{
    "info": {
        "nct_id": "NCT00104091",
        "official_title": "A Multicenter Phase II Study of TP-38 in Those Patients With Glioblastoma Multiforme Who Have Recurred or Progressed After Previous Resection and Radiation Therapy and Are Scheduled for Gross Total Resection",
        "inclusion_criteria": "The patients must fulfill all the following criteria:\n\n* Previous histologically-confirmed diagnosis of primary GBM (glioblastoma multiforme, glioma grade 4 at time of first diagnosis).\n* Histologically-confirmed and MRI diagnosed recurrent or progressive GBM after previous resection (surgical or biopsy) and radiation therapy.\n* Medically capable of undergoing the planned surgical gross total resection and the catheter placement.\n* Age ≥ 18.\n* Karnofsky Performance Status of ≥ 70%.\n* Life expectancy of ≥ 3 months.\n* Patients must already be taking or begin taking corticosteroids at a stable dose of 4 mg every 6 hours for at least 72 hours prior to catheter placement.\n* Patients must be capable of taking, or already taking, anticonvulsant medication.\n* Patients must have read, signed, and dated an informed consent according to ICH-GCP, the local regulatory requirement and the rules followed at each institution.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "Patients fulfilling any of the following criteria should not be enrolled in the study:\n\n* Previous myelosuppressive chemotherapy within the past 4 weeks of the start of the infusion. Patients who have received more than two chemotherapy regimens (single therapy or combination therapy) are ineligible.\n* Any form of brain radiation within 10 weeks of the start of the infusion.\n* Previous gamma knife radiosurgery, stereotactic radiosurgery, and/or internal radiotherapy, unless the recurrence/progression is histologically confirmed (fine-needle biopsy).\n* Prior intracavitary biologic response modifiers or monoclonal antibodies.\n* Uncontrolled seizures.\n* Bilateral or multifocal tumors.\n* Evidence of cerebral uncal herniation.\n* Midline brain shift on MRI scan of > 0.5 cm prior to resection; patients with subfalcine herniation may be enrolled.\n* Tumors involving the brainstem or cerebellum.\n* Diffuse subependymal or CSF disease.\n* Women who are pregnant or breast feeding. All women of child-bearing potential should be excluded unless they have a negative pregnancy test and are using adequate contraceptive measures or are surgically sterile. Post-menopausal women must be amenorrheic for at least 12 months to be considered non-childbearing.\n* Fertile males not practicing adequate contraception and whose female partners are not using adequate contraceptive protection.\n* Prior or concurrent investigational treatment within 30 days of study entry.\n* Active infection requiring treatment or having an unexplained febrile illness.\n* Systemic diseases or other conditions which may be associated with unacceptable anesthetic/operative risk and/or which would not allow safe completion of this study protocol.\n* Prior or concurrent malignancy (curatively treated carcinoma-in-situ or basal cell carcinoma or patients who have been disease free for at least 5 years are eligible).",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Previous histologically-confirmed diagnosis of primary GBM (glioblastoma multiforme, glioma grade 4 at time of first diagnosis).",
            "criterions": [
                {
                    "exact_snippets": "Previous histologically-confirmed diagnosis of primary GBM (glioblastoma multiforme, glioma grade 4 at time of first diagnosis)",
                    "criterion": "primary GBM diagnosis",
                    "requirements": [
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": "histologically-confirmed"
                        },
                        {
                            "requirement_type": "grade",
                            "expected_value": "glioma grade 4"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Histologically-confirmed and MRI diagnosed recurrent or progressive GBM after previous resection (surgical or biopsy) and radiation therapy.",
            "criterions": [
                {
                    "exact_snippets": "Histologically-confirmed",
                    "criterion": "histological confirmation",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "MRI diagnosed",
                    "criterion": "MRI diagnosis",
                    "requirements": [
                        {
                            "requirement_type": "diagnosis",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "recurrent or progressive GBM",
                    "criterion": "GBM status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": [
                                "recurrent",
                                "progressive"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "after previous resection (surgical or biopsy)",
                    "criterion": "previous resection",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "surgical",
                                "biopsy"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "after ... radiation therapy",
                    "criterion": "previous radiation therapy",
                    "requirements": [
                        {
                            "requirement_type": "completion",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Medically capable of undergoing the planned surgical gross total resection and the catheter placement.",
            "criterions": [
                {
                    "exact_snippets": "Medically capable of undergoing the planned surgical gross total resection",
                    "criterion": "medical capability for surgical gross total resection",
                    "requirements": [
                        {
                            "requirement_type": "capability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Medically capable of undergoing ... the catheter placement",
                    "criterion": "medical capability for catheter placement",
                    "requirements": [
                        {
                            "requirement_type": "capability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Age ≥ 18.",
            "criterions": [
                {
                    "exact_snippets": "Age ≥ 18",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Karnofsky Performance Status of ≥ 70%.",
            "criterions": [
                {
                    "exact_snippets": "Karnofsky Performance Status of ≥ 70%",
                    "criterion": "Karnofsky Performance Status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 70,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "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": "* Patients must already be taking or begin taking corticosteroids at a stable dose of 4 mg every 6 hours for at least 72 hours prior to catheter placement.",
            "criterions": [
                {
                    "exact_snippets": "Patients must already be taking or begin taking corticosteroids",
                    "criterion": "corticosteroid usage",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "at a stable dose of 4 mg every 6 hours",
                    "criterion": "corticosteroid dosage",
                    "requirements": [
                        {
                            "requirement_type": "dosage",
                            "expected_value": {
                                "operator": "=",
                                "value": 4,
                                "unit": "mg every 6 hours"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "for at least 72 hours prior to catheter placement",
                    "criterion": "corticosteroid duration",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 72,
                                "unit": "hours"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must be capable of taking, or already taking, anticonvulsant medication.",
            "criterions": [
                {
                    "exact_snippets": "capable of taking, or already taking, anticonvulsant medication",
                    "criterion": "anticonvulsant medication",
                    "requirements": [
                        {
                            "requirement_type": "capability",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "current use",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must have read, signed, and dated an informed consent according to ICH-GCP, the local regulatory requirement and the rules followed at each institution.",
            "criterions": [
                {
                    "exact_snippets": "Patients must have read, signed, and dated an informed consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "completion",
                            "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": "* Previous myelosuppressive chemotherapy within the past 4 weeks of the start of the infusion. Patients who have received more than two chemotherapy regimens (single therapy or combination therapy) are ineligible.",
            "criterions": [
                {
                    "exact_snippets": "Previous myelosuppressive chemotherapy within the past 4 weeks of the start of the infusion.",
                    "criterion": "previous myelosuppressive chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients who have received more than two chemotherapy regimens (single therapy or combination therapy) are ineligible.",
                    "criterion": "number of chemotherapy regimens received",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "regimens"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any form of brain radiation within 10 weeks of the start of the infusion.",
            "criterions": [
                {
                    "exact_snippets": "Any form of brain radiation within 10 weeks of the start of the infusion.",
                    "criterion": "brain radiation",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 10,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Previous gamma knife radiosurgery, stereotactic radiosurgery, and/or internal radiotherapy, unless the recurrence/progression is histologically confirmed (fine-needle biopsy).",
            "criterions": [
                {
                    "exact_snippets": "Previous gamma knife radiosurgery",
                    "criterion": "previous gamma knife radiosurgery",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "stereotactic radiosurgery",
                    "criterion": "previous stereotactic radiosurgery",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "internal radiotherapy",
                    "criterion": "previous internal radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "recurrence/progression is histologically confirmed (fine-needle biopsy)",
                    "criterion": "histological confirmation of recurrence/progression",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prior intracavitary biologic response modifiers or monoclonal antibodies.",
            "criterions": [
                {
                    "exact_snippets": "Prior intracavitary biologic response modifiers",
                    "criterion": "intracavitary biologic response modifiers",
                    "requirements": [
                        {
                            "requirement_type": "prior use",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior ... monoclonal antibodies",
                    "criterion": "monoclonal antibodies",
                    "requirements": [
                        {
                            "requirement_type": "prior use",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Uncontrolled seizures.",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled seizures",
                    "criterion": "seizures",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Bilateral or multifocal tumors.",
            "criterions": [
                {
                    "exact_snippets": "Bilateral or multifocal tumors",
                    "criterion": "tumors",
                    "requirements": [
                        {
                            "requirement_type": "location",
                            "expected_value": [
                                "bilateral",
                                "multifocal"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Evidence of cerebral uncal herniation.",
            "criterions": [
                {
                    "exact_snippets": "Evidence of cerebral uncal herniation",
                    "criterion": "cerebral uncal herniation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Midline brain shift on MRI scan of > 0.5 cm prior to resection; patients with subfalcine herniation may be enrolled.",
            "criterions": [
                {
                    "exact_snippets": "Midline brain shift on MRI scan of > 0.5 cm",
                    "criterion": "midline brain shift",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">",
                                "value": 0.5,
                                "unit": "cm"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "subfalcine herniation",
                    "criterion": "subfalcine herniation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Tumors involving the brainstem or cerebellum.",
            "criterions": [
                {
                    "exact_snippets": "Tumors involving the brainstem",
                    "criterion": "tumors involving the brainstem",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Tumors involving the ... cerebellum",
                    "criterion": "tumors involving the cerebellum",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Diffuse subependymal or CSF disease.",
            "criterions": [
                {
                    "exact_snippets": "Diffuse subependymal",
                    "criterion": "subependymal disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "CSF disease",
                    "criterion": "CSF disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Women who are pregnant or breast feeding. All women of child-bearing potential should be excluded unless they have a negative pregnancy test and are using adequate contraceptive measures or are surgically sterile. Post-menopausal women must be amenorrheic for at least 12 months to be considered non-childbearing.",
            "criterions": [
                {
                    "exact_snippets": "Women who are pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "breast feeding",
                    "criterion": "breastfeeding",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "All women of child-bearing potential ... negative pregnancy test",
                    "criterion": "pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "All women of child-bearing potential ... using adequate contraceptive measures",
                    "criterion": "contraceptive measures",
                    "requirements": [
                        {
                            "requirement_type": "usage",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "All women of child-bearing potential ... surgically sterile",
                    "criterion": "surgical sterility",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Post-menopausal women must be amenorrheic for at least 12 months",
                    "criterion": "amenorrhea duration",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Fertile males not practicing adequate contraception and whose female partners are not using adequate contraceptive protection.",
            "criterions": [
                {
                    "exact_snippets": "Fertile males",
                    "criterion": "fertility",
                    "requirements": [
                        {
                            "requirement_type": "fertility",
                            "expected_value": "fertile"
                        }
                    ]
                },
                {
                    "exact_snippets": "not practicing adequate contraception",
                    "criterion": "contraception practice",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "female partners are not using adequate contraceptive protection",
                    "criterion": "female partner contraception",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prior or concurrent investigational treatment within 30 days of study entry.",
            "criterions": [
                {
                    "exact_snippets": "Prior or concurrent investigational treatment",
                    "criterion": "investigational treatment",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "prior or concurrent"
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 30,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Active infection requiring treatment or having an unexplained febrile illness.",
            "criterions": [
                {
                    "exact_snippets": "Active infection requiring treatment",
                    "criterion": "active infection",
                    "requirements": [
                        {
                            "requirement_type": "treatment requirement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "unexplained febrile illness",
                    "criterion": "febrile illness",
                    "requirements": [
                        {
                            "requirement_type": "explanation",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Systemic diseases or other conditions which may be associated with unacceptable anesthetic/operative risk and/or which would not allow safe completion of this study protocol.",
            "criterions": [
                {
                    "exact_snippets": "Systemic diseases or other conditions which may be associated with unacceptable anesthetic/operative risk",
                    "criterion": "systemic diseases or other conditions",
                    "requirements": [
                        {
                            "requirement_type": "anesthetic/operative risk",
                            "expected_value": "unacceptable"
                        }
                    ]
                },
                {
                    "exact_snippets": "Systemic diseases or other conditions ... which would not allow safe completion of this study protocol",
                    "criterion": "systemic diseases or other conditions",
                    "requirements": [
                        {
                            "requirement_type": "completion of study protocol",
                            "expected_value": "not safe"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prior or concurrent malignancy (curatively treated carcinoma-in-situ or basal cell carcinoma or patients who have been disease free for at least 5 years are eligible).",
            "criterions": [
                {
                    "exact_snippets": "Prior or concurrent malignancy",
                    "criterion": "malignancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "curatively treated carcinoma-in-situ",
                    "criterion": "carcinoma-in-situ",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "curatively treated"
                        }
                    ]
                },
                {
                    "exact_snippets": "curatively treated ... basal cell carcinoma",
                    "criterion": "basal cell carcinoma",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "curatively treated"
                        }
                    ]
                },
                {
                    "exact_snippets": "disease free for at least 5 years",
                    "criterion": "disease-free status",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 5,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [
        {
            "line": "The patients must fulfill all the following criteria:",
            "criterions": []
        }
    ],
    "failed_exclusion": [
        {
            "line": "Patients fulfilling any of the following criteria should not be enrolled in the study:",
            "criterions": []
        }
    ],
    "failed_miscellaneous": []
}