{
    "info": {
        "nct_id": "NCT00042991",
        "official_title": "Phase I/II Trial of Gefitinib and Radiation in Pediatric Patients Newly Diagnosed With Brain Stem Tumors or Incompletely Resected Supratentorial Malignant Gliomas With Phase II Limited to Brain Stem Tumors",
        "inclusion_criteria": "* Tumor:\n\n  * Phase I: newly diagnosed non-disseminated diffuse intrinsic brainstem tumor or newly diagnosed (diagnostic scan must be within 4 weeks prior to treatment initiation), incompletely resected supratentorial malignant glioma (anaplastic astrocytoma, glioblastoma multiforme or other high-grade glioma) (STMG); the STMG group must have residual tumor evident on postoperative MRI or CT\n  * Phase II: only newly diagnosed non-disseminated diffuse intrinsic brain stem glioma patients are eligible\n* Performance status: Karnofsky or Lansky >= 50% assessed within two weeks prior to registration\n* Prior/concurrent therapy:\n\n  * Chemotherapy: no prior therapy allowed, including prior gefitinib treatment\n  * Radiation therapy (XRT): no prior therapy allowed\n  * Bone marrow transplant: none prior\n  * Anti-convulsants: patients with brain stem glioma (BSG) receiving EIACD will not be eligible; patients with STMG will be eligible for this study even if they are receiving enzyme inducting anti-convulsant drugs (EIACD) and will be stratified by use of EIACDs\n  * Growth factors: off all colony forming growth factor(s) > 2 weeks prior to registration (G-CSF, GM-CSF, erythropoietin)\n* ANC > 1,000/ul\n* Platelets > 100,000/ul (transfusion independent)\n* Hemoglobin > 8g/dl (may be transfused)\n* Patients may have bone marrow involvement by disease\n* Creatinine < 2 x normal for age or GFR > 70 ml/min/1.73m^2\n* Bilirubin < 1.5 x normal institutional normal for age\n* SGPT (ALT) < 3 x institutional normal for age\n* Pregnant and/or lactating patients are excluded; patients of childbearing potential should not become pregnant and should not father a child during treatment with gefitinib; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method\n* Signed informed consent according to institutional guidelines must be obtained prior to study entry\nHealthy volunteers allowed\nMust have minimum age of 3 Years\nMust have maximum age of 21 Years",
        "exclusion_criteria": "* Patients with evidence of intramural hemorrhage on a scan obtained prior to enrollment or after enrollment, before treatment\n* Patients with BSG must not be taking enzyme-inducing anticonvulsant drugs\n* Patient must not be receiving any other anticancer or experimental drug therapy\n* Patient must have no uncontrolled infection\n* Patients with significant cardiac, hepatic, gastrointestinal, renal, pulmonary, or psychiatric disease are ineligible; patients with deep venous or arterial thrombosis within 6 weeks of study entry are ineligible\n* Patients with disseminated disease are not permitted\n* Patients with spinal disease requiring craniospinal radiation are not eligible\n* Patients with completely resected supratentorial malignant gliomas patients are ineligible",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Tumor:",
            "criterions": [
                {
                    "exact_snippets": "Tumor",
                    "criterion": "tumor",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Phase I: newly diagnosed non-disseminated diffuse intrinsic brainstem tumor or newly diagnosed (diagnostic scan must be within 4 weeks prior to treatment initiation), incompletely resected supratentorial malignant glioma (anaplastic astrocytoma, glioblastoma multiforme or other high-grade glioma) (STMG); the STMG group must have residual tumor evident on postoperative MRI or CT",
            "criterions": [
                {
                    "exact_snippets": "newly diagnosed non-disseminated diffuse intrinsic brainstem tumor",
                    "criterion": "diffuse intrinsic brainstem tumor",
                    "requirements": [
                        {
                            "requirement_type": "diagnosis status",
                            "expected_value": "newly diagnosed"
                        },
                        {
                            "requirement_type": "dissemination",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "newly diagnosed ... incompletely resected supratentorial malignant glioma (anaplastic astrocytoma, glioblastoma multiforme or other high-grade glioma)",
                    "criterion": "supratentorial malignant glioma",
                    "requirements": [
                        {
                            "requirement_type": "diagnosis status",
                            "expected_value": "newly diagnosed"
                        },
                        {
                            "requirement_type": "resection completeness",
                            "expected_value": "incompletely resected"
                        }
                    ]
                },
                {
                    "exact_snippets": "diagnostic scan must be within 4 weeks prior to treatment initiation",
                    "criterion": "diagnostic scan timing",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "STMG group must have residual tumor evident on postoperative MRI or CT",
                    "criterion": "residual tumor",
                    "requirements": [
                        {
                            "requirement_type": "evidence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Phase II: only newly diagnosed non-disseminated diffuse intrinsic brain stem glioma patients are eligible",
            "criterions": [
                {
                    "exact_snippets": "newly diagnosed",
                    "criterion": "diagnosis status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "newly diagnosed"
                        }
                    ]
                },
                {
                    "exact_snippets": "non-disseminated",
                    "criterion": "disease dissemination",
                    "requirements": [
                        {
                            "requirement_type": "dissemination",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "diffuse intrinsic brain stem glioma",
                    "criterion": "cancer type",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": "diffuse intrinsic brain stem glioma"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Performance status: Karnofsky or Lansky >= 50% assessed within two weeks prior to registration",
            "criterions": [
                {
                    "exact_snippets": "Performance status: Karnofsky or Lansky >= 50%",
                    "criterion": "performance status",
                    "requirements": [
                        {
                            "requirement_type": "scale",
                            "expected_value": [
                                "Karnofsky",
                                "Lansky"
                            ]
                        },
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 50,
                                "unit": "%"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "assessed within two weeks prior to registration",
                    "criterion": "assessment timing",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within two weeks prior to registration"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prior/concurrent therapy:",
            "criterions": [
                {
                    "exact_snippets": "Prior/concurrent therapy",
                    "criterion": "therapy",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": [
                                "prior",
                                "concurrent"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Chemotherapy: no prior therapy allowed, including prior gefitinib treatment",
            "criterions": [
                {
                    "exact_snippets": "Chemotherapy: no prior therapy allowed",
                    "criterion": "prior chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "including prior gefitinib treatment",
                    "criterion": "prior gefitinib treatment",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Radiation therapy (XRT): no prior therapy allowed",
            "criterions": [
                {
                    "exact_snippets": "Radiation therapy (XRT): no prior therapy allowed",
                    "criterion": "prior radiation therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Bone marrow transplant: none prior",
            "criterions": [
                {
                    "exact_snippets": "Bone marrow transplant: none prior",
                    "criterion": "bone marrow transplant",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Anti-convulsants: patients with brain stem glioma (BSG) receiving EIACD will not be eligible; patients with STMG will be eligible for this study even if they are receiving enzyme inducting anti-convulsant drugs (EIACD) and will be stratified by use of EIACDs",
            "criterions": [
                {
                    "exact_snippets": "patients with brain stem glioma (BSG) receiving EIACD will not be eligible",
                    "criterion": "brain stem glioma (BSG)",
                    "requirements": [
                        {
                            "requirement_type": "use of EIACD",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "patients with STMG will be eligible for this study even if they are receiving enzyme inducting anti-convulsant drugs (EIACD)",
                    "criterion": "STMG",
                    "requirements": [
                        {
                            "requirement_type": "use of EIACD",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Growth factors: off all colony forming growth factor(s) > 2 weeks prior to registration (G-CSF, GM-CSF, erythropoietin)",
            "criterions": [
                {
                    "exact_snippets": "Growth factors: off all colony forming growth factor(s) > 2 weeks prior to registration (G-CSF, GM-CSF, erythropoietin)",
                    "criterion": "colony forming growth factors",
                    "requirements": [
                        {
                            "requirement_type": "cessation period",
                            "expected_value": {
                                "operator": ">",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* ANC > 1,000/ul",
            "criterions": [
                {
                    "exact_snippets": "ANC > 1,000/ul",
                    "criterion": "ANC",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">",
                                "value": 1000,
                                "unit": "ul"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Platelets > 100,000/ul (transfusion independent)",
            "criterions": [
                {
                    "exact_snippets": "Platelets > 100,000/ul",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">",
                                "value": 100000,
                                "unit": "ul"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "transfusion independent",
                    "criterion": "transfusion independence",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Hemoglobin > 8g/dl (may be transfused)",
            "criterions": [
                {
                    "exact_snippets": "Hemoglobin > 8g/dl",
                    "criterion": "hemoglobin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">",
                                "value": 8,
                                "unit": "g/dl"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients may have bone marrow involvement by disease",
            "criterions": [
                {
                    "exact_snippets": "bone marrow involvement by disease",
                    "criterion": "bone marrow involvement",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Creatinine < 2 x normal for age or GFR > 70 ml/min/1.73m^2",
            "criterions": [
                {
                    "exact_snippets": "Creatinine < 2 x normal for age",
                    "criterion": "creatinine level",
                    "requirements": [
                        {
                            "requirement_type": "comparison",
                            "expected_value": {
                                "operator": "<",
                                "value": 2,
                                "unit": "x normal for age"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "GFR > 70 ml/min/1.73m^2",
                    "criterion": "glomerular filtration rate (GFR)",
                    "requirements": [
                        {
                            "requirement_type": "comparison",
                            "expected_value": {
                                "operator": ">",
                                "value": 70,
                                "unit": "ml/min/1.73m^2"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Bilirubin < 1.5 x normal institutional normal for age",
            "criterions": [
                {
                    "exact_snippets": "Bilirubin < 1.5 x normal institutional normal for age",
                    "criterion": "bilirubin level",
                    "requirements": [
                        {
                            "requirement_type": "comparison",
                            "expected_value": {
                                "operator": "<",
                                "value": 1.5,
                                "unit": "x normal institutional normal for age"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* SGPT (ALT) < 3 x institutional normal for age",
            "criterions": [
                {
                    "exact_snippets": "SGPT (ALT) < 3 x institutional normal for age",
                    "criterion": "SGPT (ALT)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 3,
                                "unit": "x institutional normal for age"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Pregnant and/or lactating patients are excluded; patients of childbearing potential should not become pregnant and should not father a child during treatment with gefitinib; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method",
            "criterions": [
                {
                    "exact_snippets": "Pregnant and/or lactating patients are excluded",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Pregnant and/or lactating patients are excluded",
                    "criterion": "lactation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "patients of childbearing potential should not become pregnant",
                    "criterion": "childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "pregnancy during treatment",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "patients of childbearing potential should not ... father a child during treatment with gefitinib",
                    "criterion": "childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "fathering a child during treatment",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "pregnancy tests must be obtained in girls who are post-menarchal",
                    "criterion": "post-menarchal girls",
                    "requirements": [
                        {
                            "requirement_type": "pregnancy test",
                            "expected_value": "must be obtained"
                        }
                    ]
                },
                {
                    "exact_snippets": "males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method",
                    "criterion": "reproductive potential",
                    "requirements": [
                        {
                            "requirement_type": "contraceptive method",
                            "expected_value": "agreed to use"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Signed informed consent according to institutional guidelines must be obtained prior to study entry",
            "criterions": [
                {
                    "exact_snippets": "Signed informed consent according to institutional guidelines must be obtained",
                    "criterion": "informed 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 3 Years",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 3 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have maximum age of 21 Years",
            "criterions": [
                {
                    "exact_snippets": "maximum age of 21 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "maximum",
                            "expected_value": {
                                "operator": "<=",
                                "value": 21,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "* Patients with evidence of intramural hemorrhage on a scan obtained prior to enrollment or after enrollment, before treatment",
            "criterions": [
                {
                    "exact_snippets": "evidence of intramural hemorrhage on a scan",
                    "criterion": "intramural hemorrhage",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with BSG must not be taking enzyme-inducing anticonvulsant drugs",
            "criterions": [
                {
                    "exact_snippets": "Patients with BSG",
                    "criterion": "BSG",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "must not be taking enzyme-inducing anticonvulsant drugs",
                    "criterion": "enzyme-inducing anticonvulsant drugs",
                    "requirements": [
                        {
                            "requirement_type": "usage",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patient must not be receiving any other anticancer or experimental drug therapy",
            "criterions": [
                {
                    "exact_snippets": "Patient must not be receiving any other anticancer ... drug therapy",
                    "criterion": "anticancer drug therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Patient must not be receiving any other ... experimental drug therapy",
                    "criterion": "experimental drug therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patient must have no uncontrolled infection",
            "criterions": [
                {
                    "exact_snippets": "no uncontrolled infection",
                    "criterion": "infection",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with disseminated disease are not permitted",
            "criterions": [
                {
                    "exact_snippets": "disseminated disease are not permitted",
                    "criterion": "disseminated disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with spinal disease requiring craniospinal radiation are not eligible",
            "criterions": [
                {
                    "exact_snippets": "spinal disease requiring craniospinal radiation",
                    "criterion": "spinal disease",
                    "requirements": [
                        {
                            "requirement_type": "treatment requirement",
                            "expected_value": "craniospinal radiation"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with completely resected supratentorial malignant gliomas patients are ineligible",
            "criterions": [
                {
                    "exact_snippets": "completely resected supratentorial malignant gliomas",
                    "criterion": "supratentorial malignant gliomas",
                    "requirements": [
                        {
                            "requirement_type": "resection status",
                            "expected_value": "completely resected"
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [
        {
            "line": "* Patients with significant cardiac, hepatic, gastrointestinal, renal, pulmonary, or psychiatric disease are ineligible; patients with deep venous or arterial thrombosis within 6 weeks of study entry are ineligible",
            "criterions": [
                {
                    "exact_snippets": "significant cardiac ... disease are ineligible",
                    "criterion": "cardiac disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "significant hepatic ... disease are ineligible",
                    "criterion": "hepatic disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "significant gastrointestinal ... disease are ineligible",
                    "criterion": "gastrointestinal disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "significant renal ... disease are ineligible",
                    "criterion": "renal disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "significant pulmonary ... disease are ineligible",
                    "criterion": "pulmonary disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "significant psychiatric ... disease are ineligible",
                    "criterion": "psychiatric disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "deep venous or arterial thrombosis within 6 weeks of study entry are ineligible",
                    "criterion": "deep venous or arterial thrombosis",
                    "requirements": [
                        {
                            "requirement_type": "time since occurrence",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "failed_miscellaneous": []
}