nitrosourea, antibodies or mitomycin-C ... ≤ 6 weeks prior to starting study drug",
                    "criterion": "prior nitrosourea, antibodies or mitomycin-C treatment",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 6,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "must recover to a grade 1 before starting the trial",
                    "criterion": "recovery to grade 1",
                    "requirements": [
                        {
                            "requirement_type": "recovery status",
                            "expected_value": "grade 1"
                        }
                    ]
                }
            ]
        }
    ],
    "failed_miscellaneous": []
}