{
    "info": {
        "nct_id": "NCT01484860",
        "official_title": "A Phase II Single Arm Study of AUY922 in Patients With Metastatic Pancreatic Adenocarcinoma Who Are Resistant to First Line Chemotherapy",
        "inclusion_criteria": "* Histologically or cytologically confirmed diagnosis of adenocarcinoma of the pancreas with metastatic disease\n* Patients have received at least one prior systemic anticancer therapy for their advanced disease, which may include a gemcitabine based or 5-FU based therapeutic regimen. Patients with resected disease who relapse within 6 months of completion of adjuvant gemcitabine would also be eligible.\n* Patients with progressive disease (radiological confirmation required) after at least one line of chemotherapy for pancreatic adenocarcinoma. Patients must have at least one measurable lesion as defined by RECIST criteria. Irradiated lesions are only evaluable for disease progression.\n* Patient's age is ≥ 18 years of age\n* Patients may have received prior radiation treatment for management of local disease providing that disease progression has been documented, all toxicities have resolved, to ≤ grade 1 and the last fraction of radiation treatment was completed at least 4 weeks prior to randomization (2 weeks for palliative radiotherapy).\n* ECOG performance status of 0 or 1.\n* Life expectancy of greater than 12 weeks\n* Patients must have following laboratory values within 7 days prior to starting treatment:\n\n  * Hematological:\n  * Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L\n  * Hemoglobin (Hgb) ≥ 90 g/L\n  * Platelets (plt) ≥ 100 x 109/L\n  * Biochemistry:\n  * Potassium within normal limits\n  * Total calcium (corrected for serum albumin) and Phosphorus within normal limits\n  * Magnesium above LLN or correctable with supplements\n  * Adequate liver function defined as:\n  * AST/SGOT and ALT/SGPT ≤ 1.5 x Upper Limit of Normal (ULN)\n  * AST/SGOT and ALT/SGPT ≤ 2.5 x Upper Limit of Normal (ULN) if liver metastases are present\n  * Serum bilirubin ≤ 1.5 x ULN\n  * eGFR ≥ 50 mL /min\n* Women of childbearing potential (WOCBP) must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to randomization. Postmenopausal women must have been amenorrheic for ≥ 24 months in order to be considered \"of non-childbearing potential\". This should be documented appropriately in the patient's medical history.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Patients with a history of another primary malignancy that is clinically significant or requires active intervention\n* Prior treatment with any HSP90 or HDAC inhibitor compounds, including valproic acid\n* Patients with a significant history of cardiac disease, including:\n\n  * Impaired cardiac function, including any one of the following:\n  * History (or family history) of long QT syndrome\n  * Mean QTc ≥ 450 msec on baseline ECG\n  * History of clinically manifested ischemic heart disease ≤ 6 months prior to study start\n  * History of heart failure or left ventricular (LV) dysfunction (LVEF ≤ 45%) by MUGA or ECHO\n  * Clinically significant ECG abnormalities\n  * History or presence of atrial fibrillation, atrial flutter or ventricular arrhythmias including ventricular tachycardia or Torsades de Pointes\n  * Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)\n  * Clinically significant resting bradycardia (< 50 beats per minute)\n  * Patients who are currently receiving treatment with any medication which has a relative risk of prolonging the QTc interval or inducing Torsades de Pointes and cannot be switched to an alternative drug or discontinued prior to commencing start of treatment.\n  * Obligate use of a cardiac pacemaker\n* Patients with a serious active infection at the time of registration or other serious underlying medical conditions that would impair the ability of the patient to receive protocol treatment.\n* Patients with a known central nervous system metastases. CT scan of the brain is NOT required unless there is suspicion of CNS metastases.\n* Patients with any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol.\n* Pregnant or lactating females.\n* Women of child bearing potential or sexually active males who are not employing adequate contraception. Adequate methods of contraception include use of oral contraceptives or Depot-Provera, with an additional barrier method (diaphragm with spermicidal gel OR condoms with spermicide); a double-barrier method (diaphragm with spermicidal gel AND condoms with spermicide); partner vasectomy and total abstinence.\n* Patients who received systemic anti-cancer treatment prior to the first dose of study medication within the following time frames:\n\n  * Radiotherapy, conventional chemotherapy: within 4 weeks\n  * Palliative radiotherapy: within 2 weeks\n  * Monoclonal antibodies: within 4 weeks\n  * Nitrosoureas and mitomycin: within 6 weeks\n  * Targeted agents or investigational dugs: within 4 weeks\n* Patients who have had any surgery within 2 weeks prior to registration or who have not recovered from such therapy.\n* Patients known to be HIV positive. Testing is not required in the absence of clinical signs and symptoms suggestive of HIV infection.\n* Treatment with therapeutic doses of coumarin-type anticoagulants. (Maximum daily dose of 2 mg, for line patency permitted)\n* Patients with known disorders due to a deficiency in bilirubin glucuronidation (e.g. Gilbert's syndrome)\n* Unresolved diarrhea ≥ CTCAE grade 2 within 72 hours prior to registration\n* Patients with acute or chronic renal disease. Chronic renal disease will be defined as patients who have stable creatinine ≥ to 1.5 ULN and/or eGFR ≤ 50mL/min. Acute renal disease will be defined as patients that have an acute (within less then 4 weeks) rise in creatinine to ≥ 1.5 ULN and/or eGFR ≤ 50mL/min, that has not resolved to the previously normal baseline levels.\n* Patients with active liver disease that requires intervention.\n* Patients who cannot give informed consent (i.e. mentally incompetent patients, or those physically incapacitated such as comatose patients). Patients competent but physically unable to sign the consent form may have the document signed by their nearest relative or legal guardian. Each patient will be provided with a full explanation of the study before consent is requested.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Histologically or cytologically confirmed diagnosis of adenocarcinoma of the pancreas with metastatic disease",
            "criterions": [
                {
                    "exact_snippets": "Histologically or cytologically confirmed diagnosis of adenocarcinoma of the pancreas",
                    "criterion": "adenocarcinoma of the pancreas",
                    "requirements": [
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": [
                                "histologically",
                                "cytologically"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "metastatic disease",
                    "criterion": "metastatic disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients have received at least one prior systemic anticancer therapy for their advanced disease, which may include a gemcitabine based or 5-FU based therapeutic regimen. Patients with resected disease who relapse within 6 months of completion of adjuvant gemcitabine would also be eligible.",
            "criterions": [
                {
                    "exact_snippets": "Patients have received at least one prior systemic anticancer therapy",
                    "criterion": "prior systemic anticancer therapy",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "therapy"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "which may include a gemcitabine based or 5-FU based therapeutic regimen",
                    "criterion": "type of prior systemic anticancer therapy",
                    "requirements": [
                        {
                            "requirement_type": "inclusion",
                            "expected_value": [
                                "gemcitabine based",
                                "5-FU based"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients with resected disease who relapse within 6 months of completion of adjuvant gemcitabine",
                    "criterion": "relapse after adjuvant gemcitabine",
                    "requirements": [
                        {
                            "requirement_type": "time since completion",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with progressive disease (radiological confirmation required) after at least one line of chemotherapy for pancreatic adenocarcinoma. Patients must have at least one measurable lesion as defined by RECIST criteria. Irradiated lesions are only evaluable for disease progression.",
            "criterions": [
                {
                    "exact_snippets": "progressive disease (radiological confirmation required)",
                    "criterion": "progressive disease",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": "radiological"
                        }
                    ]
                },
                {
                    "exact_snippets": "at least one line of chemotherapy for pancreatic adenocarcinoma",
                    "criterion": "chemotherapy for pancreatic adenocarcinoma",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "line"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "at least one measurable lesion as defined by RECIST criteria",
                    "criterion": "measurable lesion",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "lesion"
                            }
                        },
                        {
                            "requirement_type": "definition",
                            "expected_value": "RECIST criteria"
                        }
                    ]
                },
                {
                    "exact_snippets": "Irradiated lesions are only evaluable for disease progression",
                    "criterion": "irradiated lesions",
                    "requirements": [
                        {
                            "requirement_type": "evaluable for",
                            "expected_value": "disease progression"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patient's age is ≥ 18 years of age",
            "criterions": [
                {
                    "exact_snippets": "Patient's age is ≥ 18 years of age",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients may have received prior radiation treatment for management of local disease providing that disease progression has been documented, all toxicities have resolved, to ≤ grade 1 and the last fraction of radiation treatment was completed at least 4 weeks prior to randomization (2 weeks for palliative radiotherapy).",
            "criterions": [
                {
                    "exact_snippets": "Patients may have received prior radiation treatment",
                    "criterion": "prior radiation treatment",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "disease progression has been documented",
                    "criterion": "disease progression documentation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "all toxicities have resolved, to ≤ grade 1",
                    "criterion": "toxicity resolution",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "the last fraction of radiation treatment was completed at least 4 weeks prior to randomization",
                    "criterion": "time since last radiation treatment",
                    "requirements": [
                        {
                            "requirement_type": "time elapsed",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "2 weeks for palliative radiotherapy",
                    "criterion": "time since last palliative radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time elapsed",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* ECOG performance status of 0 or 1.",
            "criterions": [
                {
                    "exact_snippets": "ECOG performance status of 0 or 1",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": [
                                "0",
                                "1"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Life expectancy of greater than 12 weeks",
            "criterions": [
                {
                    "exact_snippets": "Life expectancy of greater than 12 weeks",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 12,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must have following laboratory values within 7 days prior to starting treatment:",
            "criterions": [
                {
                    "exact_snippets": "laboratory values",
                    "criterion": "laboratory values",
                    "requirements": [
                        {
                            "requirement_type": "timeframe",
                            "expected_value": "within 7 days prior to starting treatment"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Hematological:",
            "criterions": [
                {
                    "exact_snippets": "Hematological",
                    "criterion": "hematological status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L",
            "criterions": [
                {
                    "exact_snippets": "Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L",
                    "criterion": "Absolute Neutrophil Count (ANC)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.5,
                                "unit": "x 10^9/L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Hemoglobin (Hgb) ≥ 90 g/L",
            "criterions": [
                {
                    "exact_snippets": "Hemoglobin (Hgb) ≥ 90 g/L",
                    "criterion": "hemoglobin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 90,
                                "unit": "g/L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Platelets (plt) ≥ 100 x 109/L",
            "criterions": [
                {
                    "exact_snippets": "Platelets (plt) ≥ 100 x 109/L",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100,
                                "unit": "x 109/L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Biochemistry:",
            "criterions": [
                {
                    "exact_snippets": "Biochemistry",
                    "criterion": "biochemistry",
                    "requirements": [
                        {
                            "requirement_type": "N/A",
                            "expected_value": "N/A"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Potassium within normal limits",
            "criterions": [
                {
                    "exact_snippets": "Potassium within normal limits",
                    "criterion": "potassium level",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": "within normal limits"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Total calcium (corrected for serum albumin) and Phosphorus within normal limits",
            "criterions": [
                {
                    "exact_snippets": "Total calcium (corrected for serum albumin) ... within normal limits",
                    "criterion": "total calcium",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": "within normal limits"
                        }
                    ]
                },
                {
                    "exact_snippets": "Phosphorus within normal limits",
                    "criterion": "phosphorus",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": "within normal limits"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Magnesium above LLN or correctable with supplements",
            "criterions": [
                {
                    "exact_snippets": "Magnesium above LLN",
                    "criterion": "magnesium level",
                    "requirements": [
                        {
                            "requirement_type": "comparison",
                            "expected_value": {
                                "operator": ">",
                                "value": 0,
                                "unit": "LLN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "correctable with supplements",
                    "criterion": "magnesium level",
                    "requirements": [
                        {
                            "requirement_type": "correctability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate liver function defined as:",
            "criterions": [
                {
                    "exact_snippets": "Adequate liver function",
                    "criterion": "liver function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* AST/SGOT and ALT/SGPT ≤ 1.5 x Upper Limit of Normal (ULN)",
            "criterions": [
                {
                    "exact_snippets": "AST/SGOT ... ≤ 1.5 x Upper Limit of Normal (ULN)",
                    "criterion": "AST/SGOT",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "ALT/SGPT ≤ 1.5 x Upper Limit of Normal (ULN)",
                    "criterion": "ALT/SGPT",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* AST/SGOT and ALT/SGPT ≤ 2.5 x Upper Limit of Normal (ULN) if liver metastases are present",
            "criterions": [
                {
                    "exact_snippets": "AST/SGOT ... ≤ 2.5 x Upper Limit of Normal (ULN) if liver metastases are present",
                    "criterion": "AST/SGOT",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "ALT/SGPT ≤ 2.5 x Upper Limit of Normal (ULN) if liver metastases are present",
                    "criterion": "ALT/SGPT",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "liver metastases are present",
                    "criterion": "liver metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Serum bilirubin ≤ 1.5 x ULN",
            "criterions": [
                {
                    "exact_snippets": "Serum bilirubin ≤ 1.5 x ULN",
                    "criterion": "serum bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* eGFR ≥ 50 mL /min",
            "criterions": [
                {
                    "exact_snippets": "eGFR ≥ 50 mL /min",
                    "criterion": "eGFR",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 50,
                                "unit": "mL/min"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Women of childbearing potential (WOCBP) must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to randomization. Postmenopausal women must have been amenorrheic for ≥ 24 months in order to be considered \"of non-childbearing potential\". This should be documented appropriately in the patient's medical history.",
            "criterions": [
                {
                    "exact_snippets": "Women of childbearing potential (WOCBP) must have a negative serum pregnancy test",
                    "criterion": "serum pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "minimum sensitivity 25 IU/L or equivalent units of HCG",
                    "criterion": "serum pregnancy test sensitivity",
                    "requirements": [
                        {
                            "requirement_type": "sensitivity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 25,
                                "unit": "IU/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "within 72 hours prior to randomization",
                    "criterion": "timing of serum pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "within 72 hours prior to randomization"
                        }
                    ]
                },
                {
                    "exact_snippets": "Postmenopausal women must have been amenorrheic for ≥ 24 months",
                    "criterion": "amenorrhea duration",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 24,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "This should be documented appropriately in the patient's medical history",
                    "criterion": "documentation in medical history",
                    "requirements": [
                        {
                            "requirement_type": "documentation",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have minimum age of 18 Years",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 18 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "* Patients with a history of another primary malignancy that is clinically significant or requires active intervention",
            "criterions": [
                {
                    "exact_snippets": "history of another primary malignancy",
                    "criterion": "history of another primary malignancy",
                    "requirements": [
                        {
                            "requirement_type": "clinical significance",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "active intervention requirement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prior treatment with any HSP90 or HDAC inhibitor compounds, including valproic acid",
            "criterions": [
                {
                    "exact_snippets": "Prior treatment with any HSP90 or HDAC inhibitor compounds, including valproic acid",
                    "criterion": "prior treatment with HSP90 or HDAC inhibitor compounds",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with a significant history of cardiac disease, including:",
            "criterions": [
                {
                    "exact_snippets": "significant history of cardiac disease",
                    "criterion": "cardiac disease",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": "significant"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Impaired cardiac function, including any one of the following:",
            "criterions": [
                {
                    "exact_snippets": "Impaired cardiac function",
                    "criterion": "cardiac function",
                    "requirements": [
                        {
                            "requirement_type": "condition",
                            "expected_value": "impaired"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History (or family history) of long QT syndrome",
            "criterions": [
                {
                    "exact_snippets": "History (or family history) of long QT syndrome",
                    "criterion": "long QT syndrome",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "family history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Mean QTc ≥ 450 msec on baseline ECG",
            "criterions": [
                {
                    "exact_snippets": "Mean QTc ≥ 450 msec on baseline ECG",
                    "criterion": "QTc interval",
                    "requirements": [
                        {
                            "requirement_type": "mean value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 450,
                                "unit": "msec"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of clinically manifested ischemic heart disease ≤ 6 months prior to study start",
            "criterions": [
                {
                    "exact_snippets": "History of clinically manifested ischemic heart disease ≤ 6 months prior to study start",
                    "criterion": "ischemic heart disease",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time since manifestation",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of heart failure or left ventricular (LV) dysfunction (LVEF ≤ 45%) by MUGA or ECHO",
            "criterions": [
                {
                    "exact_snippets": "History of heart failure",
                    "criterion": "heart failure",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "left ventricular (LV) dysfunction",
                    "criterion": "left ventricular dysfunction",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "LVEF ≤ 45%",
                    "criterion": "left ventricular ejection fraction (LVEF)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<=",
                                "value": 45,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Clinically significant ECG abnormalities",
            "criterions": [
                {
                    "exact_snippets": "Clinically significant ECG abnormalities",
                    "criterion": "ECG abnormalities",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "clinically significant"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History or presence of atrial fibrillation, atrial flutter or ventricular arrhythmias including ventricular tachycardia or Torsades de Pointes",
            "criterions": [
                {
                    "exact_snippets": "History or presence of atrial fibrillation",
                    "criterion": "atrial fibrillation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "History or presence of ... atrial flutter",
                    "criterion": "atrial flutter",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "History or presence of ... ventricular arrhythmias",
                    "criterion": "ventricular arrhythmias",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "History or presence of ... ventricular tachycardia",
                    "criterion": "ventricular tachycardia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "History or presence of ... Torsades de Pointes",
                    "criterion": "Torsades de Pointes",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)",
            "criterions": [
                {
                    "exact_snippets": "Other clinically significant heart disease",
                    "criterion": "clinically significant heart disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "congestive heart failure",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled hypertension",
                    "criterion": "uncontrolled hypertension",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "history of labile hypertension",
                    "criterion": "history of labile hypertension",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "history of poor compliance with an antihypertensive regimen",
                    "criterion": "history of poor compliance with an antihypertensive regimen",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Clinically significant resting bradycardia (< 50 beats per minute)",
            "criterions": [
                {
                    "exact_snippets": "Clinically significant resting bradycardia (< 50 beats per minute)",
                    "criterion": "resting bradycardia",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "clinically significant"
                        },
                        {
                            "requirement_type": "heart rate",
                            "expected_value": {
                                "operator": "<",
                                "value": 50,
                                "unit": "beats per minute"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who are currently receiving treatment with any medication which has a relative risk of prolonging the QTc interval or inducing Torsades de Pointes and cannot be switched to an alternative drug or discontinued prior to commencing start of treatment.",
            "criterions": [
                {
                    "exact_snippets": "currently receiving treatment with any medication which has a relative risk of prolonging the QTc interval",
                    "criterion": "medication with risk of prolonging QTc interval",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "currently receiving treatment with any medication which has a relative risk of ... inducing Torsades de Pointes",
                    "criterion": "medication with risk of inducing Torsades de Pointes",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "cannot be switched to an alternative drug or discontinued prior to commencing start of treatment",
                    "criterion": "ability to switch or discontinue medication",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Obligate use of a cardiac pacemaker",
            "criterions": [
                {
                    "exact_snippets": "Obligate use of a cardiac pacemaker",
                    "criterion": "cardiac pacemaker",
                    "requirements": [
                        {
                            "requirement_type": "use",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with a serious active infection at the time of registration or other serious underlying medical conditions that would impair the ability of the patient to receive protocol treatment.",
            "criterions": [
                {
                    "exact_snippets": "serious active infection at the time of registration",
                    "criterion": "serious active infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "serious underlying medical conditions that would impair the ability of the patient to receive protocol treatment",
                    "criterion": "serious underlying medical conditions",
                    "requirements": [
                        {
                            "requirement_type": "impact on treatment ability",
                            "expected_value": "impair the ability to receive protocol treatment"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with a known central nervous system metastases. CT scan of the brain is NOT required unless there is suspicion of CNS metastases.",
            "criterions": [
                {
                    "exact_snippets": "known central nervous system metastases",
                    "criterion": "central nervous system metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "CT scan of the brain is NOT required unless there is suspicion of CNS metastases",
                    "criterion": "CT scan of the brain",
                    "requirements": [
                        {
                            "requirement_type": "requirement",
                            "expected_value": "not required unless suspicion of CNS metastases"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol.",
            "criterions": [
                {
                    "exact_snippets": "Patients with any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol.",
                    "criterion": "condition affecting protocol compliance",
                    "requirements": [
                        {
                            "requirement_type": "compliance",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Pregnant or lactating females.",
            "criterions": [
                {
                    "exact_snippets": "Pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "lactating",
                    "criterion": "lactation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Women of child bearing potential or sexually active males who are not employing adequate contraception. Adequate methods of contraception include use of oral contraceptives or Depot-Provera, with an additional barrier method (diaphragm with spermicidal gel OR condoms with spermicide); a double-barrier method (diaphragm with spermicidal gel AND condoms with spermicide); partner vasectomy and total abstinence.",
            "criterions": [
                {
                    "exact_snippets": "Women of child bearing potential",
                    "criterion": "women of child bearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "sexually active males",
                    "criterion": "sexually active males",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "not employing adequate contraception",
                    "criterion": "adequate contraception",
                    "requirements": [
                        {
                            "requirement_type": "employment",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate methods of contraception include use of oral contraceptives or Depot-Provera, with an additional barrier method (diaphragm with spermicidal gel OR condoms with spermicide); a double-barrier method (diaphragm with spermicidal gel AND condoms with spermicide); partner vasectomy and total abstinence.",
                    "criterion": "adequate contraception methods",
                    "requirements": [
                        {
                            "requirement_type": "methods",
                            "expected_value": [
                                "oral contraceptives",
                                "Depot-Provera",
                                "diaphragm with spermicidal gel OR condoms with spermicide",
                                "diaphragm with spermicidal gel AND condoms with spermicide",
                                "partner vasectomy",
                                "total abstinence"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who received systemic anti-cancer treatment prior to the first dose of study medication within the following time frames:",
            "criterions": [
                {
                    "exact_snippets": "Patients who received systemic anti-cancer treatment prior to the first dose of study medication",
                    "criterion": "prior systemic anti-cancer treatment",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "prior to the first dose of study medication"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Radiotherapy, conventional chemotherapy: within 4 weeks",
            "criterions": [
                {
                    "exact_snippets": "Radiotherapy ... within 4 weeks",
                    "criterion": "radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "conventional chemotherapy: within 4 weeks",
                    "criterion": "conventional chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Palliative radiotherapy: within 2 weeks",
            "criterions": [
                {
                    "exact_snippets": "Palliative radiotherapy: within 2 weeks",
                    "criterion": "palliative radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Monoclonal antibodies: within 4 weeks",
            "criterions": [
                {
                    "exact_snippets": "Monoclonal antibodies: within 4 weeks",
                    "criterion": "monoclonal antibodies",
                    "requirements": [
                        {
                            "requirement_type": "time since last administration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Nitrosoureas and mitomycin: within 6 weeks",
            "criterions": [
                {
                    "exact_snippets": "Nitrosoureas and mitomycin: within 6 weeks",
                    "criterion": "nitrosoureas and mitomycin administration",
                    "requirements": [
                        {
                            "requirement_type": "time since last administration",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Targeted agents or investigational dugs: within 4 weeks",
            "criterions": [
                {
                    "exact_snippets": "Targeted agents or investigational dugs: within 4 weeks",
                    "criterion": "use of targeted agents or investigational drugs",
                    "requirements": [
                        {
                            "requirement_type": "time since last use",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who have had any surgery within 2 weeks prior to registration or who have not recovered from such therapy.",
            "criterions": [
                {
                    "exact_snippets": "Patients who have had any surgery within 2 weeks prior to registration",
                    "criterion": "recent surgery",
                    "requirements": [
                        {
                            "requirement_type": "time since surgery",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "who have not recovered from such therapy",
                    "criterion": "recovery from surgery",
                    "requirements": [
                        {
                            "requirement_type": "recovery status",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients known to be HIV positive. Testing is not required in the absence of clinical signs and symptoms suggestive of HIV infection.",
            "criterions": [
                {
                    "exact_snippets": "Patients known to be HIV positive",
                    "criterion": "HIV status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": "positive"
                        }
                    ]
                },
                {
                    "exact_snippets": "Testing is not required in the absence of clinical signs and symptoms suggestive of HIV infection",
                    "criterion": "clinical signs and symptoms suggestive of HIV infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Treatment with therapeutic doses of coumarin-type anticoagulants. (Maximum daily dose of 2 mg, for line patency permitted)",
            "criterions": [
                {
                    "exact_snippets": "Treatment with therapeutic doses of coumarin-type anticoagulants.",
                    "criterion": "coumarin-type anticoagulants",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Maximum daily dose of 2 mg, for line patency permitted",
                    "criterion": "coumarin-type anticoagulants",
                    "requirements": [
                        {
                            "requirement_type": "maximum daily dose",
                            "expected_value": {
                                "operator": "=",
                                "value": 2,
                                "unit": "mg"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with known disorders due to a deficiency in bilirubin glucuronidation (e.g. Gilbert's syndrome)",
            "criterions": [
                {
                    "exact_snippets": "known disorders due to a deficiency in bilirubin glucuronidation (e.g. Gilbert's syndrome)",
                    "criterion": "disorders due to a deficiency in bilirubin glucuronidation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Unresolved diarrhea ≥ CTCAE grade 2 within 72 hours prior to registration",
            "criterions": [
                {
                    "exact_snippets": "Unresolved diarrhea ≥ CTCAE grade 2 within 72 hours prior to registration",
                    "criterion": "diarrhea",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "CTCAE grade"
                            }
                        },
                        {
                            "requirement_type": "resolution",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 72 hours prior to registration"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with active liver disease that requires intervention.",
            "criterions": [
                {
                    "exact_snippets": "active liver disease",
                    "criterion": "liver disease",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": "active"
                        }
                    ]
                },
                {
                    "exact_snippets": "requires intervention",
                    "criterion": "liver disease",
                    "requirements": [
                        {
                            "requirement_type": "intervention requirement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who cannot give informed consent (i.e. mentally incompetent patients, or those physically incapacitated such as comatose patients). Patients competent but physically unable to sign the consent form may have the document signed by their nearest relative or legal guardian. Each patient will be provided with a full explanation of the study before consent is requested.",
            "criterions": [
                {
                    "exact_snippets": "Patients who cannot give informed consent (i.e. mentally incompetent patients, or those physically incapacitated such as comatose patients)",
                    "criterion": "ability to give informed consent",
                    "requirements": [
                        {
                            "requirement_type": "competence",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "physical capacity",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [
        {
            "line": "* Patients with acute or chronic renal disease. Chronic renal disease will be defined as patients who have stable creatinine ≥ to 1.5 ULN and/or eGFR ≤ 50mL/min. Acute renal disease will be defined as patients that have an acute (within less then 4 weeks) rise in creatinine to ≥ 1.5 ULN and/or eGFR ≤ 50mL/min, that has not resolved to the previously normal baseline levels.",
            "criterions": [
                {
                    "exact_snippets": "acute or chronic renal disease",
                    "criterion": "renal disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "chronic renal disease ... stable creatinine ≥ to 1.5 ULN",
                    "criterion": "chronic renal disease",
                    "requirements": [
                        {
                            "requirement_type": "creatinine level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.5,
                                "unit": "ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "chronic renal disease ... eGFR ≤ 50mL/min",
                    "criterion": "chronic renal disease",
                    "requirements": [
                        {
                            "requirement_type": "eGFR",
                            "expected_value": {
                                "operator": "<=",
                                "value": 50,
                                "unit": "mL/min"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "acute renal disease ... acute (within less then 4 weeks) rise in creatinine to ≥ 1.5 ULN",
                    "criterion": "acute renal disease",
                    "requirements": [
                        {
                            "requirement_type": "creatinine level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.5,
                                "unit": "ULN"
                            }
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within less than 4 weeks"
                        }
                    ]
                },
                {
                    "exact_snippets": "acute renal disease ... eGFR ≤ 50mL/min",
                    "criterion": "acute renal disease",
                    "requirements": [
                        {
                            "requirement_type": "eGFR",
                            "expected_value": {
                                "operator": "<=",
                                "value": 50,
                                "unit": "mL/min"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "acute renal disease ... that has not resolved to the previously normal baseline levels",
                    "criterion": "acute renal disease",
                    "requirements": [
                        {
                            "requirement_type": "resolution",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "failed_miscellaneous": []
}