{
    "info": {
        "nct_id": "NCT02450591",
        "official_title": "Pilot Study of Local Therapies for Oligometastatic Non-Small Cell Lung Cancer Harboring Sensitizing EGFR Mutations",
        "inclusion_criteria": "* Newly diagnosed metastatic lung adenocarcinoma (recurrent or de novo) harboring sensitizing EGFR mutations (L858R, exon 19 deletion, G719A, L861Q, S768I, exon 19 insertions) with oligometastatic disease (≤5 discrete lesions of disease irrespective of location, inclusive of the primary lesion):\n* all sites of disease must be amenable to definitive treatment with a local therapy (surgical resection, stereotactic radiosurgery, ablation and conventional radiation therapy) as determined by surgery, interventional radiology and radiation oncology\n* all intrathoracic lymph nodes (including hilar, mediastinal, and supraclavicular nodal disease) are considered 1 discrete lesion.\n* Each brain metastasis is included as a distinct lesion.\n* Patients already started on erlotinib are eligible as long as their sites of disease are determined to be eligible for definitive local therapy by consensus of the principal investigators within 12 weeks of the patient first taking erlotinib.\n* Lung adenocarcinoma histology confirmed at MSKCC.\n* Available archived tissue to perform molecular analysis\n* Patients without available archived tissue can have repeat biopsies to determine EGFR status as per standard clinical care guidelines\n* Age 18 years or older\n* Karnofsky Performance Status ≥ 70%\n* Adequate bone marrow, liver and renal function, as specified below:\n* Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L\n* Hemoglobin ≥ 8 g/dL\n* Platelets ≥ 100 x 109/L\n* Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) (except for patients with documented Gilbert's Syndrome)\n* AST and ALT ≤ 2.5 x ULN or ≤ 5 x ULN if liver metastases are present\n* Serum creatinine ≤ 1.5 x upper limit of normal or creatinine clearance ≥ 60ml/min for patients with creatinine levels above institutional normal.\n* For women of child-bearing potential, negative pregnancy test within 14 days prior to starting treatment\n* Men and women of childbearing age must be willing to use effective contraception while on treatment and for at least 3 months thereafter\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Treatment with erlotinib prior to developing metastatic disease\n* Patients with activating but not sensitizing mutations (exon 20 insertions, EGFR T790M)\n* Malignant pleural effusion or pleural disease\n* Leptomeningeal disease\n* Any site of disease that is not amenable to definitively local therapy including surgery or radiation therapy\n* Women who are breastfeeding or pregnant\n* Concurrent malignancies other than non-melanoma skin cancer that require active ongoing treatment.\n* Any medical co-morbidities that would preclude surgery or radiation therapy",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Newly diagnosed metastatic lung adenocarcinoma (recurrent or de novo) harboring sensitizing EGFR mutations (L858R, exon 19 deletion, G719A, L861Q, S768I, exon 19 insertions) with oligometastatic disease (≤5 discrete lesions of disease irrespective of location, inclusive of the primary lesion):",
            "criterions": [
                {
                    "exact_snippets": "Newly diagnosed metastatic lung adenocarcinoma",
                    "criterion": "metastatic lung adenocarcinoma",
                    "requirements": [
                        {
                            "requirement_type": "diagnosis",
                            "expected_value": "newly diagnosed"
                        }
                    ]
                },
                {
                    "exact_snippets": "harboring sensitizing EGFR mutations (L858R, exon 19 deletion, G719A, L861Q, S768I, exon 19 insertions)",
                    "criterion": "EGFR mutations",
                    "requirements": [
                        {
                            "requirement_type": "mutation type",
                            "expected_value": [
                                "L858R",
                                "exon 19 deletion",
                                "G719A",
                                "L861Q",
                                "S768I",
                                "exon 19 insertions"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "oligometastatic disease (≤5 discrete lesions of disease irrespective of location, inclusive of the primary lesion)",
                    "criterion": "oligometastatic disease",
                    "requirements": [
                        {
                            "requirement_type": "lesion count",
                            "expected_value": {
                                "operator": "<=",
                                "value": 5,
                                "unit": "discrete lesions"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* all sites of disease must be amenable to definitive treatment with a local therapy (surgical resection, stereotactic radiosurgery, ablation and conventional radiation therapy) as determined by surgery, interventional radiology and radiation oncology",
            "criterions": [
                {
                    "exact_snippets": "all sites of disease must be amenable to definitive treatment with a local therapy (surgical resection, stereotactic radiosurgery, ablation and conventional radiation therapy)",
                    "criterion": "sites of disease",
                    "requirements": [
                        {
                            "requirement_type": "treatment amenability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* all intrathoracic lymph nodes (including hilar, mediastinal, and supraclavicular nodal disease) are considered 1 discrete lesion.",
            "criterions": [
                {
                    "exact_snippets": "intrathoracic lymph nodes (including hilar, mediastinal, and supraclavicular nodal disease)",
                    "criterion": "intrathoracic lymph nodes",
                    "requirements": [
                        {
                            "requirement_type": "consideration",
                            "expected_value": "1 discrete lesion"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Each brain metastasis is included as a distinct lesion.",
            "criterions": [
                {
                    "exact_snippets": "Each brain metastasis is included as a distinct lesion.",
                    "criterion": "brain metastasis",
                    "requirements": [
                        {
                            "requirement_type": "inclusion",
                            "expected_value": "distinct lesion"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients already started on erlotinib are eligible as long as their sites of disease are determined to be eligible for definitive local therapy by consensus of the principal investigators within 12 weeks of the patient first taking erlotinib.",
            "criterions": [
                {
                    "exact_snippets": "Patients already started on erlotinib",
                    "criterion": "erlotinib treatment",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "sites of disease are determined to be eligible for definitive local therapy",
                    "criterion": "sites of disease eligibility for definitive local therapy",
                    "requirements": [
                        {
                            "requirement_type": "eligibility",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "within 12 weeks of the patient first taking erlotinib",
                    "criterion": "time since starting erlotinib",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": "<=",
                                "value": 12,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Lung adenocarcinoma histology confirmed at MSKCC.",
            "criterions": [
                {
                    "exact_snippets": "Lung adenocarcinoma histology confirmed",
                    "criterion": "lung adenocarcinoma histology",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "confirmed at MSKCC",
                    "criterion": "confirmation location",
                    "requirements": [
                        {
                            "requirement_type": "location",
                            "expected_value": "MSKCC"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Available archived tissue to perform molecular analysis",
            "criterions": [
                {
                    "exact_snippets": "Available archived tissue to perform molecular analysis",
                    "criterion": "archived tissue",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients without available archived tissue can have repeat biopsies to determine EGFR status as per standard clinical care guidelines",
            "criterions": [
                {
                    "exact_snippets": "available archived tissue",
                    "criterion": "archived tissue",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "EGFR status",
                    "criterion": "EGFR status",
                    "requirements": [
                        {
                            "requirement_type": "determination",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Age 18 years or older",
            "criterions": [
                {
                    "exact_snippets": "Age 18 years or older",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Karnofsky Performance Status ≥ 70%",
            "criterions": [
                {
                    "exact_snippets": "Karnofsky Performance Status ≥ 70%",
                    "criterion": "Karnofsky Performance Status",
                    "requirements": [
                        {
                            "requirement_type": "N/A",
                            "expected_value": {
                                "operator": ">=",
                                "value": 70,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "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 (ANC)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.5,
                                "unit": "x 109/L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Hemoglobin ≥ 8 g/dL",
            "criterions": [
                {
                    "exact_snippets": "Hemoglobin ≥ 8 g/dL",
                    "criterion": "hemoglobin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 8,
                                "unit": "g/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Platelets ≥ 100 x 109/L",
            "criterions": [
                {
                    "exact_snippets": "Platelets ≥ 100 x 109/L",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100,
                                "unit": "x 10^9/L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) (except for patients with documented Gilbert's Syndrome)",
            "criterions": [
                {
                    "exact_snippets": "Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN)",
                    "criterion": "serum total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "except for patients with documented Gilbert's Syndrome",
                    "criterion": "Gilbert's Syndrome",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* AST and ALT ≤ 2.5 x ULN or ≤ 5 x ULN if liver metastases are present",
            "criterions": [
                {
                    "exact_snippets": "AST and ALT ≤ 2.5 x ULN",
                    "criterion": "AST and ALT levels",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "AST and ALT ... ≤ 5 x ULN if liver metastases are present",
                    "criterion": "AST and ALT levels with liver metastases",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Serum creatinine ≤ 1.5 x upper limit of normal or creatinine clearance ≥ 60ml/min for patients with creatinine levels above institutional normal.",
            "criterions": [
                {
                    "exact_snippets": "Serum creatinine ≤ 1.5 x upper limit of normal",
                    "criterion": "serum creatinine",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x upper limit of normal"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "creatinine clearance ≥ 60ml/min for patients with creatinine levels above institutional normal",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 60,
                                "unit": "ml/min"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* For women of child-bearing potential, negative pregnancy test within 14 days prior to starting treatment",
            "criterions": [
                {
                    "exact_snippets": "women of child-bearing potential",
                    "criterion": "gender and reproductive status",
                    "requirements": [
                        {
                            "requirement_type": "expected gender",
                            "expected_value": "female"
                        },
                        {
                            "requirement_type": "reproductive status",
                            "expected_value": "child-bearing potential"
                        }
                    ]
                },
                {
                    "exact_snippets": "negative pregnancy test within 14 days prior to starting treatment",
                    "criterion": "pregnancy test result",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        },
                        {
                            "requirement_type": "timing",
                            "expected_value": "within 14 days prior to starting treatment"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Men and women of childbearing age must be willing to use effective contraception while on treatment and for at least 3 months thereafter",
            "criterions": [
                {
                    "exact_snippets": "Men and women of childbearing age",
                    "criterion": "childbearing age",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "willing to use effective contraception",
                    "criterion": "use of effective contraception",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "while on treatment and for at least 3 months thereafter",
                    "criterion": "duration of contraception use",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "while on treatment and for at least 3 months thereafter"
                        }
                    ]
                }
            ]
        },
        {
            "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": "* Treatment with erlotinib prior to developing metastatic disease",
            "criterions": [
                {
                    "exact_snippets": "Treatment with erlotinib prior to developing metastatic disease",
                    "criterion": "treatment with erlotinib",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "prior to developing metastatic disease"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with activating but not sensitizing mutations (exon 20 insertions, EGFR T790M)",
            "criterions": [
                {
                    "exact_snippets": "activating but not sensitizing mutations",
                    "criterion": "mutations",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "activating",
                                "not sensitizing"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "exon 20 insertions",
                    "criterion": "exon 20 insertions",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "EGFR T790M",
                    "criterion": "EGFR T790M",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Malignant pleural effusion or pleural disease",
            "criterions": [
                {
                    "exact_snippets": "Malignant pleural effusion",
                    "criterion": "malignant pleural effusion",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "pleural disease",
                    "criterion": "pleural disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Leptomeningeal disease",
            "criterions": [
                {
                    "exact_snippets": "Leptomeningeal disease",
                    "criterion": "leptomeningeal disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any site of disease that is not amenable to definitively local therapy including surgery or radiation therapy",
            "criterions": [
                {
                    "exact_snippets": "site of disease that is not amenable to definitively local therapy including surgery or radiation therapy",
                    "criterion": "site of disease",
                    "requirements": [
                        {
                            "requirement_type": "amenability to local therapy",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Women who are breastfeeding or pregnant",
            "criterions": [
                {
                    "exact_snippets": "Women who are ... pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Women who are breastfeeding",
                    "criterion": "breastfeeding",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Concurrent malignancies other than non-melanoma skin cancer that require active ongoing treatment.",
            "criterions": [
                {
                    "exact_snippets": "Concurrent malignancies other than non-melanoma skin cancer that require active ongoing treatment.",
                    "criterion": "concurrent malignancies",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": "other than non-melanoma skin cancer"
                        },
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "require active ongoing treatment"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any medical co-morbidities that would preclude surgery or radiation therapy",
            "criterions": [
                {
                    "exact_snippets": "Any medical co-morbidities that would preclude surgery or radiation therapy",
                    "criterion": "medical co-morbidities",
                    "requirements": [
                        {
                            "requirement_type": "impact on treatment",
                            "expected_value": "preclude surgery or radiation therapy"
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [
        {
            "line": "* Adequate bone marrow, liver and renal function, as specified below:",
            "criterions": [
                {
                    "exact_snippets": "Adequate bone marrow",
                    "criterion": "bone marrow function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate ... liver function",
                    "criterion": "liver function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate ... renal function",
                    "criterion": "renal function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}