{
    "info": {
        "nct_id": "NCT00681876",
        "official_title": "Phase II Study of Avastin Plus Erbitux Plus Irinotecan as 2nd Line Treatment of Locally Advanced or Metastatic Colorectal Cancer in Patients Achieving Disease Progression as Best Response After 1st Line Treatment With FOLFIRI+Avastin or XELIRI+Avastin",
        "inclusion_criteria": "* Histologically confirmed locally advanced or metastatic colorectal cancer.\n* Measurable or evaluable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST)\n* ECOG performance status ≤ 2\n* Age 18 - 72 years\n* Patients with de novo refractory disease (progression of disease as best response at 1st line therapy with FOLFOX/Avastin)\n* Adequate liver (Bilirubin ≤ 1.5 UNL, SGOT/SGPT ≤ 4 UNL, ALP ≤ 2.5 UNL),renal (Creatinine ≤ 1.5 UNL) and bone marrow (ANC ≥ 1,500/mm3, PLT ≥100,000/mm3) function\n* Patients must be able to understand the nature of this study\n* Written informed consent\nHealthy volunteers allowed\nMust have minimum age of 18 Years\nMust have maximum age of 72 Years",
        "exclusion_criteria": "* History of serious cardiac disease (unstable angina, congestive heart failure, uncontrolled cardiac arrhythmias).\n* History of myocardial infarction or stroke within 6 months.\n* Clinically significant peripheral vascular disease.\n* History of abdominal fistula, gastrointestinal perforation or intraabdominal abscess within 28 days prior to Day 0.\n* Presence of central nervous system or brain mets.\n* Evidence of bleeding diathesis or coagulopathy.\n* Patients with known hypersensitive reaction to cetuximab\n* Blood pressure > 150/100 mmHg.\n* Pregnant or lactating woman.\n* Life expectancy < 3 months.\n* Previous radiotherapy within the last 4 weeks or > 25% of bone marrow.\n* Metastatic infiltration of the liver >50%.\n* Patients with chronic diarrhea (at least for 3 months) or partial bowel obstruction or total colectomy.\n* Active infection requiring antibiotics on Day 1.\n* Second primary malignancy, except for non-melanoma skin cancer and in situ cervical cancer.\n* Psychiatric illness or social situation that would preclude study compliance.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Histologically confirmed locally advanced or metastatic colorectal cancer.",
            "criterions": [
                {
                    "exact_snippets": "Histologically confirmed",
                    "criterion": "histological confirmation",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "locally advanced or metastatic colorectal cancer",
                    "criterion": "colorectal cancer stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "locally advanced",
                                "metastatic"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Measurable or evaluable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST)",
            "criterions": [
                {
                    "exact_snippets": "Measurable or evaluable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST)",
                    "criterion": "disease",
                    "requirements": [
                        {
                            "requirement_type": "measurability",
                            "expected_value": [
                                "measurable",
                                "evaluable"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* ECOG performance status ≤ 2",
            "criterions": [
                {
                    "exact_snippets": "ECOG performance status ≤ 2",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "N/A"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Age 18 - 72 years",
            "criterions": [
                {
                    "exact_snippets": "Age 18 - 72 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 18,
                                        "unit": "years"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 72,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with de novo refractory disease (progression of disease as best response at 1st line therapy with FOLFOX/Avastin)",
            "criterions": [
                {
                    "exact_snippets": "de novo refractory disease",
                    "criterion": "refractory disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "progression of disease as best response at 1st line therapy with FOLFOX/Avastin",
                    "criterion": "progression of disease at 1st line therapy",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": [
                                "FOLFOX",
                                "Avastin"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate liver (Bilirubin ≤ 1.5 UNL, SGOT/SGPT ≤ 4 UNL, ALP ≤ 2.5 UNL),renal (Creatinine ≤ 1.5 UNL) and bone marrow (ANC ≥ 1,500/mm3, PLT ≥100,000/mm3) function",
            "criterions": [
                {
                    "exact_snippets": "Adequate liver (Bilirubin ≤ 1.5 UNL, SGOT/SGPT ≤ 4 UNL, ALP ≤ 2.5 UNL)",
                    "criterion": "liver function",
                    "requirements": [
                        {
                            "requirement_type": "Bilirubin level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "UNL"
                            }
                        },
                        {
                            "requirement_type": "SGOT/SGPT level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "UNL"
                            }
                        },
                        {
                            "requirement_type": "ALP level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "UNL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "renal (Creatinine ≤ 1.5 UNL)",
                    "criterion": "renal function",
                    "requirements": [
                        {
                            "requirement_type": "Creatinine level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "UNL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "bone marrow (ANC ≥ 1,500/mm3, PLT ≥100,000/mm3)",
                    "criterion": "bone marrow function",
                    "requirements": [
                        {
                            "requirement_type": "ANC",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1500,
                                "unit": "mm3"
                            }
                        },
                        {
                            "requirement_type": "PLT",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100000,
                                "unit": "mm3"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must be able to understand the nature of this study",
            "criterions": [
                {
                    "exact_snippets": "Patients must be able to understand the nature of this study",
                    "criterion": "understanding of the study",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Written informed consent",
            "criterions": [
                {
                    "exact_snippets": "Written informed consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "form",
                            "expected_value": "written"
                        }
                    ]
                }
            ]
        },
        {
            "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"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have maximum age of 72 Years",
            "criterions": [
                {
                    "exact_snippets": "maximum age of 72 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "maximum",
                            "expected_value": {
                                "operator": "<=",
                                "value": 72,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "* History of serious cardiac disease (unstable angina, congestive heart failure, uncontrolled cardiac arrhythmias).",
            "criterions": [
                {
                    "exact_snippets": "History of serious cardiac disease (unstable angina",
                    "criterion": "unstable angina",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "History of serious cardiac disease ... congestive heart failure",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "History of serious cardiac disease ... uncontrolled cardiac arrhythmias",
                    "criterion": "uncontrolled cardiac arrhythmias",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of myocardial infarction or stroke within 6 months.",
            "criterions": [
                {
                    "exact_snippets": "History of myocardial infarction",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 6,
                                        "unit": "months"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "History of ... stroke within 6 months",
                    "criterion": "stroke",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 6,
                                        "unit": "months"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Clinically significant peripheral vascular disease.",
            "criterions": [
                {
                    "exact_snippets": "Clinically significant peripheral vascular disease",
                    "criterion": "peripheral vascular disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "clinically significant"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of abdominal fistula, gastrointestinal perforation or intraabdominal abscess within 28 days prior to Day 0.",
            "criterions": [
                {
                    "exact_snippets": "History of abdominal fistula",
                    "criterion": "abdominal fistula",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 28,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "History of ... gastrointestinal perforation",
                    "criterion": "gastrointestinal perforation",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 28,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "History of ... intraabdominal abscess",
                    "criterion": "intraabdominal abscess",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 28,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Presence of central nervous system or brain mets.",
            "criterions": [
                {
                    "exact_snippets": "Presence of central nervous system or brain mets.",
                    "criterion": "central nervous system or brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Evidence of bleeding diathesis or coagulopathy.",
            "criterions": [
                {
                    "exact_snippets": "Evidence of bleeding diathesis",
                    "criterion": "bleeding diathesis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Evidence of ... coagulopathy",
                    "criterion": "coagulopathy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with known hypersensitive reaction to cetuximab",
            "criterions": [
                {
                    "exact_snippets": "known hypersensitive reaction to cetuximab",
                    "criterion": "hypersensitive reaction to cetuximab",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Blood pressure > 150/100 mmHg.",
            "criterions": [
                {
                    "exact_snippets": "Blood pressure > 150/100 mmHg",
                    "criterion": "blood pressure",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">",
                                "value": 150,
                                "unit": "mmHg"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Pregnant or lactating woman.",
            "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": "* Life expectancy < 3 months.",
            "criterions": [
                {
                    "exact_snippets": "Life expectancy < 3 months",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": "<",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Previous radiotherapy within the last 4 weeks or > 25% of bone marrow.",
            "criterions": [
                {
                    "exact_snippets": "Previous radiotherapy within the last 4 weeks",
                    "criterion": "previous radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "> 25% of bone marrow",
                    "criterion": "radiotherapy to bone marrow",
                    "requirements": [
                        {
                            "requirement_type": "extent of treatment",
                            "expected_value": {
                                "operator": ">",
                                "value": 25,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Metastatic infiltration of the liver >50%.",
            "criterions": [
                {
                    "exact_snippets": "Metastatic infiltration of the liver >50%",
                    "criterion": "metastatic infiltration of the liver",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">",
                                "value": 50,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with chronic diarrhea (at least for 3 months) or partial bowel obstruction or total colectomy.",
            "criterions": [
                {
                    "exact_snippets": "chronic diarrhea (at least for 3 months)",
                    "criterion": "chronic diarrhea",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "partial bowel obstruction",
                    "criterion": "partial bowel obstruction",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "total colectomy",
                    "criterion": "total colectomy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Active infection requiring antibiotics on Day 1.",
            "criterions": [
                {
                    "exact_snippets": "Active infection requiring antibiotics on Day 1.",
                    "criterion": "active infection",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": "antibiotics"
                        },
                        {
                            "requirement_type": "timing",
                            "expected_value": "Day 1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Second primary malignancy, except for non-melanoma skin cancer and in situ cervical cancer.",
            "criterions": [
                {
                    "exact_snippets": "Second primary malignancy",
                    "criterion": "second primary malignancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "except for non-melanoma skin cancer",
                    "criterion": "non-melanoma skin cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "except for ... in situ cervical cancer",
                    "criterion": "in situ cervical cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Psychiatric illness or social situation that would preclude study compliance.",
            "criterions": [
                {
                    "exact_snippets": "Psychiatric illness",
                    "criterion": "psychiatric illness",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "social situation that would preclude study compliance",
                    "criterion": "social situation",
                    "requirements": [
                        {
                            "requirement_type": "impact on study compliance",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}