{
    "info": {
        "nct_id": "NCT01886573",
        "official_title": "Genome-Wide Methylation and Gene Re-expression Analysis of Resectable Lung Tumor Tissue Pairs Obtained Pre- and Post-Treatment With 5-Azacytidine and Entinostat",
        "inclusion_criteria": "* Undergoing a diagnostic biopsy, including computed tomography (CT)-guided or bronchoscopic for suspected diagnosis of NSCLC\n* Able to understand and sign an informed consent discussing the risks and benefits of obtaining a concurrent research biopsy; patients who have a fresh frozen biopsy available secondary to institutional tissue collection protocols may substitute such a biopsy for the study-required pre-treatment biopsy\n* Histologically confirmed diagnosis of operable NSCLC that has not been previously treated\n* Clinical stage IA-IIIA\n* Appropriate candidate for surgical management, in the opinion of the treating thoracic surgeon\n* Eastern Cooperative Oncology Group (ECOG) performance status =< 2 at the time of initiation of neoadjuvant epigenetic therapy\n* Absolute neutrophil count > 1,000/mcL\n* Platelets > 100,000/mcL\n* Total bilirubin < 1.5 x institutional upper limit of normal (ULN)\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x institutional ULN\n* Creatinine < 1.5 x institutional ULN\n* Able to understand and sign an informed consent\n* Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately\n* Inclusion of women and minorities:\n\n  * Both men and women and members of all races and ethnic groups are eligible for this trial; the coordinating center will be responsible for ensuring each participating site is accruing a representative sample consistent with the estimate of population representation in the site's geographical location for race and ethnic groups as determined by the Census Bureau to assure overall target goals are met\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Patients who have received prior chemotherapy or radiation for their diagnosis of lung cancer\n* Patients may not be receiving any other investigational agent\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to entinostat or 5-azacytidine\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements\n* Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated on this protocol\n* Any co-morbid condition that' in the view of the attending physician' renders the patient at high risk from treatment complications\n* Human immunodeficiency virus (HIV) positive patients on combination antiretroviral therapy are ineligible\n* Known or suspected hypersensitivity to azacitidine or mannitol\n* Patients with advanced malignant hepatic tumors\n* Use of anti-neoplastic or anti-tumor agents that are not part of the study therapy, including chemotherapy, radiation therapy, immunotherapy, and hormonal anticancer therapy, is not permitted while participating in this study; Note: study participants with stage II or III NSCLC, or stage I NSCLC with tumor size greater than 4 cm, should be offered standard adjuvant platinum-based chemotherapy in accordance with local practice (post-operatively)",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Undergoing a diagnostic biopsy, including computed tomography (CT)-guided or bronchoscopic for suspected diagnosis of NSCLC",
            "criterions": [
                {
                    "exact_snippets": "Undergoing a diagnostic biopsy",
                    "criterion": "diagnostic biopsy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "computed tomography (CT)-guided or bronchoscopic",
                    "criterion": "biopsy method",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "computed tomography (CT)-guided",
                                "bronchoscopic"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "suspected diagnosis of NSCLC",
                    "criterion": "suspected diagnosis of NSCLC",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Able to understand and sign an informed consent discussing the risks and benefits of obtaining a concurrent research biopsy; patients who have a fresh frozen biopsy available secondary to institutional tissue collection protocols may substitute such a biopsy for the study-required pre-treatment biopsy",
            "criterions": [
                {
                    "exact_snippets": "Able to understand and sign an informed consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "patients who have a fresh frozen biopsy available",
                    "criterion": "fresh frozen biopsy",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Histologically confirmed diagnosis of operable NSCLC that has not been previously treated",
            "criterions": [
                {
                    "exact_snippets": "Histologically confirmed diagnosis",
                    "criterion": "diagnosis confirmation",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": "histologically"
                        }
                    ]
                },
                {
                    "exact_snippets": "operable NSCLC",
                    "criterion": "NSCLC operability",
                    "requirements": [
                        {
                            "requirement_type": "operability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "NSCLC that has not been previously treated",
                    "criterion": "NSCLC treatment history",
                    "requirements": [
                        {
                            "requirement_type": "treatment history",
                            "expected_value": "not previously treated"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Clinical stage IA-IIIA",
            "criterions": [
                {
                    "exact_snippets": "Clinical stage IA-IIIA",
                    "criterion": "clinical stage",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 1,
                                        "unit": "A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 3,
                                        "unit": "A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Appropriate candidate for surgical management, in the opinion of the treating thoracic surgeon",
            "criterions": [
                {
                    "exact_snippets": "Appropriate candidate for surgical management, in the opinion of the treating thoracic surgeon",
                    "criterion": "surgical management candidacy",
                    "requirements": [
                        {
                            "requirement_type": "opinion",
                            "expected_value": "treating thoracic surgeon"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Eastern Cooperative Oncology Group (ECOG) performance status =< 2 at the time of initiation of neoadjuvant epigenetic therapy",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) performance status =< 2",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "N/A"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Absolute neutrophil count > 1,000/mcL",
            "criterions": [
                {
                    "exact_snippets": "Absolute neutrophil count > 1,000/mcL",
                    "criterion": "absolute neutrophil count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">",
                                "value": 1000,
                                "unit": "mcL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Platelets > 100,000/mcL",
            "criterions": [
                {
                    "exact_snippets": "Platelets > 100,000/mcL",
                    "criterion": "platelets",
                    "requirements": [
                        {
                            "requirement_type": "count",
                            "expected_value": {
                                "operator": ">",
                                "value": 100000,
                                "unit": "mcL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Total bilirubin < 1.5 x institutional upper limit of normal (ULN)",
            "criterions": [
                {
                    "exact_snippets": "Total bilirubin < 1.5 x institutional upper limit of normal (ULN)",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 1.5,
                                "unit": "x institutional upper limit of normal (ULN)"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x institutional ULN",
            "criterions": [
                {
                    "exact_snippets": "Aspartate aminotransferase (AST) ... < 2.5 x institutional ULN",
                    "criterion": "aspartate aminotransferase (AST)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 2.5,
                                "unit": "x institutional ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "alanine aminotransferase (ALT) ... < 2.5 x institutional ULN",
                    "criterion": "alanine aminotransferase (ALT)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 2.5,
                                "unit": "x institutional ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Creatinine < 1.5 x institutional ULN",
            "criterions": [
                {
                    "exact_snippets": "Creatinine < 1.5 x institutional ULN",
                    "criterion": "creatinine level",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<",
                                "value": 1.5,
                                "unit": "x institutional ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Able to understand and sign an informed consent",
            "criterions": [
                {
                    "exact_snippets": "Able to understand",
                    "criterion": "cognitive ability",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": "understand"
                        }
                    ]
                },
                {
                    "exact_snippets": "sign an informed consent",
                    "criterion": "ability to sign informed consent",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately",
            "criterions": [
                {
                    "exact_snippets": "Women of child-bearing potential ... must agree to use adequate contraception",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "men must agree to use adequate contraception",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "should a woman become pregnant ... she should inform her treating physician immediately",
                    "criterion": "pregnancy notification",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Inclusion of women and minorities:",
            "criterions": [
                {
                    "exact_snippets": "Inclusion of women",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "inclusion",
                            "expected_value": "female"
                        }
                    ]
                },
                {
                    "exact_snippets": "Inclusion of ... minorities",
                    "criterion": "ethnicity",
                    "requirements": [
                        {
                            "requirement_type": "inclusion",
                            "expected_value": "minorities"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Both men and women and members of all races and ethnic groups are eligible for this trial; the coordinating center will be responsible for ensuring each participating site is accruing a representative sample consistent with the estimate of population representation in the site's geographical location for race and ethnic groups as determined by the Census Bureau to assure overall target goals are met",
            "criterions": [
                {
                    "exact_snippets": "Both men and women",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "inclusion",
                            "expected_value": [
                                "men",
                                "women"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "members of all races and ethnic groups",
                    "criterion": "race and ethnicity",
                    "requirements": [
                        {
                            "requirement_type": "inclusion",
                            "expected_value": "all races and ethnic groups"
                        }
                    ]
                }
            ]
        },
        {
            "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 who have received prior chemotherapy or radiation for their diagnosis of lung cancer",
            "criterions": [
                {
                    "exact_snippets": "Patients who have received prior chemotherapy",
                    "criterion": "prior chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients who have received prior ... radiation",
                    "criterion": "prior radiation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "diagnosis of lung cancer",
                    "criterion": "lung cancer diagnosis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients may not be receiving any other investigational agent",
            "criterions": [
                {
                    "exact_snippets": "Patients may not be receiving any other investigational agent",
                    "criterion": "investigational agent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of allergic reactions attributed to compounds of similar chemical or biologic composition to entinostat or 5-azacytidine",
            "criterions": [
                {
                    "exact_snippets": "History of allergic reactions attributed to compounds of similar chemical or biologic composition to entinostat or 5-azacytidine",
                    "criterion": "allergic reactions",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "attribution",
                            "expected_value": [
                                "compounds of similar chemical or biologic composition to entinostat",
                                "compounds of similar chemical or biologic composition to 5-azacytidine"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements",
            "criterions": [
                {
                    "exact_snippets": "Uncontrolled intercurrent illness ... ongoing or active infection",
                    "criterion": "ongoing or active infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Uncontrolled intercurrent illness ... symptomatic congestive heart failure",
                    "criterion": "symptomatic congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Uncontrolled intercurrent illness ... unstable angina pectoris",
                    "criterion": "unstable angina pectoris",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Uncontrolled intercurrent illness ... cardiac arrhythmia",
                    "criterion": "cardiac arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Uncontrolled intercurrent illness ... psychiatric illness/social situations that would limit compliance with study requirements",
                    "criterion": "psychiatric illness/social situations",
                    "requirements": [
                        {
                            "requirement_type": "impact on compliance",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated on this protocol",
            "criterions": [
                {
                    "exact_snippets": "Pregnant women are excluded",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "breastfeeding should be discontinued",
                    "criterion": "breastfeeding",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "discontinued"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any co-morbid condition that' in the view of the attending physician' renders the patient at high risk from treatment complications",
            "criterions": [
                {
                    "exact_snippets": "Any co-morbid condition ... renders the patient at high risk from treatment complications",
                    "criterion": "co-morbid condition",
                    "requirements": [
                        {
                            "requirement_type": "risk assessment",
                            "expected_value": "high risk from treatment complications"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Human immunodeficiency virus (HIV) positive patients on combination antiretroviral therapy are ineligible",
            "criterions": [
                {
                    "exact_snippets": "Human immunodeficiency virus (HIV) positive",
                    "criterion": "HIV status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "on combination antiretroviral therapy",
                    "criterion": "combination antiretroviral therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Known or suspected hypersensitivity to azacitidine or mannitol",
            "criterions": [
                {
                    "exact_snippets": "Known or suspected hypersensitivity to azacitidine",
                    "criterion": "hypersensitivity to azacitidine",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Known or suspected hypersensitivity to ... mannitol",
                    "criterion": "hypersensitivity to mannitol",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with advanced malignant hepatic tumors",
            "criterions": [
                {
                    "exact_snippets": "advanced malignant hepatic tumors",
                    "criterion": "hepatic tumors",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "advanced"
                        },
                        {
                            "requirement_type": "malignancy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Use of anti-neoplastic or anti-tumor agents that are not part of the study therapy, including chemotherapy, radiation therapy, immunotherapy, and hormonal anticancer therapy, is not permitted while participating in this study; Note: study participants with stage II or III NSCLC, or stage I NSCLC with tumor size greater than 4 cm, should be offered standard adjuvant platinum-based chemotherapy in accordance with local practice (post-operatively)",
            "criterions": [
                {
                    "exact_snippets": "Use of anti-neoplastic or anti-tumor agents that are not part of the study therapy, including chemotherapy, radiation therapy, immunotherapy, and hormonal anticancer therapy, is not permitted while participating in this study",
                    "criterion": "use of anti-neoplastic or anti-tumor agents",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "study participants with stage II or III NSCLC",
                    "criterion": "NSCLC stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "II",
                                "III"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "stage I NSCLC with tumor size greater than 4 cm",
                    "criterion": "NSCLC stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "I"
                        }
                    ]
                },
                {
                    "exact_snippets": "stage I NSCLC with tumor size greater than 4 cm",
                    "criterion": "tumor size",
                    "requirements": [
                        {
                            "requirement_type": "size",
                            "expected_value": {
                                "operator": ">",
                                "value": 4,
                                "unit": "cm"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}