{
    "info": {
        "nct_id": "NCT02384850",
        "official_title": "An Investigator Initiated Phase 1 Trial To Evaluate mFOLFOX6 With Selinexor (KPT-330), An Oral Selective Inhibitor Of Nuclear Export (SINE), In Patients With Metastatic Colorectal Cancer",
        "inclusion_criteria": "1. Patients with histologically confirmed diagnosis of colorectal cancer presenting with unresectable stage IV (UICC) disease (primary tumor may be present)\n2. Patients who are feasible for treatment with FOLFOX (prior adjuvant or palliative treatment is allowed)\n3. ECOG (Eastern Cooperative Oncology Group) Performance status ≤ 1\n4. Life expectancy > 3 months\n5. Age ≥18 years\n6. Haematologic function as follows (5% deviation allowed):\n\n   * Absolute neutrophil count (ANC) ≥ 1.5 x 109/L\n   * platelets ≥ 100 x109/L\n   * hemoglobin ≥ 9 g/dl or 5.59 mmol/l\n7. Adequate liver function as follows (10% deviation allowed)\n\n   * serum alanine transaminase (ALT) ≤ 2.5 x ULN (in case of liver metastases < 5 x ULN)\n   * total bilirubin ≤ 1.5 x ULN (patients with Gilbert's syndrome total bilirubin ≤2.5 x ULN)\n8. Adequate renal function as follows (10% deviation allowed)\n\n   · creatinine ≤ 1.5 x ULN\n9. Signed written informed consent\n10. Women of child-bearing potential must have a negative pregnancy test\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy; 2. Treatment with any systemic anticancer therapy ≤ 3 weeks prior to cycle 1 day 1 3. Uncontrolled active infection (Hepatitis B and C infection are NOT exclusion criteria) and/or known HIV infection; 4. Renal failure requiring haemodialysis or peritoneal dialysis; 5. Patients who are pregnant or breast-feeding; 6. Patients with significantly diseased or obstructed gastrointestinal tract, malabsorption, uncontrolled vomiting or diarrhea resulting in inability to swallow oral medications; 7. Presence of symptomatic Central nervous system (CNS) metastasis 8. Unresolved toxicity from previous anti-cancer therapy or incomplete recovery from surgery, in particular oxaliplatin-induced peripheral neuropathy > grade 1.\n\n9. Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or other thromboembolic event.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Patients with histologically confirmed diagnosis of colorectal cancer presenting with unresectable stage IV (UICC) disease (primary tumor may be present)",
            "criterions": [
                {
                    "exact_snippets": [
                        "histologically confirmed diagnosis of colorectal cancer"
                    ],
                    "criterion": "colorectal cancer",
                    "requirement_type": "diagnosis confirmation",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "unresectable stage IV (UICC) disease"
                    ],
                    "criterion": "disease stage",
                    "requirement_type": "stage",
                    "expected_value": "unresectable stage IV (UICC)"
                },
                {
                    "exact_snippets": [
                        "primary tumor may be present"
                    ],
                    "criterion": "primary tumor",
                    "requirement_type": "presence",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "2. Patients who are feasible for treatment with FOLFOX (prior adjuvant or palliative treatment is allowed)",
            "criterions": [
                {
                    "exact_snippets": [
                        "Patients who are feasible for treatment with FOLFOX"
                    ],
                    "criterion": "FOLFOX treatment",
                    "requirement_type": "feasibility",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "prior adjuvant or palliative treatment is allowed"
                    ],
                    "criterion": "prior treatment",
                    "requirement_type": "type",
                    "expected_value": [
                        "adjuvant",
                        "palliative"
                    ]
                }
            ]
        },
        {
            "line": "3. ECOG (Eastern Cooperative Oncology Group) Performance status ≤ 1",
            "criterions": [
                {
                    "exact_snippets": [
                        "ECOG (Eastern Cooperative Oncology Group) Performance status"
                    ],
                    "criterion": "ECOG Performance status",
                    "requirement_type": "value",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 1
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "4. Life expectancy > 3 months",
            "criterions": [
                {
                    "exact_snippets": [
                        "Life expectancy > 3 months"
                    ],
                    "criterion": "life expectancy",
                    "requirement_type": "duration",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">",
                                "value": 3
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "5. Age ≥18 years",
            "criterions": [
                {
                    "exact_snippets": [
                        "Age ≥18 years"
                    ],
                    "criterion": "age",
                    "requirement_type": "N/A",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 18
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "6. Haematologic function as follows (5% deviation allowed):",
            "criterions": [
                {
                    "exact_snippets": [
                        "Haematologic function"
                    ],
                    "criterion": "haematologic function",
                    "requirement_type": "status",
                    "expected_value": "normal or within 5% deviation"
                }
            ]
        },
        {
            "line": "* Absolute neutrophil count (ANC) ≥ 1.5 x 109/L",
            "criterions": [
                {
                    "exact_snippets": [
                        "Absolute neutrophil count (ANC)",
                        "≥ 1.5 x 109/L"
                    ],
                    "criterion": "absolute neutrophil count",
                    "requirement_type": "quantity",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 1.5
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* platelets ≥ 100 x109/L",
            "criterions": [
                {
                    "exact_snippets": [
                        "platelets ≥ 100 x109/L"
                    ],
                    "criterion": "platelets",
                    "requirement_type": "quantity",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 100
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "7. Adequate liver function as follows (10% deviation allowed)",
            "criterions": [
                {
                    "exact_snippets": [
                        "Adequate liver function"
                    ],
                    "criterion": "liver function",
                    "requirement_type": "adequacy",
                    "expected_value": "adequate"
                }
            ]
        },
        {
            "line": "* serum alanine transaminase (ALT) ≤ 2.5 x ULN (in case of liver metastases < 5 x ULN)",
            "criterions": [
                {
                    "exact_snippets": [
                        "serum alanine transaminase (ALT)",
                        "≤ 2.5 x ULN"
                    ],
                    "criterion": "serum alanine transaminase (ALT)",
                    "requirement_type": "level",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 2.5
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "serum alanine transaminase (ALT)",
                        "liver metastases",
                        "< 5 x ULN"
                    ],
                    "criterion": "serum alanine transaminase (ALT)",
                    "requirement_type": "level with liver metastases",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<",
                                "value": 5
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* total bilirubin ≤ 1.5 x ULN (patients with Gilbert's syndrome total bilirubin ≤2.5 x ULN)",
            "criterions": [
                {
                    "exact_snippets": [
                        "total bilirubin ≤ 1.5 x ULN"
                    ],
                    "criterion": "total bilirubin",
                    "requirement_type": "level",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 1.5
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "patients with Gilbert's syndrome total bilirubin ≤2.5 x ULN"
                    ],
                    "criterion": "total bilirubin",
                    "requirement_type": "level",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 2.5
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "8. Adequate renal function as follows (10% deviation allowed)",
            "criterions": [
                {
                    "exact_snippets": [
                        "Adequate renal function"
                    ],
                    "criterion": "renal function",
                    "requirement_type": "adequacy",
                    "expected_value": "adequate"
                },
                {
                    "exact_snippets": [
                        "10% deviation allowed"
                    ],
                    "criterion": "renal function",
                    "requirement_type": "deviation allowance",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "· creatinine ≤ 1.5 x ULN",
            "criterions": [
                {
                    "exact_snippets": [
                        "creatinine ≤ 1.5 x ULN"
                    ],
                    "criterion": "creatinine",
                    "requirement_type": "level",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 1.5
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "creatinine ≤ 1.5 x ULN"
                    ],
                    "criterion": "creatinine",
                    "requirement_type": "comparison to ULN",
                    "expected_value": "1.5 x ULN"
                }
            ]
        },
        {
            "line": "9. Signed written informed consent",
            "criterions": [
                {
                    "exact_snippets": [
                        "Signed written informed consent"
                    ],
                    "criterion": "informed consent",
                    "requirement_type": "signed",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "10. Women of child-bearing potential must have a negative pregnancy test",
            "criterions": [
                {
                    "exact_snippets": [
                        "Women of child-bearing potential"
                    ],
                    "criterion": "child-bearing potential",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "negative pregnancy test"
                    ],
                    "criterion": "pregnancy test",
                    "requirement_type": "result",
                    "expected_value": "negative"
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": [
                        "Healthy volunteers allowed"
                    ],
                    "criterion": "volunteer health status",
                    "requirement_type": "allowance",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "Must have minimum age of 18 Years",
            "criterions": [
                {
                    "exact_snippets": [
                        "minimum age of 18 Years"
                    ],
                    "criterion": "age",
                    "requirement_type": "minimum",
                    "expected_value": {
                        "operator": ">=",
                        "value": 18
                    }
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy; 2. Treatment with any systemic anticancer therapy ≤ 3 weeks prior to cycle 1 day 1 3. Uncontrolled active infection (Hepatitis B and C infection are NOT exclusion criteria) and/or known HIV infection; 4. Renal failure requiring haemodialysis or peritoneal dialysis; 5. Patients who are pregnant or breast-feeding; 6. Patients with significantly diseased or obstructed gastrointestinal tract, malabsorption, uncontrolled vomiting or diarrhea resulting in inability to swallow oral medications; 7. Presence of symptomatic Central nervous system (CNS) metastasis 8. Unresolved toxicity from previous anti-cancer therapy or incomplete recovery from surgery, in particular oxaliplatin-induced peripheral neuropathy > grade 1.",
            "criterions": [
                {
                    "exact_snippets": [
                        "adequately controlled with appropriate therapy"
                    ],
                    "criterion": "therapy control",
                    "requirement_type": "adequacy",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "compromise the patient's ability to tolerate this therapy"
                    ],
                    "criterion": "therapy tolerance",
                    "requirement_type": "ability",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "Treatment with any systemic anticancer therapy ≤ 3 weeks prior to cycle 1 day 1"
                    ],
                    "criterion": "systemic anticancer therapy",
                    "requirement_type": "treatment timing",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 3
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "Uncontrolled active infection"
                    ],
                    "criterion": "active infection",
                    "requirement_type": "control",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "Hepatitis B and C infection are NOT exclusion criteria"
                    ],
                    "criterion": "Hepatitis B and C infection",
                    "requirement_type": "exclusion",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "known HIV infection"
                    ],
                    "criterion": "HIV infection",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "Renal failure requiring haemodialysis or peritoneal dialysis"
                    ],
                    "criterion": "renal failure",
                    "requirement_type": "dialysis requirement",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "Patients who are pregnant or breast-feeding"
                    ],
                    "criterion": "pregnancy or breast-feeding",
                    "requirement_type": "status",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "significantly diseased or obstructed gastrointestinal tract"
                    ],
                    "criterion": "gastrointestinal tract condition",
                    "requirement_type": "disease or obstruction",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "malabsorption"
                    ],
                    "criterion": "malabsorption",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "uncontrolled vomiting or diarrhea resulting in inability to swallow oral medications"
                    ],
                    "criterion": "vomiting or diarrhea",
                    "requirement_type": "control",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "Presence of symptomatic Central nervous system (CNS) metastasis"
                    ],
                    "criterion": "CNS metastasis",
                    "requirement_type": "symptomatic presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "Unresolved toxicity from previous anti-cancer therapy"
                    ],
                    "criterion": "toxicity from previous anti-cancer therapy",
                    "requirement_type": "resolution",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "incomplete recovery from surgery"
                    ],
                    "criterion": "recovery from surgery",
                    "requirement_type": "completeness",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "oxaliplatin-induced peripheral neuropathy > grade 1"
                    ],
                    "criterion": "oxaliplatin-induced peripheral neuropathy",
                    "requirement_type": "severity",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">",
                                "value": 1
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "9. Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or other thromboembolic event.",
            "criterions": [
                {
                    "exact_snippets": [
                        "myocardial infarction",
                        "within the 12 months prior to study drug administration"
                    ],
                    "criterion": "myocardial infarction",
                    "requirement_type": "time since occurrence",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 12
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "severe/unstable angina",
                        "within the 12 months prior to study drug administration"
                    ],
                    "criterion": "angina",
                    "requirement_type": "severity/stability",
                    "expected_value": "severe/unstable"
                },
                {
                    "exact_snippets": [
                        "coronary/peripheral artery bypass graft",
                        "within the 12 months prior to study drug administration"
                    ],
                    "criterion": "coronary/peripheral artery bypass graft",
                    "requirement_type": "time since procedure",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 12
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "symptomatic congestive heart failure",
                        "within the 12 months prior to study drug administration"
                    ],
                    "criterion": "congestive heart failure",
                    "requirement_type": "symptom presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "cerebrovascular accident",
                        "within the 12 months prior to study drug administration"
                    ],
                    "criterion": "cerebrovascular accident",
                    "requirement_type": "time since occurrence",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 12
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "transient ischemic attack",
                        "within the 12 months prior to study drug administration"
                    ],
                    "criterion": "transient ischemic attack",
                    "requirement_type": "time since occurrence",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 12
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "pulmonary embolism",
                        "within the 12 months prior to study drug administration"
                    ],
                    "criterion": "pulmonary embolism",
                    "requirement_type": "time since occurrence",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 12
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "deep vein thrombosis",
                        "within the 12 months prior to study drug administration"
                    ],
                    "criterion": "deep vein thrombosis",
                    "requirement_type": "time since occurrence",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 12
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "other thromboembolic event",
                        "within the 12 months prior to study drug administration"
                    ],
                    "criterion": "thromboembolic event",
                    "requirement_type": "time since occurrence",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 12
                            }
                        ]
                    }
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [
        {
            "line": "* hemoglobin ≥ 9 g/dl or 5.59 mmol/l",
            "criterions": [
                {
                    "exact_snippets": [
                        "hemoglobin ≥ 9 g/dl"
                    ],
                    "criterion": "hemoglobin",
                    "requirement_type": "level",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 9
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "hemoglobin ≥ 5.59 mmol/l"
                    ],
                    "criterion": "hemoglobin",
                    "requirement_type": "level",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 5.59
                            }
                        ]
                    }
                }
            ]
        }
    ],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}