{
    "info": {
        "nct_id": "NCT00359294",
        "official_title": "A Phase I Multicenter, Open-label, Dose-escalating Clinical and Pharmacokinetic Study of PM00104 Administered Intravenously Over 1 Hour Daily for 5 Days, Every 3 Weeks, to Subjects With Advanced Malignant Solid Tumors or Lymphoma.",
        "inclusion_criteria": "1. Voluntary written informed consent of the subject obtained before any study-specific procedure.\n2. Histologically or cytologically confirmed malignant solid tumor or lymphoma.\n3. Subjects with malignancies that are not otherwise curable or for which no effective standard therapy exists.\n4. Age ≥ 18 years.\n5. Subject with measurable or non-measurable disease using the RECIST criteria\n6. Recovery from any drug-related adverse event related to previous treatment, excluding alopecia and NCI-CTCAE grade < 2 peripheral neuropathy.\n7. Laboratory values within 7 days prior to first infusion:\n\n   * Platelet count ≥ 100 x109/L, hemoglobin ≥ 9 g/dL and absolute neutrophil count (ANC) ≥ 1.5 x109/L.\n   * Alkaline phosphatase ≤ 2.5 x the upper limit of normal (ULN) (≤ 5 x ULN in case of extensive bone metastases)\n   * Aspartate aminotransferase (AST): ≤ 2.5 x ULN\n   * Alanine aminotransferase (ALT): ≤ 2.5 x ULN\n   * Total bilirubin: ≤ 1.5 ULN, unless due to Gilbert's syndrome.\n   * Creatinine: ≤ ULN, or calculated creatinine clearance: ≥ 60 mL/min (calculated from the Cockcroft-Gault formula; see Appendix III).\n   * Albumin: ≥ 2.5 g/dL.\n   * Partial thromboplastin within normal limits for the institution\n   * International normalized ratio (INR) within normal limits for the institution (unless due to oral anticoagulation)\n8. Performance status (ECOG) ≤ 1\n9. Life expectancy ≥ 3 months.\n10. Left ventricular ejection fraction (LVEF) within normal limits for the institution (LVEF of at least 50%).\n11. Women of childbearing potential must have a negative serum pregnancy test before study entry. Both men and women must agree to use a medically acceptable method of contraception throughout the treatment period and for 3 months after discontinuation of treatment. Acceptable methods of contraception include complete abstinence, Intrauterine device, oral contraceptive, subdermal implant and double barrier (condom with a contraceptive sponge or contraceptive suppository).\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "1. Prior therapy with PM00104\n2. Pregnant or lactating women.\n3. Less than 4 weeks from radiation therapy (8 weeks in case of extensive prior radiotherapy) or last dose of hormonal therapy, biological therapy or chemotherapy (6 weeks in case of nitrosourea, mitomycin C).\n4. Prior high dose chemotherapy that needed bone marrow transplant support.\n5. Subjects with untreated or uncontrolled brain or meningeal metastases.\n6. Other relevant diseases or adverse clinical conditions:\n\n   * Increased cardiac risk as defined by:\n\n     * History or presence of unstable angina.\n     * History or presence of myocardial infarction.\n     * Congestive heart failure.\n     * Symptomatic arrhythmia or any arrhythmia requiring ongoing treatment.\n     * Abnormal ECG (i.e., patients with the following are excluded: QT prolongation-corrected QT interval > 480 msec-, signs of cardiac enlargement or hypertrophy, bundle branch block, partial bundle branch blocks, signs of ischemia or necrosis, Wolff-Parkinson-White patterns).\n     * History or presence of valvular heart disease.\n     * Uncontrolled arterial hypertension despite optimal medical therapy.\n     * Previous mediastinal radiotherapy.\n     * Previous treatment with doxorubicin at cumulative doses in excess of 400 mg/m2\n   * History of significant neurological or psychiatric disorders.\n   * Active infection.\n   * Significant non-neoplastic liver disease (e.g., cirrhosis, chronic active hepatitis).\n   * Significant non-neoplastic renal disease.\n   * Immunocompromised subjects, including subjects known to be infected by human immunodeficiency virus (HIV).\n   * Uncontrolled endocrine diseases (e.g., diabetes mellitus, hypothyroidism or hyperthyroidism, adrenal disorder) requiring relevant changes in medication within the last month or hospital admission within the last 3 months.\n   * Any other major illness that, in the investigator's judgment, could substantially increase the risk associated with the subject's participation in this study.\n7. Limitation of the subject's ability to comply with the treatment or to follow-up at a participating center. Subjects registered on this trial must be treated and followed at a participating center.\n8. Treatment with any investigational product in the 30 days period prior to the first infusion.\n9. Known hypersensitivity to any of the components of the drug product, including sucrose or potassium phosphate.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Voluntary written informed consent of the subject obtained before any study-specific procedure.",
            "criterions": [
                {
                    "exact_snippets": "Voluntary written informed consent of the subject obtained",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Histologically or cytologically confirmed malignant solid tumor or lymphoma.",
            "criterions": [
                {
                    "exact_snippets": "Histologically or cytologically confirmed malignant solid tumor",
                    "criterion": "malignant solid tumor",
                    "requirements": [
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": [
                                "histologically",
                                "cytologically"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Histologically or cytologically confirmed ... lymphoma",
                    "criterion": "lymphoma",
                    "requirements": [
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": [
                                "histologically",
                                "cytologically"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Subjects with malignancies that are not otherwise curable or for which no effective standard therapy exists.",
            "criterions": [
                {
                    "exact_snippets": "malignancies that are not otherwise curable",
                    "criterion": "malignancies",
                    "requirements": [
                        {
                            "requirement_type": "curability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "no effective standard therapy exists",
                    "criterion": "malignancies",
                    "requirements": [
                        {
                            "requirement_type": "effective standard therapy",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Age ≥ 18 years.",
            "criterions": [
                {
                    "exact_snippets": "Age ≥ 18 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Subject with measurable or non-measurable disease using the RECIST criteria",
            "criterions": [
                {
                    "exact_snippets": "measurable or non-measurable disease using the RECIST criteria",
                    "criterion": "disease measurability",
                    "requirements": [
                        {
                            "requirement_type": "criteria",
                            "expected_value": [
                                "measurable",
                                "non-measurable"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Recovery from any drug-related adverse event related to previous treatment, excluding alopecia and NCI-CTCAE grade < 2 peripheral neuropathy.",
            "criterions": [
                {
                    "exact_snippets": "Recovery from any drug-related adverse event related to previous treatment",
                    "criterion": "recovery from drug-related adverse event",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "excluding alopecia",
                    "criterion": "alopecia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "excluding ... NCI-CTCAE grade < 2 peripheral neuropathy",
                    "criterion": "peripheral neuropathy",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<",
                                "value": 2,
                                "unit": "NCI-CTCAE grade"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Laboratory values within 7 days prior to first infusion:",
            "criterions": [
                {
                    "exact_snippets": "Laboratory values within 7 days prior to first infusion",
                    "criterion": "laboratory values",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "within 7 days prior to first infusion"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Platelet count ≥ 100 x109/L, hemoglobin ≥ 9 g/dL and absolute neutrophil count (ANC) ≥ 1.5 x109/L.",
            "criterions": [
                {
                    "exact_snippets": "Platelet count ≥ 100 x109/L",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100,
                                "unit": "x109/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "hemoglobin ≥ 9 g/dL",
                    "criterion": "hemoglobin",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 9,
                                "unit": "g/dL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "absolute neutrophil count (ANC) ≥ 1.5 x109/L",
                    "criterion": "absolute neutrophil count (ANC)",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.5,
                                "unit": "x109/L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Alkaline phosphatase ≤ 2.5 x the upper limit of normal (ULN) (≤ 5 x ULN in case of extensive bone metastases)",
            "criterions": [
                {
                    "exact_snippets": "Alkaline phosphatase ≤ 2.5 x the upper limit of normal (ULN)",
                    "criterion": "alkaline phosphatase",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Alkaline phosphatase ... ≤ 5 x ULN in case of extensive bone metastases",
                    "criterion": "alkaline phosphatase in case of extensive bone metastases",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Aspartate aminotransferase (AST): ≤ 2.5 x ULN",
            "criterions": [
                {
                    "exact_snippets": "Aspartate aminotransferase (AST): ≤ 2.5 x ULN",
                    "criterion": "Aspartate aminotransferase (AST)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Alanine aminotransferase (ALT): ≤ 2.5 x ULN",
            "criterions": [
                {
                    "exact_snippets": "Alanine aminotransferase (ALT): ≤ 2.5 x ULN",
                    "criterion": "Alanine aminotransferase (ALT)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Total bilirubin: ≤ 1.5 ULN, unless due to Gilbert's syndrome.",
            "criterions": [
                {
                    "exact_snippets": "Total bilirubin: ≤ 1.5 ULN",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "unless due to Gilbert's syndrome",
                    "criterion": "Gilbert's syndrome",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Creatinine: ≤ ULN, or calculated creatinine clearance: ≥ 60 mL/min (calculated from the Cockcroft-Gault formula; see Appendix III).",
            "criterions": [
                {
                    "exact_snippets": "Creatinine: ≤ ULN",
                    "criterion": "creatinine",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "calculated creatinine clearance: ≥ 60 mL/min",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 60,
                                "unit": "mL/min"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Albumin: ≥ 2.5 g/dL.",
            "criterions": [
                {
                    "exact_snippets": "Albumin: ≥ 2.5 g/dL.",
                    "criterion": "albumin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2.5,
                                "unit": "g/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Partial thromboplastin within normal limits for the institution",
            "criterions": [
                {
                    "exact_snippets": "Partial thromboplastin within normal limits for the institution",
                    "criterion": "partial thromboplastin",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": "within normal limits for the institution"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* International normalized ratio (INR) within normal limits for the institution (unless due to oral anticoagulation)",
            "criterions": [
                {
                    "exact_snippets": "International normalized ratio (INR) within normal limits for the institution",
                    "criterion": "INR",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": "within normal limits for the institution"
                        }
                    ]
                },
                {
                    "exact_snippets": "unless due to oral anticoagulation",
                    "criterion": "oral anticoagulation",
                    "requirements": [
                        {
                            "requirement_type": "cause of INR deviation",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Performance status (ECOG) ≤ 1",
            "criterions": [
                {
                    "exact_snippets": "Performance status (ECOG) ≤ 1",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "N/A"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Life expectancy ≥ 3 months.",
            "criterions": [
                {
                    "exact_snippets": "Life expectancy ≥ 3 months.",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Left ventricular ejection fraction (LVEF) within normal limits for the institution (LVEF of at least 50%).",
            "criterions": [
                {
                    "exact_snippets": "Left ventricular ejection fraction (LVEF) within normal limits for the institution (LVEF of at least 50%)",
                    "criterion": "left ventricular ejection fraction (LVEF)",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 50,
                                        "unit": "%"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Women of childbearing potential must have a negative serum pregnancy test before study entry. Both men and women must agree to use a medically acceptable method of contraception throughout the treatment period and for 3 months after discontinuation of treatment. Acceptable methods of contraception include complete abstinence, Intrauterine device, oral contraceptive, subdermal implant and double barrier (condom with a contraceptive sponge or contraceptive suppository).",
            "criterions": [
                {
                    "exact_snippets": "Women of childbearing potential",
                    "criterion": "women of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "negative serum pregnancy test before study entry",
                    "criterion": "serum pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "Both men and women must agree to use a medically acceptable method of contraception throughout the treatment period and for 3 months after discontinuation of treatment",
                    "criterion": "use of contraception",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "throughout the treatment period and for 3 months after discontinuation of treatment"
                        }
                    ]
                },
                {
                    "exact_snippets": "Acceptable methods of contraception include complete abstinence, Intrauterine device, oral contraceptive, subdermal implant and double barrier (condom with a contraceptive sponge or contraceptive suppository)",
                    "criterion": "methods of contraception",
                    "requirements": [
                        {
                            "requirement_type": "acceptable methods",
                            "expected_value": [
                                "complete abstinence",
                                "Intrauterine device",
                                "oral contraceptive",
                                "subdermal implant",
                                "double barrier (condom with a contraceptive sponge or contraceptive suppository)"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "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": "1. Prior therapy with PM00104",
            "criterions": [
                {
                    "exact_snippets": "Prior therapy with PM00104",
                    "criterion": "therapy with PM00104",
                    "requirements": [
                        {
                            "requirement_type": "prior",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. 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
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Prior high dose chemotherapy that needed bone marrow transplant support.",
            "criterions": [
                {
                    "exact_snippets": "Prior high dose chemotherapy",
                    "criterion": "high dose chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "prior treatment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "needed bone marrow transplant support",
                    "criterion": "bone marrow transplant support",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Subjects with untreated or uncontrolled brain or meningeal metastases.",
            "criterions": [
                {
                    "exact_snippets": "untreated or uncontrolled brain or meningeal metastases",
                    "criterion": "brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": [
                                "untreated",
                                "uncontrolled"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "untreated or uncontrolled brain or meningeal metastases",
                    "criterion": "meningeal metastases",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": [
                                "untreated",
                                "uncontrolled"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Other relevant diseases or adverse clinical conditions:",
            "criterions": [
                {
                    "exact_snippets": "Other relevant diseases or adverse clinical conditions",
                    "criterion": "relevant diseases or adverse clinical conditions",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Increased cardiac risk as defined by:",
            "criterions": [
                {
                    "exact_snippets": "Increased cardiac risk",
                    "criterion": "cardiac risk",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "increased"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History or presence of unstable angina.",
            "criterions": [
                {
                    "exact_snippets": "History or presence of unstable angina",
                    "criterion": "unstable angina",
                    "requirements": [
                        {
                            "requirement_type": "history or presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History or presence of myocardial infarction.",
            "criterions": [
                {
                    "exact_snippets": "History ... of myocardial infarction.",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "presence of myocardial infarction.",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Congestive heart failure.",
            "criterions": [
                {
                    "exact_snippets": "Congestive heart failure",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Symptomatic arrhythmia or any arrhythmia requiring ongoing treatment.",
            "criterions": [
                {
                    "exact_snippets": "Symptomatic arrhythmia",
                    "criterion": "arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "symptomatic",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "any arrhythmia requiring ongoing treatment",
                    "criterion": "arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "treatment requirement",
                            "expected_value": "ongoing"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Abnormal ECG (i.e., patients with the following are excluded: QT prolongation-corrected QT interval > 480 msec-, signs of cardiac enlargement or hypertrophy, bundle branch block, partial bundle branch blocks, signs of ischemia or necrosis, Wolff-Parkinson-White patterns).",
            "criterions": [
                {
                    "exact_snippets": "Abnormal ECG ... QT prolongation-corrected QT interval > 480 msec",
                    "criterion": "QT prolongation-corrected QT interval",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">",
                                "value": 480,
                                "unit": "msec"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Abnormal ECG ... signs of cardiac enlargement or hypertrophy",
                    "criterion": "signs of cardiac enlargement or hypertrophy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Abnormal ECG ... bundle branch block",
                    "criterion": "bundle branch block",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Abnormal ECG ... partial bundle branch blocks",
                    "criterion": "partial bundle branch blocks",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Abnormal ECG ... signs of ischemia or necrosis",
                    "criterion": "signs of ischemia or necrosis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Abnormal ECG ... Wolff-Parkinson-White patterns",
                    "criterion": "Wolff-Parkinson-White patterns",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History or presence of valvular heart disease.",
            "criterions": [
                {
                    "exact_snippets": "History or presence of valvular heart disease.",
                    "criterion": "valvular heart disease",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Uncontrolled arterial hypertension despite optimal medical therapy.",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled arterial hypertension despite optimal medical therapy.",
                    "criterion": "arterial hypertension",
                    "requirements": [
                        {
                            "requirement_type": "control status",
                            "expected_value": "uncontrolled"
                        },
                        {
                            "requirement_type": "treatment",
                            "expected_value": "optimal medical therapy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Previous mediastinal radiotherapy.",
            "criterions": [
                {
                    "exact_snippets": "Previous mediastinal radiotherapy",
                    "criterion": "mediastinal radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Previous treatment with doxorubicin at cumulative doses in excess of 400 mg/m2",
            "criterions": [
                {
                    "exact_snippets": "Previous treatment with doxorubicin at cumulative doses in excess of 400 mg/m2",
                    "criterion": "doxorubicin treatment",
                    "requirements": [
                        {
                            "requirement_type": "cumulative dose",
                            "expected_value": {
                                "operator": ">",
                                "value": 400,
                                "unit": "mg/m2"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of significant neurological or psychiatric disorders.",
            "criterions": [
                {
                    "exact_snippets": "History of significant neurological ... disorders.",
                    "criterion": "neurological disorders",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "severity",
                            "expected_value": "significant"
                        }
                    ]
                },
                {
                    "exact_snippets": "History of significant ... psychiatric disorders.",
                    "criterion": "psychiatric disorders",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "severity",
                            "expected_value": "significant"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Active infection.",
            "criterions": [
                {
                    "exact_snippets": "Active infection.",
                    "criterion": "infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Significant non-neoplastic liver disease (e.g., cirrhosis, chronic active hepatitis).",
            "criterions": [
                {
                    "exact_snippets": "Significant non-neoplastic liver disease (e.g., cirrhosis, chronic active hepatitis)",
                    "criterion": "non-neoplastic liver disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "significant"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Significant non-neoplastic renal disease.",
            "criterions": [
                {
                    "exact_snippets": "Significant non-neoplastic renal disease",
                    "criterion": "non-neoplastic renal disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "significant"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Immunocompromised subjects, including subjects known to be infected by human immunodeficiency virus (HIV).",
            "criterions": [
                {
                    "exact_snippets": "Immunocompromised subjects",
                    "criterion": "immunocompromised status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "subjects known to be infected by human immunodeficiency virus (HIV)",
                    "criterion": "HIV infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Uncontrolled endocrine diseases (e.g., diabetes mellitus, hypothyroidism or hyperthyroidism, adrenal disorder) requiring relevant changes in medication within the last month or hospital admission within the last 3 months.",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled endocrine diseases (e.g., diabetes mellitus, hypothyroidism or hyperthyroidism, adrenal disorder)",
                    "criterion": "endocrine diseases",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": "uncontrolled"
                        }
                    ]
                },
                {
                    "exact_snippets": "requiring relevant changes in medication within the last month",
                    "criterion": "medication changes",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within the last month"
                        }
                    ]
                },
                {
                    "exact_snippets": "hospital admission within the last 3 months",
                    "criterion": "hospital admission",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within the last 3 months"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any other major illness that, in the investigator's judgment, could substantially increase the risk associated with the subject's participation in this study.",
            "criterions": [
                {
                    "exact_snippets": "Any other major illness ... could substantially increase the risk",
                    "criterion": "major illness",
                    "requirements": [
                        {
                            "requirement_type": "risk assessment",
                            "expected_value": "substantially increase the risk associated with the subject's participation"
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Limitation of the subject's ability to comply with the treatment or to follow-up at a participating center. Subjects registered on this trial must be treated and followed at a participating center.",
            "criterions": [
                {
                    "exact_snippets": "Limitation of the subject's ability to comply with the treatment",
                    "criterion": "ability to comply with treatment",
                    "requirements": [
                        {
                            "requirement_type": "limitation",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Limitation of the subject's ability ... to follow-up at a participating center",
                    "criterion": "ability to follow-up at a participating center",
                    "requirements": [
                        {
                            "requirement_type": "limitation",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Subjects registered on this trial must be treated ... at a participating center",
                    "criterion": "treatment at a participating center",
                    "requirements": [
                        {
                            "requirement_type": "requirement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Subjects registered on this trial must be ... followed at a participating center",
                    "criterion": "follow-up at a participating center",
                    "requirements": [
                        {
                            "requirement_type": "requirement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Treatment with any investigational product in the 30 days period prior to the first infusion.",
            "criterions": [
                {
                    "exact_snippets": "Treatment with any investigational product in the 30 days period prior to the first infusion.",
                    "criterion": "treatment with investigational product",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 30,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Known hypersensitivity to any of the components of the drug product, including sucrose or potassium phosphate.",
            "criterions": [
                {
                    "exact_snippets": "Known hypersensitivity to any of the components of the drug product",
                    "criterion": "hypersensitivity to drug components",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "hypersensitivity to ... sucrose",
                    "criterion": "hypersensitivity to sucrose",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "hypersensitivity to ... potassium phosphate",
                    "criterion": "hypersensitivity to potassium phosphate",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [
        {
            "line": "3. Less than 4 weeks from radiation therapy (8 weeks in case of extensive prior radiotherapy) or last dose of hormonal therapy, biological therapy or chemotherapy (6 weeks in case of nitrosourea, mitomycin C).",
            "criterions": [
                {
                    "exact_snippets": "Less than 4 weeks from radiation therapy (8 weeks in case of extensive prior radiotherapy)",
                    "criterion": "time since radiation therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since treatment",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Less than 4 weeks from radiation therapy (8 weeks in case of extensive prior radiotherapy)",
                    "criterion": "time since extensive prior radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since treatment",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<",
                                        "value": 8,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Less than 4 weeks from ... last dose of hormonal therapy",
                    "criterion": "time since last dose of hormonal therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since treatment",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Less than 4 weeks from ... last dose of biological therapy",
                    "criterion": "time since last dose of biological therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since treatment",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Less than 4 weeks from ... last dose of chemotherapy (6 weeks in case of nitrosourea, mitomycin C)",
                    "criterion": "time since last dose of chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since treatment",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Less than 4 weeks from ... last dose of chemotherapy (6 weeks in case of nitrosourea, mitomycin C)",
                    "criterion": "time since last dose of nitrosourea or mitomycin C",
                    "requirements": [
                        {
                            "requirement_type": "time since treatment",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<",
                                        "value": 6,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "failed_miscellaneous": []
}