{
    "info": {
        "nct_id": "NCT02095782",
        "official_title": "Intercalated Combination of Chemotherapy and Erlotinib in 1st Line Setting for Patients Advanced Stage Non-small-cell Lung Cancer With Low Abundant Activating EGFR Mutation(INNOVATE)",
        "inclusion_criteria": "Patients with histologically documented, locally advanced or recurrent (stage IIIb and not amenable to combined modality treatment) or metastatic (stage IV) non-small cell lung cancer.\n\nLow abundant activating EGFR mutation: EGFR exon 19 deletion or exon 21 L858R, which are positive by real-time PCR methods and negative by standard sequencing methods.\n\nUncommon EGFR mutations are included excluding exon 20 mutations. ECOG performance status of ≤ 2. Patients can administer first line setting of platinum based chemotherapy. Patients must have measurable disease according to the RECIST (version 1.1) criteria.\n\n* Life expectancy of at least 12 weeks.\n* Age ≥ 18 years.\n* Written (signed) informed Consent to participate in the study.\n* Adequate organ function as defined by the following criteria:\n\nLiver function: SGOT (AST) and SGPT (ALT) ≤ 2.5 X ULN in the absence of liver metastases or up to 5 X ULN in case of liver metastases. Total bilirubin ≤ 1.5ULN.\n\nBone marrow function: Granulocyte count ≥ 1,500/mm3 and platelet count ≥100,000/mm3 and hemoglobin ≥90g/dl.\n\nRenal function: serum creatinine ≤ 1.5 ULN or creatinine clearance ≥ 60 ml/min. (based on modified Cockcroft-Gault formula).\n\n* For all females of childbearing potential a negative serum/urine pregnancy test must be obtained within 48 hours before enrollment. Postmenopausal women must have been amenorrhoeic for at least 12 months to be considered of non-childbearing potential.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "Patients with prior chemotherapy or systemic anti-cancer therapy including target therapy targeting HER family members (such as erlotinib, gefitinib, cetuximab, trastuzumab, etc). Previous adjuvant or neo-adjuvant treatment for non-metastatic disease is permitted if completed ≥ 6 months before the enrollments.\n\n* Patients with history of any other malignancies within 5 years (except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer).\n* Patients who have brain metastasis or spinal cord compression. It is permitted if the patient has been treated with surgery and/or radiation with evidence of stable disease for at least 4 weeks.\n* Patients who are at risk (in the investigator's opinion) of transmitting human immunodeficiency virus (HIV) through blood or other body fluids.\n* Nursing or lactating women.\n* Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study.\n* Unwilling to write informed consent to participate in the study.\n* Patients who is unwilling to accept the follow-up.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "Patients with histologically documented, locally advanced or recurrent (stage IIIb and not amenable to combined modality treatment) or metastatic (stage IV) non-small cell lung cancer.",
            "criterions": [
                {
                    "exact_snippets": "histologically documented",
                    "criterion": "histological documentation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "locally advanced or recurrent (stage IIIb and not amenable to combined modality treatment)",
                    "criterion": "non-small cell lung cancer stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "IIIb"
                        },
                        {
                            "requirement_type": "treatment amenability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "metastatic (stage IV)",
                    "criterion": "non-small cell lung cancer stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "IV"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Low abundant activating EGFR mutation: EGFR exon 19 deletion or exon 21 L858R, which are positive by real-time PCR methods and negative by standard sequencing methods.",
            "criterions": [
                {
                    "exact_snippets": "Low abundant activating EGFR mutation: EGFR exon 19 deletion or exon 21 L858R",
                    "criterion": "EGFR mutation",
                    "requirements": [
                        {
                            "requirement_type": "mutation type",
                            "expected_value": [
                                "EGFR exon 19 deletion",
                                "exon 21 L858R"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "which are positive by real-time PCR methods",
                    "criterion": "EGFR mutation detection by real-time PCR",
                    "requirements": [
                        {
                            "requirement_type": "detection",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "negative by standard sequencing methods",
                    "criterion": "EGFR mutation detection by standard sequencing",
                    "requirements": [
                        {
                            "requirement_type": "detection",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "Uncommon EGFR mutations are included excluding exon 20 mutations. ECOG performance status of ≤ 2. Patients can administer first line setting of platinum based chemotherapy. Patients must have measurable disease according to the RECIST (version 1.1) criteria.",
            "criterions": [
                {
                    "exact_snippets": "Uncommon EGFR mutations",
                    "criterion": "EGFR mutations",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": "uncommon"
                        }
                    ]
                },
                {
                    "exact_snippets": "excluding exon 20 mutations",
                    "criterion": "EGFR mutations",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": "exon 20 mutations"
                        }
                    ]
                },
                {
                    "exact_snippets": "ECOG performance status of ≤ 2",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients can administer first line setting of platinum based chemotherapy",
                    "criterion": "platinum based chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "administration",
                            "expected_value": "first line setting"
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients must have measurable disease according to the RECIST (version 1.1) criteria",
                    "criterion": "measurable disease",
                    "requirements": [
                        {
                            "requirement_type": "criteria",
                            "expected_value": "RECIST (version 1.1)"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Life expectancy of at least 12 weeks.",
            "criterions": [
                {
                    "exact_snippets": "Life expectancy of at least 12 weeks.",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Age ≥ 18 years.",
            "criterions": [
                {
                    "exact_snippets": "Age ≥ 18 years.",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Written (signed) informed Consent to participate in the study.",
            "criterions": [
                {
                    "exact_snippets": "Written (signed) informed Consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate organ function as defined by the following criteria:",
            "criterions": [
                {
                    "exact_snippets": "Adequate organ function",
                    "criterion": "organ function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Bone marrow function: Granulocyte count ≥ 1,500/mm3 and platelet count ≥100,000/mm3 and hemoglobin ≥90g/dl.",
            "criterions": [
                {
                    "exact_snippets": "Granulocyte count ≥ 1,500/mm3",
                    "criterion": "granulocyte count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1500,
                                "unit": "mm3"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "platelet count ≥100,000/mm3",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100000,
                                "unit": "mm3"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "hemoglobin ≥90g/dl",
                    "criterion": "hemoglobin",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 90,
                                "unit": "g/dl"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Renal function: serum creatinine ≤ 1.5 ULN or creatinine clearance ≥ 60 ml/min. (based on modified Cockcroft-Gault formula).",
            "criterions": [
                {
                    "exact_snippets": "Renal function: serum creatinine ≤ 1.5 ULN",
                    "criterion": "serum creatinine",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Renal function: ... creatinine clearance ≥ 60 ml/min",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "rate",
                            "expected_value": {
                                "operator": ">=",
                                "value": 60,
                                "unit": "ml/min"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* For all females of childbearing potential a negative serum/urine pregnancy test must be obtained within 48 hours before enrollment. Postmenopausal women must have been amenorrhoeic for at least 12 months to be considered of non-childbearing potential.",
            "criterions": [
                {
                    "exact_snippets": "females of childbearing potential",
                    "criterion": "female of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "negative serum/urine pregnancy test",
                    "criterion": "pregnancy test result",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "within 48 hours before enrollment",
                    "criterion": "timing of pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "within 48 hours before enrollment"
                        }
                    ]
                },
                {
                    "exact_snippets": "Postmenopausal women ... amenorrhoeic for at least 12 months",
                    "criterion": "postmenopausal status",
                    "requirements": [
                        {
                            "requirement_type": "amenorrhoeic duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have minimum age of 18 Years",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 18 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "Patients with prior chemotherapy or systemic anti-cancer therapy including target therapy targeting HER family members (such as erlotinib, gefitinib, cetuximab, trastuzumab, etc). Previous adjuvant or neo-adjuvant treatment for non-metastatic disease is permitted if completed ≥ 6 months before the enrollments.",
            "criterions": [
                {
                    "exact_snippets": "prior chemotherapy or systemic anti-cancer therapy",
                    "criterion": "prior chemotherapy or systemic anti-cancer therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "target therapy targeting HER family members (such as erlotinib, gefitinib, cetuximab, trastuzumab, etc)",
                    "criterion": "target therapy targeting HER family members",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Previous adjuvant or neo-adjuvant treatment for non-metastatic disease is permitted if completed ≥ 6 months before the enrollments",
                    "criterion": "adjuvant or neo-adjuvant treatment for non-metastatic disease",
                    "requirements": [
                        {
                            "requirement_type": "completion time",
                            "expected_value": {
                                "operator": ">=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with history of any other malignancies within 5 years (except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer).",
            "criterions": [
                {
                    "exact_snippets": "history of any other malignancies within 5 years",
                    "criterion": "history of other malignancies",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 5,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "adequately treated carcinoma in situ of the cervix",
                    "criterion": "carcinoma in situ of the cervix",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "adequately treated"
                        }
                    ]
                },
                {
                    "exact_snippets": "adequately treated ... basal or squamous cell skin cancer",
                    "criterion": "basal or squamous cell skin cancer",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "adequately treated"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who have brain metastasis or spinal cord compression. It is permitted if the patient has been treated with surgery and/or radiation with evidence of stable disease for at least 4 weeks.",
            "criterions": [
                {
                    "exact_snippets": "brain metastasis",
                    "criterion": "brain metastasis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "spinal cord compression",
                    "criterion": "spinal cord compression",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "treated with surgery and/or radiation",
                    "criterion": "treatment for brain metastasis or spinal cord compression",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": [
                                "surgery",
                                "radiation"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "evidence of stable disease for at least 4 weeks",
                    "criterion": "stable disease",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who are at risk (in the investigator's opinion) of transmitting human immunodeficiency virus (HIV) through blood or other body fluids.",
            "criterions": [
                {
                    "exact_snippets": "at risk (in the investigator's opinion) of transmitting human immunodeficiency virus (HIV)",
                    "criterion": "risk of transmitting HIV",
                    "requirements": [
                        {
                            "requirement_type": "risk assessment",
                            "expected_value": "in the investigator's opinion"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Nursing or lactating women.",
            "criterions": [
                {
                    "exact_snippets": "Nursing or lactating women",
                    "criterion": "nursing or lactating",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study.",
            "criterions": [
                {
                    "exact_snippets": "Sexually active males and females (of childbearing potential)",
                    "criterion": "sexually active status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "females (of childbearing potential)",
                    "criterion": "childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "unwilling to practice contraception during the study",
                    "criterion": "contraception practice",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Unwilling to write informed consent to participate in the study.",
            "criterions": [
                {
                    "exact_snippets": "Unwilling to write informed consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who is unwilling to accept the follow-up.",
            "criterions": [
                {
                    "exact_snippets": "unwilling to accept the follow-up",
                    "criterion": "willingness to accept follow-up",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [
        {
            "line": "Liver function: SGOT (AST) and SGPT (ALT) ≤ 2.5 X ULN in the absence of liver metastases or up to 5 X ULN in case of liver metastases. Total bilirubin ≤ 1.5ULN.",
            "criterions": [
                {
                    "exact_snippets": "Liver function: SGOT (AST) ... ≤ 2.5 X ULN in the absence of liver metastases",
                    "criterion": "SGOT (AST)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "X ULN"
                            }
                        },
                        {
                            "requirement_type": "condition",
                            "expected_value": "absence of liver metastases"
                        }
                    ]
                },
                {
                    "exact_snippets": "Liver function: SGOT (AST) ... up to 5 X ULN in case of liver metastases",
                    "criterion": "SGOT (AST)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 5,
                                "unit": "X ULN"
                            }
                        },
                        {
                            "requirement_type": "condition",
                            "expected_value": "liver metastases"
                        }
                    ]
                },
                {
                    "exact_snippets": "Liver function: SGPT (ALT) ... ≤ 2.5 X ULN in the absence of liver metastases",
                    "criterion": "SGPT (ALT)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "X ULN"
                            }
                        },
                        {
                            "requirement_type": "condition",
                            "expected_value": "absence of liver metastases"
                        }
                    ]
                },
                {
                    "exact_snippets": "Liver function: SGPT (ALT) ... up to 5 X ULN in case of liver metastases",
                    "criterion": "SGPT (ALT)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 5,
                                "unit": "X ULN"
                            }
                        },
                        {
                            "requirement_type": "condition",
                            "expected_value": "liver metastases"
                        }
                    ]
                },
                {
                    "exact_snippets": "Total bilirubin ≤ 1.5ULN",
                    "criterion": "Total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "ULN"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}