{
    "info": {
        "nct_id": "NCT01585701",
        "official_title": "A Cancer Research UK Phase I First in Man Study of the Novel AGC Kinase Inhibitor AT13148 Given Orally in Patients With Advanced Solid Tumours.",
        "inclusion_criteria": "1. Histologically proven advanced solid tumours, refractory to conventional treatment, or for which no conventional therapy exists or is declined by the patient. Paraffin-embedded tumour tissue must be available for genetic mutation status testing.\n2. Life expectancy of at least 12 weeks\n3. World Health Organisation (WHO) performance status of 0, 1 or 2\n4. Haematological and biochemical indices within the ranges shown below. These measurements must be performed within 7 days before their first dose of AT13148 taken between Day -7 to -4.\n\n   Laboratory Test Value required\n\n   Haemoglobin (Hb) ≥ 9.0 g/dL\n\n   Absolute neutrophil count ≥ 1.5 x 10^9 /L\n\n   Platelet count ≥ 100 x 10^9/L\n\n   Fasting glucose ≤ 7 mmol/L\n\n   Either:\n\n   Serum bilirubin ≤ 1.5 x upper limit of normal (ULN)\n\n   Or:\n\n   Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x (ULN) unless raised due to tumour in which case up to 5 x ULN is permissible\n\n   Either:\n\n   Calculated creatinine clearance ≥ 50 mL/min\n\n   Or:\n\n   Isotope clearance measurement ≥ 50mL/min (uncorrected)\n5. Adequate lung function indicated by a resting oxygen saturation level (on air) ≥ 94%, a CO-transfer factor > 60%\n6. 18 years or over\n7. Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "1. Radiotherapy (except for palliative reasons), endocrine therapy (except luteinizing hormone releasing hormone (LHRH) agonists for prostate cancer), immunotherapy or chemotherapy during the previous four weeks (six weeks for nitrosoureas, Mitomycin-C) and 4 weeks for investigational medicinal products) before treatment.\n2. Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 1 toxicities, which in the opinion of the Investigator and the Drug Development Office (DDO) should not exclude the patient.\n3. Symptomatic brain metastases (if present they must have been stable for > 3 months).\n4. Ability to become pregnant (or already pregnant or lactating). However, those female patients who have a negative serum or urine pregnancy test before enrolment and agree to use two highly effective forms of contraception (oral, injected or implanted hormonal contraception and condom, have a intra-uterine device and condom, diaphragm with spermicidal gel and condom) during the study and for six months afterwards are considered eligible.\n5. Male patients with partners of child-bearing potential (unless they agree to take measures not to father children by using one form of highly effective contraception [condom plus spermicide] during the study and for six months afterwards). Men with pregnant or lactating partners should be advised to use barrier method contraception (e.g. condom plus spermicidal gel) to prevent exposure to the foetus or neonate.\n6. Major thoracic or abdominal surgery from which the patient has not yet recovered.\n7. At high medical risk because of non-malignant systemic disease including active uncontrolled infection.\n8. Known to be serologically positive for Hepatitis B, Hepatitis C or Human Immunodeficiency Virus (HIV).\n9. History of auto-immune disease or known allergy to peanuts.\n10. Concurrent hypotension defined as a baseline supine blood pressure (BP) systolic < 90 mmHg.\n11. Patients receiving anti-hypertensive treatment or treatment with beta- blockers or rate-limiting calcium agents. A washout period of 5 x half- life of the drug should be applied following withdrawal of any of these treatments.\n12. Concurrent congestive heart failure, prior history of class III/ IV cardiac disease (New York Heart Association [NYHA]), prior history of cardiac ischaemia or prior history of cardiac arrhythmia. Coronary angioplasty or stenting in the previous 12 months.\n13. Patients with a known left ventricular ejection fraction (LVEF) < 50%. A multi-gated acquisition (MUGA) scan or echocardiogram (ECHO) must be performed in all patients.\n14. Concurrent diabetes requiring treatment (diet-controlled diabetes would be acceptable).\n15. Prior bone marrow transplant or have had extensive radiotherapy to greater than 25% of bone marrow within eight weeks.\n16. A history of or underlying interstitial lung disease.\n17. Any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical study.\n18. Is a participant or plans to participate in another interventional clinical study whilst taking part in this study. Participation in an observational study would be acceptable.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Histologically proven advanced solid tumours, refractory to conventional treatment, or for which no conventional therapy exists or is declined by the patient. Paraffin-embedded tumour tissue must be available for genetic mutation status testing.",
            "criterions": [
                {
                    "exact_snippets": "Histologically proven advanced solid tumours",
                    "criterion": "advanced solid tumours",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": "histologically proven"
                        }
                    ]
                },
                {
                    "exact_snippets": "refractory to conventional treatment",
                    "criterion": "refractory to conventional treatment",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "no conventional therapy exists",
                    "criterion": "conventional therapy",
                    "requirements": [
                        {
                            "requirement_type": "existence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "is declined by the patient",
                    "criterion": "conventional therapy",
                    "requirements": [
                        {
                            "requirement_type": "acceptance",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Paraffin-embedded tumour tissue must be available",
                    "criterion": "paraffin-embedded tumour tissue",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "genetic mutation status testing",
                    "criterion": "genetic mutation status testing",
                    "requirements": [
                        {
                            "requirement_type": "requirement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Life expectancy of at least 12 weeks",
            "criterions": [
                {
                    "exact_snippets": "Life expectancy of at least 12 weeks",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. World Health Organisation (WHO) performance status of 0, 1 or 2",
            "criterions": [
                {
                    "exact_snippets": "World Health Organisation (WHO) performance status of 0, 1 or 2",
                    "criterion": "WHO performance status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": [
                                "0",
                                "1",
                                "2"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Haematological and biochemical indices within the ranges shown below. These measurements must be performed within 7 days before their first dose of AT13148 taken between Day -7 to -4.",
            "criterions": [
                {
                    "exact_snippets": "Haematological and biochemical indices within the ranges shown below",
                    "criterion": "haematological and biochemical indices",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": "within the ranges shown below"
                        }
                    ]
                },
                {
                    "exact_snippets": "These measurements must be performed within 7 days before their first dose of AT13148",
                    "criterion": "timing of measurements",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "within 7 days before first dose of AT13148"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Laboratory Test Value required",
            "criterions": [
                {
                    "exact_snippets": "Laboratory Test Value required",
                    "criterion": "laboratory test value",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Haemoglobin (Hb) ≥ 9.0 g/dL",
            "criterions": [
                {
                    "exact_snippets": "Haemoglobin (Hb) ≥ 9.0 g/dL",
                    "criterion": "haemoglobin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 9.0,
                                "unit": "g/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Absolute neutrophil count ≥ 1.5 x 10^9 /L",
            "criterions": [
                {
                    "exact_snippets": "Absolute neutrophil count ≥ 1.5 x 10^9 /L",
                    "criterion": "absolute neutrophil count",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.5,
                                "unit": "x 10^9 /L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Platelet count ≥ 100 x 10^9/L",
            "criterions": [
                {
                    "exact_snippets": "Platelet count ≥ 100 x 10^9/L",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100,
                                "unit": "x 10^9/L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Fasting glucose ≤ 7 mmol/L",
            "criterions": [
                {
                    "exact_snippets": "Fasting glucose ≤ 7 mmol/L",
                    "criterion": "fasting glucose",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 7,
                                "unit": "mmol/L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Serum bilirubin ≤ 1.5 x upper limit of normal (ULN)",
            "criterions": [
                {
                    "exact_snippets": "Serum bilirubin ≤ 1.5 x upper limit of normal (ULN)",
                    "criterion": "serum bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Or:",
            "criterions": [
                {
                    "exact_snippets": "Or",
                    "criterion": "logical operator",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": "or"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x (ULN) unless raised due to tumour in which case up to 5 x ULN is permissible",
            "criterions": [
                {
                    "exact_snippets": "Alanine aminotransferase (ALT) ... ≤ 2.5 x (ULN) unless raised due to tumour in which case up to 5 x ULN is permissible",
                    "criterion": "Alanine aminotransferase (ALT)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 2.5,
                                        "unit": "x ULN"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 5,
                                        "unit": "x ULN"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "condition",
                            "expected_value": "unless raised due to tumour"
                        }
                    ]
                },
                {
                    "exact_snippets": "aspartate aminotransferase (AST) ≤ 2.5 x (ULN) unless raised due to tumour in which case up to 5 x ULN is permissible",
                    "criterion": "aspartate aminotransferase (AST)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 2.5,
                                        "unit": "x ULN"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 5,
                                        "unit": "x ULN"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "condition",
                            "expected_value": "unless raised due to tumour"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Calculated creatinine clearance ≥ 50 mL/min",
            "criterions": [
                {
                    "exact_snippets": "creatinine clearance ≥ 50 mL/min",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 50,
                                "unit": "mL/min"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Or:",
            "criterions": [
                {
                    "exact_snippets": "Or:",
                    "criterion": "alternative criteria",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Isotope clearance measurement ≥ 50mL/min (uncorrected)",
            "criterions": [
                {
                    "exact_snippets": "Isotope clearance measurement ≥ 50mL/min",
                    "criterion": "isotope clearance",
                    "requirements": [
                        {
                            "requirement_type": "measurement",
                            "expected_value": {
                                "operator": ">=",
                                "value": 50,
                                "unit": "mL/min"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Adequate lung function indicated by a resting oxygen saturation level (on air) ≥ 94%, a CO-transfer factor > 60%",
            "criterions": [
                {
                    "exact_snippets": "Adequate lung function indicated by a resting oxygen saturation level (on air) ≥ 94%",
                    "criterion": "resting oxygen saturation level",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": {
                                "operator": ">=",
                                "value": 94,
                                "unit": "%"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate lung function indicated by ... a CO-transfer factor > 60%",
                    "criterion": "CO-transfer factor",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": {
                                "operator": ">",
                                "value": 60,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. 18 years or over",
            "criterions": [
                {
                    "exact_snippets": "18 years or over",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up",
            "criterions": [
                {
                    "exact_snippets": "Written (signed and dated) informed consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "capable of co-operating with treatment and follow-up",
                    "criterion": "capability to cooperate",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have minimum age of 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. Radiotherapy (except for palliative reasons), endocrine therapy (except luteinizing hormone releasing hormone (LHRH) agonists for prostate cancer), immunotherapy or chemotherapy during the previous four weeks (six weeks for nitrosoureas, Mitomycin-C) and 4 weeks for investigational medicinal products) before treatment.",
            "criterions": [
                {
                    "exact_snippets": "Radiotherapy (except for palliative reasons) ... during the previous four weeks",
                    "criterion": "radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "endocrine therapy (except luteinizing hormone releasing hormone (LHRH) agonists for prostate cancer) ... during the previous four weeks",
                    "criterion": "endocrine therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "immunotherapy ... during the previous four weeks",
                    "criterion": "immunotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "chemotherapy during the previous four weeks (six weeks for nitrosoureas, Mitomycin-C)",
                    "criterion": "chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 4,
                                        "unit": "weeks"
                                    },
                                    {
                                        "operator": ">=",
                                        "value": 6,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "4 weeks for investigational medicinal products",
                    "criterion": "investigational medicinal products",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 1 toxicities, which in the opinion of the Investigator and the Drug Development Office (DDO) should not exclude the patient.",
            "criterions": [
                {
                    "exact_snippets": "Ongoing toxic manifestations of previous treatments",
                    "criterion": "toxic manifestations of previous treatments",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "alopecia",
                    "criterion": "alopecia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "certain Grade 1 toxicities",
                    "criterion": "Grade 1 toxicities",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "Grade 1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Symptomatic brain metastases (if present they must have been stable for > 3 months).",
            "criterions": [
                {
                    "exact_snippets": "Symptomatic brain metastases",
                    "criterion": "symptomatic brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "if present they must have been stable for > 3 months",
                    "criterion": "brain metastases stability",
                    "requirements": [
                        {
                            "requirement_type": "stability duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Ability to become pregnant (or already pregnant or lactating). However, those female patients who have a negative serum or urine pregnancy test before enrolment and agree to use two highly effective forms of contraception (oral, injected or implanted hormonal contraception and condom, have a intra-uterine device and condom, diaphragm with spermicidal gel and condom) during the study and for six months afterwards are considered eligible.",
            "criterions": [
                {
                    "exact_snippets": "Ability to become pregnant",
                    "criterion": "ability to become pregnant",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "already pregnant",
                    "criterion": "pregnancy status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "lactating",
                    "criterion": "lactation status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "negative serum or urine pregnancy test before enrolment",
                    "criterion": "pregnancy test result",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "agree to use two highly effective forms of contraception",
                    "criterion": "contraception agreement",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "oral, injected or implanted hormonal contraception and condom",
                    "criterion": "contraception method",
                    "requirements": [
                        {
                            "requirement_type": "methods",
                            "expected_value": [
                                "oral hormonal contraception",
                                "injected hormonal contraception",
                                "implanted hormonal contraception",
                                "condom"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "intra-uterine device and condom",
                    "criterion": "contraception method",
                    "requirements": [
                        {
                            "requirement_type": "methods",
                            "expected_value": [
                                "intra-uterine device",
                                "condom"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "diaphragm with spermicidal gel and condom",
                    "criterion": "contraception method",
                    "requirements": [
                        {
                            "requirement_type": "methods",
                            "expected_value": [
                                "diaphragm with spermicidal gel",
                                "condom"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "during the study and for six months afterwards",
                    "criterion": "contraception duration",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "during the study and for six months afterwards"
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Male patients with partners of child-bearing potential (unless they agree to take measures not to father children by using one form of highly effective contraception [condom plus spermicide] during the study and for six months afterwards). Men with pregnant or lactating partners should be advised to use barrier method contraception (e.g. condom plus spermicidal gel) to prevent exposure to the foetus or neonate.",
            "criterions": [
                {
                    "exact_snippets": "Male patients",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "expected_value",
                            "expected_value": "male"
                        }
                    ]
                },
                {
                    "exact_snippets": "partners of child-bearing potential",
                    "criterion": "partner's child-bearing potential",
                    "requirements": [
                        {
                            "requirement_type": "expected_value",
                            "expected_value": "child-bearing potential"
                        }
                    ]
                },
                {
                    "exact_snippets": "unless they agree to take measures not to father children by using one form of highly effective contraception [condom plus spermicide] during the study and for six months afterwards",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "expected_value",
                            "expected_value": "one form of highly effective contraception [condom plus spermicide] during the study and for six months afterwards"
                        }
                    ]
                },
                {
                    "exact_snippets": "Men with pregnant or lactating partners",
                    "criterion": "partner's pregnancy or lactation status",
                    "requirements": [
                        {
                            "requirement_type": "expected_value",
                            "expected_value": [
                                "pregnant",
                                "lactating"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "should be advised to use barrier method contraception (e.g. condom plus spermicidal gel) to prevent exposure to the foetus or neonate",
                    "criterion": "contraception use with pregnant or lactating partners",
                    "requirements": [
                        {
                            "requirement_type": "expected_value",
                            "expected_value": "barrier method contraception (e.g. condom plus spermicidal gel)"
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Major thoracic or abdominal surgery from which the patient has not yet recovered.",
            "criterions": [
                {
                    "exact_snippets": "Major thoracic or abdominal surgery from which the patient has not yet recovered",
                    "criterion": "recovery from major thoracic or abdominal surgery",
                    "requirements": [
                        {
                            "requirement_type": "recovery status",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. At high medical risk because of non-malignant systemic disease including active uncontrolled infection.",
            "criterions": [
                {
                    "exact_snippets": "high medical risk because of non-malignant systemic disease",
                    "criterion": "non-malignant systemic disease",
                    "requirements": [
                        {
                            "requirement_type": "risk level",
                            "expected_value": "high"
                        }
                    ]
                },
                {
                    "exact_snippets": "active uncontrolled infection",
                    "criterion": "infection",
                    "requirements": [
                        {
                            "requirement_type": "control status",
                            "expected_value": "uncontrolled"
                        },
                        {
                            "requirement_type": "activity status",
                            "expected_value": "active"
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. History of auto-immune disease or known allergy to peanuts.",
            "criterions": [
                {
                    "exact_snippets": "History of auto-immune disease",
                    "criterion": "auto-immune disease",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "known allergy to peanuts",
                    "criterion": "allergy to peanuts",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Concurrent hypotension defined as a baseline supine blood pressure (BP) systolic < 90 mmHg.",
            "criterions": [
                {
                    "exact_snippets": "Concurrent hypotension defined as a baseline supine blood pressure (BP) systolic < 90 mmHg.",
                    "criterion": "systolic blood pressure",
                    "requirements": [
                        {
                            "requirement_type": "measurement",
                            "expected_value": {
                                "operator": "<",
                                "value": 90,
                                "unit": "mmHg"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. Concurrent congestive heart failure, prior history of class III/ IV cardiac disease (New York Heart Association [NYHA]), prior history of cardiac ischaemia or prior history of cardiac arrhythmia. Coronary angioplasty or stenting in the previous 12 months.",
            "criterions": [
                {
                    "exact_snippets": "Concurrent congestive heart failure",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "prior history of class III/ IV cardiac disease (New York Heart Association [NYHA])",
                    "criterion": "class III/IV cardiac disease",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "prior history of cardiac ischaemia",
                    "criterion": "cardiac ischaemia",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "prior history of cardiac arrhythmia",
                    "criterion": "cardiac arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Coronary angioplasty or stenting in the previous 12 months",
                    "criterion": "coronary angioplasty or stenting",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": {
                                "operator": "<=",
                                "value": 12,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. Patients with a known left ventricular ejection fraction (LVEF) < 50%. A multi-gated acquisition (MUGA) scan or echocardiogram (ECHO) must be performed in all patients.",
            "criterions": [
                {
                    "exact_snippets": "known left ventricular ejection fraction (LVEF) < 50%",
                    "criterion": "left ventricular ejection fraction (LVEF)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<",
                                "value": 50,
                                "unit": "%"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "A multi-gated acquisition (MUGA) scan or echocardiogram (ECHO) must be performed",
                    "criterion": "multi-gated acquisition (MUGA) scan or echocardiogram (ECHO)",
                    "requirements": [
                        {
                            "requirement_type": "performance",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "14. Concurrent diabetes requiring treatment (diet-controlled diabetes would be acceptable).",
            "criterions": [
                {
                    "exact_snippets": "Concurrent diabetes requiring treatment",
                    "criterion": "diabetes",
                    "requirements": [
                        {
                            "requirement_type": "concurrency",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "treatment requirement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "diet-controlled diabetes would be acceptable",
                    "criterion": "diet-controlled diabetes",
                    "requirements": [
                        {
                            "requirement_type": "acceptability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "15. Prior bone marrow transplant or have had extensive radiotherapy to greater than 25% of bone marrow within eight weeks.",
            "criterions": [
                {
                    "exact_snippets": "Prior bone marrow transplant",
                    "criterion": "bone marrow transplant",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "extensive radiotherapy to greater than 25% of bone marrow within eight weeks",
                    "criterion": "radiotherapy to bone marrow",
                    "requirements": [
                        {
                            "requirement_type": "extent",
                            "expected_value": {
                                "operator": ">",
                                "value": 25,
                                "unit": "%"
                            }
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within eight weeks"
                        }
                    ]
                }
            ]
        },
        {
            "line": "16. A history of or underlying interstitial lung disease.",
            "criterions": [
                {
                    "exact_snippets": "A history of or underlying interstitial lung disease",
                    "criterion": "interstitial lung disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "17. Any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical study.",
            "criterions": [
                {
                    "exact_snippets": "Any other condition which in the Investigator's opinion would not make the patient a good candidate",
                    "criterion": "other condition",
                    "requirements": [
                        {
                            "requirement_type": "investigator's opinion",
                            "expected_value": "not a good candidate"
                        }
                    ]
                }
            ]
        },
        {
            "line": "18. Is a participant or plans to participate in another interventional clinical study whilst taking part in this study. Participation in an observational study would be acceptable.",
            "criterions": [
                {
                    "exact_snippets": "Is a participant or plans to participate in another interventional clinical study",
                    "criterion": "participation in another interventional clinical study",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [
        {
            "line": "Either:",
            "criterions": [
                {
                    "exact_snippets": "Tissue from tumor must be available",
                    "criterion": "tumor tissue",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "> 2 cm in diameter",
                    "criterion": "tumor tissue",
                    "requirements": [
                        {
                            "requirement_type": "size",
                            "expected_value": {
                                "operator": ">",
                                "value": 2,
                                "unit": "cm"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Either:",
            "criterions": [
                {
                    "exact_snippets": "Tissue from tumor must be available",
                    "criterion": "tumor tissue",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Tissue from tumor ... > 2 cm in diameter.",
                    "criterion": "tumor tissue",
                    "requirements": [
                        {
                            "requirement_type": "size",
                            "expected_value": {
                                "operator": ">",
                                "value": 2,
                                "unit": "cm"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "failed_exclusion": [
        {
            "line": "8. Known to be serologically positive for Hepatitis B, Hepatitis C or Human Immunodeficiency Virus (HIV).",
            "criterions": [
                {
                    "exact_snippets": "serologically positive for Hepatitis B",
                    "criterion": "Hepatitis B",
                    "requirements": [
                        {
                            "requirement_type": "serological status",
                            "expected_value": "positive"
                        }
                    ]
                },
                {
                    "exact_snippets": "serologically positive for Hepatitis C",
                    "criterion": "Hepatitis C",
                    "requirements": [
                        {
                            "requirement_type": "serological status",
                            "expected_value": "positive"
                        }
                    ]
                },
                {
                    "exact_snippets": "serologically positive for ... Human Immunodeficiency Virus (HIV)",
                    "criterion": "Human Immunodeficiency Virus (HIV)",
                    "requirements": [
                        {
                            "requirement_type": "serological status",
                            "expected_value": "positive"
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Patients receiving anti-hypertensive treatment or treatment with beta- blockers or rate-limiting calcium agents. A washout period of 5 x half- life of the drug should be applied following withdrawal of any of these treatments.",
            "criterions": [
                {
                    "exact_snippets": "Patients receiving anti-hypertensive treatment",
                    "criterion": "anti-hypertensive treatment",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "treatment with beta-blockers",
                    "criterion": "beta-blockers",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "treatment with ... rate-limiting calcium agents",
                    "criterion": "rate-limiting calcium agents",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "failed_miscellaneous": []
}