{
    "info": {
        "nct_id": "NCT00879073",
        "official_title": "Phase I Study of Bendamustine With Concurrent Whole Brain Radiation Therapy in Patients With Brain Metastases From Solid Tumors",
        "inclusion_criteria": "* Pathologically (histologically or cytologically) proven diagnosis of solid tumor malignancy within 5 years of registration. Pathological confirmation by pathologists at Moffitt Cancer Center is required.\n* Cerebral metastases from known solid tumors diagnosed by contrast-enhanced brain magnetic resonance imaging (MRI) or contrast-enhanced head computed tomography (CT) for patients unable to receive MRIs\n* Single metastases that have been resected\n* Patient may have had prior radiosurgery or surgical resection for brain metastasis. Patients should have completed prior therapy at least 14 days but no longer than 56 days prior to study entry.\n* Karnofsky Performance Status ≥ 70 within 28 days prior to study entry.\n* Expected life span of ≥ 3 months\n* Able to tolerate 3 week course of whole brain radiation therapy\n* Able to receive a lumbar puncture (for post-MTD patients only)\n* Adequate bone marrow, liver and renal function as assessed by the following: Hemoglobin > 9.0 g/dl; Absolute neutrophil count (ANC) > 1,500/mm³; Platelet count > 100,000/mm³; Total bilirubin < 1.5 x upper limit of normal (ULN); Alanine transaminase/Aspartic transaminase (ALT/AST) < 2.5 x the ULN (< 5 x ULN for patients with liver involvement); International normalized ratio (INR) < 1.5 or a prothrombin time/partial thromboplastin time (PT/PTT) within normal limits; Creatinine < 1.5 x ULN\n* Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment.\n* Ability to understand and sign a study-specific written informed consent prior to study entry.\n* Patients receiving systemic therapy are eligible for this study if given >14 days prior to study entry and given no sooner than >14 days post radiation therapy (RT) completion.\n* Complete history and general physical examination within 28 days prior to study entry\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Known hypersensitivity to bendamustine or mannitol\n* Patients with cerebral metastases from unknown primary tumors\n* Patients with cerebral metastases from leukemias or lymphomas\n* Patients with uncontrolled systemic cancer (i.e. evidence of systemic disease progression < 3 months prior to study entry)\n* Systemic chemotherapy ≤14 days prior to study entry or ≤14 days after completing radiotherapy\n* Patients who received prior BCNU wafer (Gliadel®) implantation for surgically resected cerebral metastatic lesions\n* Patients with a life expectancy of less than 3 months\n* Patients who received prior whole brain radiation therapy. As noted above, patients who received prior radiosurgery are allowed\n* Patients with significant hydrocephalous\n* Active clinically serious infection > Common Terminology Criteria for Adverse Events (CTCAE) Grade 2\n* Pregnant or lactating women",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Pathologically (histologically or cytologically) proven diagnosis of solid tumor malignancy within 5 years of registration. Pathological confirmation by pathologists at Moffitt Cancer Center is required.",
            "criterions": [
                {
                    "exact_snippets": "Pathologically (histologically or cytologically) proven diagnosis of solid tumor malignancy",
                    "criterion": "solid tumor malignancy",
                    "requirements": [
                        {
                            "requirement_type": "diagnosis",
                            "expected_value": "pathologically proven"
                        }
                    ]
                },
                {
                    "exact_snippets": "within 5 years of registration",
                    "criterion": "diagnosis timing",
                    "requirements": [
                        {
                            "requirement_type": "time since diagnosis",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 5,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Pathological confirmation by pathologists at Moffitt Cancer Center is required",
                    "criterion": "pathological confirmation",
                    "requirements": [
                        {
                            "requirement_type": "confirmation location",
                            "expected_value": "Moffitt Cancer Center"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Cerebral metastases from known solid tumors diagnosed by contrast-enhanced brain magnetic resonance imaging (MRI) or contrast-enhanced head computed tomography (CT) for patients unable to receive MRIs",
            "criterions": [
                {
                    "exact_snippets": "Cerebral metastases from known solid tumors",
                    "criterion": "cerebral metastases",
                    "requirements": [
                        {
                            "requirement_type": "origin",
                            "expected_value": "known solid tumors"
                        }
                    ]
                },
                {
                    "exact_snippets": "diagnosed by contrast-enhanced brain magnetic resonance imaging (MRI)",
                    "criterion": "diagnosis method",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": "contrast-enhanced brain MRI"
                        }
                    ]
                },
                {
                    "exact_snippets": "diagnosed by ... contrast-enhanced head computed tomography (CT) for patients unable to receive MRIs",
                    "criterion": "diagnosis method",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": "contrast-enhanced head CT"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Single metastases that have been resected",
            "criterions": [
                {
                    "exact_snippets": "Single metastases that have been resected",
                    "criterion": "metastases",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": "single"
                        },
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "resected"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patient may have had prior radiosurgery or surgical resection for brain metastasis. Patients should have completed prior therapy at least 14 days but no longer than 56 days prior to study entry.",
            "criterions": [
                {
                    "exact_snippets": "Patient may have had prior radiosurgery or surgical resection for brain metastasis.",
                    "criterion": "prior treatment for brain metastasis",
                    "requirements": [
                        {
                            "requirement_type": "treatment type",
                            "expected_value": [
                                "radiosurgery",
                                "surgical resection"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients should have completed prior therapy at least 14 days but no longer than 56 days prior to study entry.",
                    "criterion": "completion of prior therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since completion",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 14,
                                        "unit": "days"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 56,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Karnofsky Performance Status ≥ 70 within 28 days prior to study entry.",
            "criterions": [
                {
                    "exact_snippets": "Karnofsky Performance Status ≥ 70",
                    "criterion": "Karnofsky Performance Status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 70,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "within 28 days prior to study entry",
                    "criterion": "timeframe for Karnofsky Performance Status assessment",
                    "requirements": [
                        {
                            "requirement_type": "timeframe",
                            "expected_value": "within 28 days prior to study entry"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Expected life span of ≥ 3 months",
            "criterions": [
                {
                    "exact_snippets": "Expected life span of ≥ 3 months",
                    "criterion": "life span",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Able to tolerate 3 week course of whole brain radiation therapy",
            "criterions": [
                {
                    "exact_snippets": "Able to tolerate 3 week course of whole brain radiation therapy",
                    "criterion": "tolerance to whole brain radiation therapy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": "=",
                                "value": 3,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Able to receive a lumbar puncture (for post-MTD patients only)",
            "criterions": [
                {
                    "exact_snippets": "Able to receive a lumbar puncture",
                    "criterion": "lumbar puncture",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "(for post-MTD patients only)",
                    "criterion": "post-MTD status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate bone marrow, liver and renal function as assessed by the following: Hemoglobin > 9.0 g/dl; Absolute neutrophil count (ANC) > 1,500/mm³; Platelet count > 100,000/mm³; Total bilirubin < 1.5 x upper limit of normal (ULN); Alanine transaminase/Aspartic transaminase (ALT/AST) < 2.5 x the ULN (< 5 x ULN for patients with liver involvement); International normalized ratio (INR) < 1.5 or a prothrombin time/partial thromboplastin time (PT/PTT) within normal limits; Creatinine < 1.5 x ULN",
            "criterions": [
                {
                    "exact_snippets": "Hemoglobin > 9.0 g/dl",
                    "criterion": "hemoglobin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">",
                                "value": 9.0,
                                "unit": "g/dl"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Absolute neutrophil count (ANC) > 1,500/mm³",
                    "criterion": "absolute neutrophil count (ANC)",
                    "requirements": [
                        {
                            "requirement_type": "count",
                            "expected_value": {
                                "operator": ">",
                                "value": 1500,
                                "unit": "mm³"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Platelet count > 100,000/mm³",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "count",
                            "expected_value": {
                                "operator": ">",
                                "value": 100000,
                                "unit": "mm³"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Total bilirubin < 1.5 x upper limit of normal (ULN)",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Alanine transaminase/Aspartic transaminase (ALT/AST) < 2.5 x the ULN (< 5 x ULN for patients with liver involvement)",
                    "criterion": "alanine transaminase/aspartic transaminase (ALT/AST)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 2.5,
                                "unit": "x ULN"
                            }
                        },
                        {
                            "requirement_type": "level for patients with liver involvement",
                            "expected_value": {
                                "operator": "<",
                                "value": 5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "International normalized ratio (INR) < 1.5 or a prothrombin time/partial thromboplastin time (PT/PTT) within normal limits",
                    "criterion": "international normalized ratio (INR)",
                    "requirements": [
                        {
                            "requirement_type": "ratio",
                            "expected_value": {
                                "operator": "<",
                                "value": 1.5,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "prothrombin time/partial thromboplastin time (PT/PTT) within normal limits",
                    "criterion": "prothrombin time/partial thromboplastin time (PT/PTT)",
                    "requirements": [
                        {
                            "requirement_type": "time",
                            "expected_value": "within normal limits"
                        }
                    ]
                },
                {
                    "exact_snippets": "Creatinine < 1.5 x ULN",
                    "criterion": "creatinine level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment.",
            "criterions": [
                {
                    "exact_snippets": "Women of childbearing potential",
                    "criterion": "childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "negative serum pregnancy test",
                    "criterion": "serum pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "performed within 7 days prior to the start of treatment",
                    "criterion": "timing of serum pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "within 7 days prior to the start of treatment"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Ability to understand and sign a study-specific written informed consent prior to study entry.",
            "criterions": [
                {
                    "exact_snippets": "Ability to understand and sign a study-specific written informed consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients receiving systemic therapy are eligible for this study if given >14 days prior to study entry and given no sooner than >14 days post radiation therapy (RT) completion.",
            "criterions": [
                {
                    "exact_snippets": "Patients receiving systemic therapy",
                    "criterion": "systemic therapy",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "given >14 days prior to study entry"
                        }
                    ]
                },
                {
                    "exact_snippets": "systemic therapy ... given no sooner than >14 days post radiation therapy (RT) completion",
                    "criterion": "systemic therapy post RT",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "given no sooner than >14 days post radiation therapy (RT) completion"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Complete history and general physical examination within 28 days prior to study entry",
            "criterions": [
                {
                    "exact_snippets": "Complete history",
                    "criterion": "medical history",
                    "requirements": [
                        {
                            "requirement_type": "completion",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "timeframe",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 28,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "general physical examination",
                    "criterion": "physical examination",
                    "requirements": [
                        {
                            "requirement_type": "completion",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "timeframe",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 28,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "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": "* Known hypersensitivity to bendamustine or mannitol",
            "criterions": [
                {
                    "exact_snippets": "Known hypersensitivity to bendamustine",
                    "criterion": "hypersensitivity to bendamustine",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Known hypersensitivity to ... mannitol",
                    "criterion": "hypersensitivity to mannitol",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with cerebral metastases from unknown primary tumors",
            "criterions": [
                {
                    "exact_snippets": "cerebral metastases",
                    "criterion": "cerebral metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "unknown primary tumors",
                    "criterion": "unknown primary tumors",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with cerebral metastases from leukemias or lymphomas",
            "criterions": [
                {
                    "exact_snippets": "cerebral metastases",
                    "criterion": "cerebral metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "leukemias",
                    "criterion": "leukemias",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "lymphomas",
                    "criterion": "lymphomas",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with uncontrolled systemic cancer (i.e. evidence of systemic disease progression < 3 months prior to study entry)",
            "criterions": [
                {
                    "exact_snippets": "uncontrolled systemic cancer",
                    "criterion": "systemic cancer",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "evidence of systemic disease progression < 3 months prior to study entry",
                    "criterion": "systemic disease progression",
                    "requirements": [
                        {
                            "requirement_type": "time since progression",
                            "expected_value": {
                                "operator": "<",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Systemic chemotherapy ≤14 days prior to study entry or ≤14 days after completing radiotherapy",
            "criterions": [
                {
                    "exact_snippets": "Systemic chemotherapy ≤14 days prior to study entry",
                    "criterion": "systemic chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 14,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Systemic chemotherapy ... ≤14 days after completing radiotherapy",
                    "criterion": "systemic chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since radiotherapy completion",
                            "expected_value": {
                                "operator": "<=",
                                "value": 14,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who received prior BCNU wafer (Gliadel®) implantation for surgically resected cerebral metastatic lesions",
            "criterions": [
                {
                    "exact_snippets": "Patients who received prior BCNU wafer (Gliadel®) implantation",
                    "criterion": "BCNU wafer (Gliadel®) implantation",
                    "requirements": [
                        {
                            "requirement_type": "prior treatment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "surgically resected cerebral metastatic lesions",
                    "criterion": "cerebral metastatic lesions",
                    "requirements": [
                        {
                            "requirement_type": "surgical resection",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with a life expectancy of less than 3 months",
            "criterions": [
                {
                    "exact_snippets": "life expectancy of less than 3 months",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": "<",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who received prior whole brain radiation therapy. As noted above, patients who received prior radiosurgery are allowed",
            "criterions": [
                {
                    "exact_snippets": "Patients who received prior whole brain radiation therapy",
                    "criterion": "prior whole brain radiation therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "patients who received prior radiosurgery are allowed",
                    "criterion": "prior radiosurgery",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with significant hydrocephalous",
            "criterions": [
                {
                    "exact_snippets": "significant hydrocephalous",
                    "criterion": "hydrocephalous",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "significant"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Active clinically serious infection > Common Terminology Criteria for Adverse Events (CTCAE) Grade 2",
            "criterions": [
                {
                    "exact_snippets": "Active clinically serious infection > Common Terminology Criteria for Adverse Events (CTCAE) Grade 2",
                    "criterion": "clinically serious infection",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">",
                                "value": 2,
                                "unit": "CTCAE Grade"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Pregnant or lactating women",
            "criterions": [
                {
                    "exact_snippets": "Pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "lactating women",
                    "criterion": "lactation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}