{
    "info": {
        "nct_id": "NCT02641873",
        "official_title": "A Phase I Study of BBI608 Administered With FOLFIRI + Bevacizumab in Adult Patients With Metastatic Colorectal Cancer",
        "inclusion_criteria": "1. A histologically confirmed advanced unresectable, metastatic or recurrent colorectal carcinoma\n2. Evaluable patient by RECISTversion 1.1\n3. Stage IV\n4. ≥ 20 years of age\n5. Life expectancy ≥ 3 months.\n6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1\n7. Patients with following organ function within 14 days before enrollment (on the basis of the most recent data during the period if multiple data are available)\n\n   * Hemoglobin (Hg) ≥ 9.0 g/dL\n   * Neutrophil count ≥ 1.5 x 103/μL\n   * Platelet count ≥ 10 x 104/μL\n   * Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × institutional upper limit of normal (ULN) [≤ 5 × ULN in presence of liver metastases ]\n   * Total bilirubin ≤ 1.5 × institutional ULN [≤ 2 × ULN in presence of liver metastases ]\n   * Creatinine ≤ 1.5 × institutional ULN\n   * Proteinuria by dipstick urine analysis ≤ 1+. [ UPCR (Urine Albumin-to-Creatinine Ratio) ≤ 1, or protein volume of 24-hour urine collection ≤ 1 g, in the case of patients with a 2+ urine dipstick reading]\n8. For female patient of child producing potential: Must agree to use contraception or take measures to avoid pregnancy during the study and for 30 days after the last protocol treatment dose or 6 months after Bevacizumab treatment.. For male patient of child producing potential: Must agree to use contraception or take measures to avoid pregnancy during the study and for 90 days after the last protocol treatment dose or 6 months after Bevacizumab treatment\n9. Females of childbearing potential have a negative urine pregnancy test\n10. Patients who have provided written voluntary consent in person to participate in this study after fully receiving and understanding the information about this study, including study\nHealthy volunteers allowed\nMust have minimum age of 20 Years",
        "exclusion_criteria": "1. Anti-cancer chemotherapy, radiotherapy, immunotherapy, or hormone therapy, or heart therapy within 21 days of the first dose of BBI608\n2. Major surgery within 28 days prior to first dose\n3. Have had a brain metastases with a symptom or requiring treatment\n4. Have had coinstantaneously active multiple primary cancer\n5. Have had a carcinomatous pleural effusion, ascites, or cardiac effusion requiring treatment\n6. Crohn's disease, ulcerative colitis, small intestine resection, diarrhea (watery diarrhea), paralysis intestinal, Intestinal obstruction\n7. Gastrointestinal perforation, tracheo-oesophageal fistula, fistula\n8. Unable or unwilling to swallow BBI608 capsules\n9. Uncontrolled inter-current illness (such as Grade 3 active infection, or serious respiratory disease)\n10. Uncontrolled hypertension\n11. Patients with recent history of hemoptysis of more than 2.5 mL of red blood within 28days before the enrolment\n12. Abnormal ECGs which are clinically significant within 28 days before enrolment\n13. Patients who are New York Heart Association (NYHA) functional classes III, or IV, or unstable angina\n14. Patients newly expressing angina within three months (90 days) before the enrolment\n15. Have had myocardial infarction within six months (180 days)before the enrolment\n16. Administrating with antiarrhythmic drug\n17. Patients who are planning to breast-feeding by whichever 30 days after the last administration of BBI608 or by 6 months after the last administration of Bevacizumab\n18. Patients of pregnancy or possibility of pregnancy at current time or possibility of pregnancy within 6 months after the last administration of Bevacizumab\n19. Have received other investigational products or not finished the assessment in any clinical study within 28 days before enrollment\n20. Known severe hypersensitivity to 5-FU/ levofolinate/ irinotecan/Bevacizumab\n21. Administration of atazanavir sulfate\n22. Prior treatment with BBI608\n23. Ineligible for participation in the study in the opinion of the Investigators",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. A histologically confirmed advanced unresectable, metastatic or recurrent colorectal carcinoma",
            "criterions": [
                {
                    "exact_snippets": "histologically confirmed",
                    "criterion": "histological confirmation",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "advanced unresectable, metastatic or recurrent colorectal carcinoma",
                    "criterion": "colorectal carcinoma",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "advanced",
                                "unresectable",
                                "metastatic",
                                "recurrent"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Evaluable patient by RECISTversion 1.1",
            "criterions": [
                {
                    "exact_snippets": "Evaluable patient by RECISTversion 1.1",
                    "criterion": "evaluable patient",
                    "requirements": [
                        {
                            "requirement_type": "evaluation criteria",
                            "expected_value": "RECIST version 1.1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Stage IV",
            "criterions": [
                {
                    "exact_snippets": "Stage IV",
                    "criterion": "cancer stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "IV"
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. ≥ 20 years of age",
            "criterions": [
                {
                    "exact_snippets": "≥ 20 years of age",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 20,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. 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": "6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1",
                    "criterion": "ECOG Performance Status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": [
                                "0",
                                "1"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Patients with following organ function within 14 days before enrollment (on the basis of the most recent data during the period if multiple data are available)",
            "criterions": [
                {
                    "exact_snippets": "organ function within 14 days before enrollment",
                    "criterion": "organ function",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 14 days before enrollment"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Hemoglobin (Hg) ≥ 9.0 g/dL",
            "criterions": [
                {
                    "exact_snippets": "Hemoglobin (Hg) ≥ 9.0 g/dL",
                    "criterion": "hemoglobin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 9.0,
                                "unit": "g/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Neutrophil count ≥ 1.5 x 103/μL",
            "criterions": [
                {
                    "exact_snippets": "Neutrophil count ≥ 1.5 x 103/μL",
                    "criterion": "neutrophil count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.5,
                                "unit": "x 103/μL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Platelet count ≥ 10 x 104/μL",
            "criterions": [
                {
                    "exact_snippets": "Platelet count ≥ 10 x 104/μL",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 10,
                                "unit": "x 104/μL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × institutional upper limit of normal (ULN) [≤ 5 × ULN in presence of liver metastases ]",
            "criterions": [
                {
                    "exact_snippets": "Aspartate transaminase (AST) ... ≤ 2.5 × institutional upper limit of normal (ULN) [≤ 5 × ULN in presence of liver metastases ]",
                    "criterion": "Aspartate transaminase (AST)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 2.5,
                                        "unit": "× ULN"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "level in presence of liver metastases",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 5,
                                        "unit": "× ULN"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "alanine transaminase (ALT) ≤ 2.5 × institutional upper limit of normal (ULN) [≤ 5 × ULN in presence of liver metastases ]",
                    "criterion": "alanine transaminase (ALT)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 2.5,
                                        "unit": "× ULN"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "level in presence of liver metastases",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 5,
                                        "unit": "× ULN"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Total bilirubin ≤ 1.5 × institutional ULN [≤ 2 × ULN in presence of liver metastases ]",
            "criterions": [
                {
                    "exact_snippets": "Total bilirubin ≤ 1.5 × institutional ULN",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "institutional ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "≤ 2 × ULN in presence of liver metastases",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "ULN"
                            }
                        },
                        {
                            "requirement_type": "condition",
                            "expected_value": "presence of liver metastases"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Creatinine ≤ 1.5 × institutional ULN",
            "criterions": [
                {
                    "exact_snippets": "Creatinine ≤ 1.5 × institutional ULN",
                    "criterion": "creatinine level",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "institutional ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Proteinuria by dipstick urine analysis ≤ 1+. [ UPCR (Urine Albumin-to-Creatinine Ratio) ≤ 1, or protein volume of 24-hour urine collection ≤ 1 g, in the case of patients with a 2+ urine dipstick reading]",
            "criterions": [
                {
                    "exact_snippets": "Proteinuria by dipstick urine analysis ≤ 1+",
                    "criterion": "proteinuria by dipstick urine analysis",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "+"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "UPCR (Urine Albumin-to-Creatinine Ratio) ≤ 1",
                    "criterion": "UPCR (Urine Albumin-to-Creatinine Ratio)",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "protein volume of 24-hour urine collection ≤ 1 g",
                    "criterion": "protein volume of 24-hour urine collection",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "g"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. For female patient of child producing potential: Must agree to use contraception or take measures to avoid pregnancy during the study and for 30 days after the last protocol treatment dose or 6 months after Bevacizumab treatment.. For male patient of child producing potential: Must agree to use contraception or take measures to avoid pregnancy during the study and for 90 days after the last protocol treatment dose or 6 months after Bevacizumab treatment",
            "criterions": [
                {
                    "exact_snippets": "female patient of child producing potential",
                    "criterion": "female patient of child producing potential",
                    "requirements": [
                        {
                            "requirement_type": "agreement to use contraception",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "male patient of child producing potential",
                    "criterion": "male patient of child producing potential",
                    "requirements": [
                        {
                            "requirement_type": "agreement to use contraception",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Females of childbearing potential have a negative urine pregnancy test",
            "criterions": [
                {
                    "exact_snippets": "Females of childbearing potential",
                    "criterion": "females of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "negative urine pregnancy test",
                    "criterion": "urine pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Patients who have provided written voluntary consent in person to participate in this study after fully receiving and understanding the information about this study, including study",
            "criterions": [
                {
                    "exact_snippets": "Patients who have provided written voluntary consent",
                    "criterion": "consent",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": "written"
                        },
                        {
                            "requirement_type": "voluntariness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "after fully receiving and understanding the information about this study",
                    "criterion": "understanding of study information",
                    "requirements": [
                        {
                            "requirement_type": "comprehension",
                            "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 20 Years",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 20 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 20,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "1. Anti-cancer chemotherapy, radiotherapy, immunotherapy, or hormone therapy, or heart therapy within 21 days of the first dose of BBI608",
            "criterions": [
                {
                    "exact_snippets": "Anti-cancer chemotherapy ... within 21 days of the first dose of BBI608",
                    "criterion": "anti-cancer chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 21,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "radiotherapy ... within 21 days of the first dose of BBI608",
                    "criterion": "radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 21,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "immunotherapy ... within 21 days of the first dose of BBI608",
                    "criterion": "immunotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 21,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "hormone therapy ... within 21 days of the first dose of BBI608",
                    "criterion": "hormone therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 21,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "heart therapy within 21 days of the first dose of BBI608",
                    "criterion": "heart therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": "<=",
                                "value": 21,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Major surgery within 28 days prior to first dose",
            "criterions": [
                {
                    "exact_snippets": "Major surgery within 28 days prior to first dose",
                    "criterion": "major surgery",
                    "requirements": [
                        {
                            "requirement_type": "time since",
                            "expected_value": {
                                "operator": "<=",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Have had a brain metastases with a symptom or requiring treatment",
            "criterions": [
                {
                    "exact_snippets": "brain metastases",
                    "criterion": "brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "symptom",
                    "criterion": "symptom",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "requiring treatment",
                    "criterion": "treatment",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Have had coinstantaneously active multiple primary cancer",
            "criterions": [
                {
                    "exact_snippets": "Have had coinstantaneously active multiple primary cancer",
                    "criterion": "multiple primary cancer",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": "coinstantaneously active"
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Have had a carcinomatous pleural effusion, ascites, or cardiac effusion requiring treatment",
            "criterions": [
                {
                    "exact_snippets": "carcinomatous pleural effusion",
                    "criterion": "carcinomatous pleural effusion",
                    "requirements": [
                        {
                            "requirement_type": "treatment requirement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "ascites",
                    "criterion": "ascites",
                    "requirements": [
                        {
                            "requirement_type": "treatment requirement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "cardiac effusion",
                    "criterion": "cardiac effusion",
                    "requirements": [
                        {
                            "requirement_type": "treatment requirement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Crohn's disease, ulcerative colitis, small intestine resection, diarrhea (watery diarrhea), paralysis intestinal, Intestinal obstruction",
            "criterions": [
                {
                    "exact_snippets": "Crohn's disease",
                    "criterion": "Crohn's disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "ulcerative colitis",
                    "criterion": "ulcerative colitis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "small intestine resection",
                    "criterion": "small intestine resection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "diarrhea (watery diarrhea)",
                    "criterion": "diarrhea",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "paralysis intestinal",
                    "criterion": "paralysis intestinal",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Intestinal obstruction",
                    "criterion": "intestinal obstruction",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Gastrointestinal perforation, tracheo-oesophageal fistula, fistula",
            "criterions": [
                {
                    "exact_snippets": "Gastrointestinal perforation",
                    "criterion": "gastrointestinal perforation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "tracheo-oesophageal fistula",
                    "criterion": "tracheo-oesophageal fistula",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "fistula",
                    "criterion": "fistula",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Unable or unwilling to swallow BBI608 capsules",
            "criterions": [
                {
                    "exact_snippets": "Unable ... to swallow BBI608 capsules",
                    "criterion": "ability to swallow BBI608 capsules",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "unwilling to swallow BBI608 capsules",
                    "criterion": "willingness to swallow BBI608 capsules",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Uncontrolled inter-current illness (such as Grade 3 active infection, or serious respiratory disease)",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled inter-current illness",
                    "criterion": "inter-current illness",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Grade 3 active infection",
                    "criterion": "active infection",
                    "requirements": [
                        {
                            "requirement_type": "grade",
                            "expected_value": "3"
                        }
                    ]
                },
                {
                    "exact_snippets": "serious respiratory disease",
                    "criterion": "respiratory disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "serious"
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Uncontrolled hypertension",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled hypertension",
                    "criterion": "hypertension",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": "uncontrolled"
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Patients with recent history of hemoptysis of more than 2.5 mL of red blood within 28days before the enrolment",
            "criterions": [
                {
                    "exact_snippets": "recent history of hemoptysis",
                    "criterion": "hemoptysis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "more than 2.5 mL of red blood",
                    "criterion": "hemoptysis volume",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">",
                                "value": 2.5,
                                "unit": "mL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "within 28days before the enrolment",
                    "criterion": "hemoptysis timing",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 28 days before enrolment"
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. Abnormal ECGs which are clinically significant within 28 days before enrolment",
            "criterions": [
                {
                    "exact_snippets": "Abnormal ECGs which are clinically significant",
                    "criterion": "ECG",
                    "requirements": [
                        {
                            "requirement_type": "abnormality",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "clinical significance",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. Patients who are New York Heart Association (NYHA) functional classes III, or IV, or unstable angina",
            "criterions": [
                {
                    "exact_snippets": "New York Heart Association (NYHA) functional classes III, or IV",
                    "criterion": "NYHA functional class",
                    "requirements": [
                        {
                            "requirement_type": "class",
                            "expected_value": [
                                "III",
                                "IV"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "unstable angina",
                    "criterion": "unstable angina",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "14. Patients newly expressing angina within three months (90 days) before the enrolment",
            "criterions": [
                {
                    "exact_snippets": "Patients newly expressing angina",
                    "criterion": "angina",
                    "requirements": [
                        {
                            "requirement_type": "onset",
                            "expected_value": "newly expressing"
                        }
                    ]
                },
                {
                    "exact_snippets": "within three months (90 days) before the enrolment",
                    "criterion": "angina",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 90,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "15. Have had myocardial infarction within six months (180 days)before the enrolment",
            "criterions": [
                {
                    "exact_snippets": "myocardial infarction within six months (180 days)",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 180,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "16. Administrating with antiarrhythmic drug",
            "criterions": [
                {
                    "exact_snippets": "Administrating with antiarrhythmic drug",
                    "criterion": "antiarrhythmic drug administration",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "17. Patients who are planning to breast-feeding by whichever 30 days after the last administration of BBI608 or by 6 months after the last administration of Bevacizumab",
            "criterions": [
                {
                    "exact_snippets": "Patients who are planning to breast-feeding",
                    "criterion": "breast-feeding",
                    "requirements": [
                        {
                            "requirement_type": "planning",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "30 days after the last administration of BBI608",
                    "criterion": "time since last administration of BBI608",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": "<=",
                                "value": 30,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "6 months after the last administration of Bevacizumab",
                    "criterion": "time since last administration of Bevacizumab",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "18. Patients of pregnancy or possibility of pregnancy at current time or possibility of pregnancy within 6 months after the last administration of Bevacizumab",
            "criterions": [
                {
                    "exact_snippets": "Patients of pregnancy",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "possibility of pregnancy at current time",
                    "criterion": "possibility of pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "time",
                            "expected_value": "current"
                        }
                    ]
                },
                {
                    "exact_snippets": "possibility of pregnancy within 6 months after the last administration of Bevacizumab",
                    "criterion": "possibility of pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "time",
                            "expected_value": "within 6 months after the last administration of Bevacizumab"
                        }
                    ]
                }
            ]
        },
        {
            "line": "19. Have received other investigational products or not finished the assessment in any clinical study within 28 days before enrollment",
            "criterions": [
                {
                    "exact_snippets": "Have received other investigational products",
                    "criterion": "receipt of investigational products",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "not finished the assessment in any clinical study within 28 days before enrollment",
                    "criterion": "completion of assessment in any clinical study",
                    "requirements": [
                        {
                            "requirement_type": "time since completion",
                            "expected_value": {
                                "operator": ">=",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "20. Known severe hypersensitivity to 5-FU/ levofolinate/ irinotecan/Bevacizumab",
            "criterions": [
                {
                    "exact_snippets": "Known severe hypersensitivity to 5-FU",
                    "criterion": "hypersensitivity to 5-FU",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        }
                    ]
                },
                {
                    "exact_snippets": "Known severe hypersensitivity to ... levofolinate",
                    "criterion": "hypersensitivity to levofolinate",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        }
                    ]
                },
                {
                    "exact_snippets": "Known severe hypersensitivity to ... irinotecan",
                    "criterion": "hypersensitivity to irinotecan",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        }
                    ]
                },
                {
                    "exact_snippets": "Known severe hypersensitivity to ... Bevacizumab",
                    "criterion": "hypersensitivity to Bevacizumab",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        }
                    ]
                }
            ]
        },
        {
            "line": "21. Administration of atazanavir sulfate",
            "criterions": [
                {
                    "exact_snippets": "Administration of atazanavir sulfate",
                    "criterion": "atazanavir sulfate",
                    "requirements": [
                        {
                            "requirement_type": "administration",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "22. Prior treatment with BBI608",
            "criterions": [
                {
                    "exact_snippets": "Prior treatment with BBI608",
                    "criterion": "BBI608 treatment",
                    "requirements": [
                        {
                            "requirement_type": "prior treatment",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "23. Ineligible for participation in the study in the opinion of the Investigators",
            "criterions": [
                {
                    "exact_snippets": "Ineligible for participation in the study in the opinion of the Investigators",
                    "criterion": "eligibility for participation",
                    "requirements": [
                        {
                            "requirement_type": "opinion",
                            "expected_value": "Investigators' discretion"
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}