{
    "info": {
        "nct_id": "NCT03477162",
        "official_title": "Metformin Pharmacology in Human Cancers",
        "inclusion_criteria": "* Invasive malignant solid tumor of thoracic origin (e.g., lung, esophageal, thymus, mesothelioma, chest wall, mediastinum, trachea, pleura) with the intent to treat or biopsy by surgery as standard of care. Tumor must be ≥2 centimeters (cm).\n* Patients with multicentric disease are eligible. Samples from all available tumors are requested for research purposes.\n* Patients with Type 2 diabetes mellitus being treated with metformin (any dose) for a clinical indication at the time of study enrollment are eligible, and will continue metformin treatment as clinically indicated during the presurgical study period. Their dose of metformin will NOT be changed.\n* Patients not on metformin at the time of study entry must be willing to take metformin extended release (Glucophage® XR, 750 mg QD for 4 days, then 750 mg BID for 3-6 days) for a total of 7-10 days prior to surgery.\n* Patients do not require a diagnosis of diabetes to be enrolled in the study.\n* All patients must be willing to keep a drug diary indicating the dates and times of metformin administration.\n\nPatients must meet the following clinical laboratory criteria:\n\n* Absolute neutrophil count (ANC) greater than or equal to 1,500/mm3 and platelet count greater than or equal to 75,000/mm3.\n* Total bilirubin less than or equal to 1.5x the upper limit of the normal range (ULN).\n* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 3x ULN.\n* Estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73m2 or estimated creatinine clearance (eCrCL) > 60 mL/min\n* Ability to give informed consent.\n* Patients must be willing to provide 20 milliliters (mL) of blood for research use.\n* Patient must be willing to provide consent for use of archived tissue for research.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* History of diabetes that is currently being treated without metformin.\n* Patients who, at the time of study entry, are not taking metformin for a clinical indication, and who will need a radiographic analysis with an iodinated contrast agent during the metformin study treatment period.\n* This criterion does not apply to patients taking clinically indicated metformin at the time of study entry.\n* History of liver disease as defined with liver function tests (LFTs) above those in the inclusion\n* Known hypersensitivity to metformin.\n* History of reactive hypoglycemia.\n* Active or history of lactic acidosis, metabolic acidosis, or diabetic ketoacidosis.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Invasive malignant solid tumor of thoracic origin (e.g., lung, esophageal, thymus, mesothelioma, chest wall, mediastinum, trachea, pleura) with the intent to treat or biopsy by surgery as standard of care. Tumor must be ≥2 centimeters (cm).",
            "criterions": [
                {
                    "exact_snippets": "Invasive malignant solid tumor of thoracic origin (e.g., lung, esophageal, thymus, mesothelioma, chest wall, mediastinum, trachea, pleura)",
                    "criterion": "tumor origin",
                    "requirements": [
                        {
                            "requirement_type": "origin",
                            "expected_value": [
                                "lung",
                                "esophageal",
                                "thymus",
                                "mesothelioma",
                                "chest wall",
                                "mediastinum",
                                "trachea",
                                "pleura"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Invasive malignant solid tumor ... with the intent to treat or biopsy by surgery as standard of care.",
                    "criterion": "treatment intent",
                    "requirements": [
                        {
                            "requirement_type": "intent",
                            "expected_value": "treat or biopsy by surgery as standard of care"
                        }
                    ]
                },
                {
                    "exact_snippets": "Tumor must be ≥2 centimeters (cm).",
                    "criterion": "tumor size",
                    "requirements": [
                        {
                            "requirement_type": "size",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "cm"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with multicentric disease are eligible. Samples from all available tumors are requested for research purposes.",
            "criterions": [
                {
                    "exact_snippets": "multicentric disease",
                    "criterion": "multicentric disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Samples from all available tumors",
                    "criterion": "tumor samples",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with Type 2 diabetes mellitus being treated with metformin (any dose) for a clinical indication at the time of study enrollment are eligible, and will continue metformin treatment as clinically indicated during the presurgical study period. Their dose of metformin will NOT be changed.",
            "criterions": [
                {
                    "exact_snippets": "Patients with Type 2 diabetes mellitus",
                    "criterion": "Type 2 diabetes mellitus",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "being treated with metformin (any dose)",
                    "criterion": "metformin treatment",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Their dose of metformin will NOT be changed",
                    "criterion": "metformin dose change",
                    "requirements": [
                        {
                            "requirement_type": "change",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients not on metformin at the time of study entry must be willing to take metformin extended release (Glucophage® XR, 750 mg QD for 4 days, then 750 mg BID for 3-6 days) for a total of 7-10 days prior to surgery.",
            "criterions": [
                {
                    "exact_snippets": "Patients not on metformin at the time of study entry",
                    "criterion": "metformin usage",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "must be willing to take metformin extended release (Glucophage® XR, 750 mg QD for 4 days, then 750 mg BID for 3-6 days) for a total of 7-10 days prior to surgery",
                    "criterion": "willingness to take metformin",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients do not require a diagnosis of diabetes to be enrolled in the study.",
            "criterions": [
                {
                    "exact_snippets": "do not require a diagnosis of diabetes",
                    "criterion": "diabetes diagnosis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* All patients must be willing to keep a drug diary indicating the dates and times of metformin administration.",
            "criterions": [
                {
                    "exact_snippets": "willing to keep a drug diary",
                    "criterion": "willingness to keep a drug diary",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "indicating the dates and times of metformin administration",
                    "criterion": "drug diary content",
                    "requirements": [
                        {
                            "requirement_type": "content",
                            "expected_value": "dates and times of metformin administration"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Patients must meet the following clinical laboratory criteria:",
            "criterions": [
                {
                    "exact_snippets": "clinical laboratory criteria",
                    "criterion": "clinical laboratory criteria",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Absolute neutrophil count (ANC) greater than or equal to 1,500/mm3 and platelet count greater than or equal to 75,000/mm3.",
            "criterions": [
                {
                    "exact_snippets": "Absolute neutrophil count (ANC) greater than or equal to 1,500/mm3",
                    "criterion": "absolute neutrophil count (ANC)",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1500,
                                "unit": "mm3"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "platelet count greater than or equal to 75,000/mm3",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 75000,
                                "unit": "mm3"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Total bilirubin less than or equal to 1.5x the upper limit of the normal range (ULN).",
            "criterions": [
                {
                    "exact_snippets": "Total bilirubin less than or equal to 1.5x the upper limit of the normal range (ULN).",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 3x ULN.",
            "criterions": [
                {
                    "exact_snippets": "Alanine aminotransferase (ALT) ... less than or equal to 3x ULN",
                    "criterion": "Alanine aminotransferase (ALT)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "aspartate aminotransferase (AST) less than or equal to 3x ULN",
                    "criterion": "aspartate aminotransferase (AST)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73m2 or estimated creatinine clearance (eCrCL) > 60 mL/min",
            "criterions": [
                {
                    "exact_snippets": "Estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73m2",
                    "criterion": "estimated glomerular filtration rate (eGFR)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">",
                                "value": 60,
                                "unit": "mL/min/1.73m2"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "estimated creatinine clearance (eCrCL) > 60 mL/min",
                    "criterion": "estimated creatinine clearance (eCrCL)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">",
                                "value": 60,
                                "unit": "mL/min"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Ability to give informed consent.",
            "criterions": [
                {
                    "exact_snippets": "Ability to give informed consent.",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must be willing to provide 20 milliliters (mL) of blood for research use.",
            "criterions": [
                {
                    "exact_snippets": "willing to provide 20 milliliters (mL) of blood for research use",
                    "criterion": "blood donation",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "=",
                                "value": 20,
                                "unit": "mL"
                            }
                        },
                        {
                            "requirement_type": "purpose",
                            "expected_value": "research use"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patient must be willing to provide consent for use of archived tissue for research.",
            "criterions": [
                {
                    "exact_snippets": "willing to provide consent for use of archived tissue for research",
                    "criterion": "consent for use of archived tissue",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have minimum age of 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": "* History of diabetes that is currently being treated without metformin.",
            "criterions": [
                {
                    "exact_snippets": "History of diabetes",
                    "criterion": "diabetes",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "currently being treated without metformin",
                    "criterion": "diabetes treatment",
                    "requirements": [
                        {
                            "requirement_type": "medication",
                            "expected_value": "not metformin"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who, at the time of study entry, are not taking metformin for a clinical indication, and who will need a radiographic analysis with an iodinated contrast agent during the metformin study treatment period.",
            "criterions": [
                {
                    "exact_snippets": "not taking metformin for a clinical indication",
                    "criterion": "metformin usage",
                    "requirements": [
                        {
                            "requirement_type": "usage",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "will need a radiographic analysis with an iodinated contrast agent",
                    "criterion": "radiographic analysis with iodinated contrast agent",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* This criterion does not apply to patients taking clinically indicated metformin at the time of study entry.",
            "criterions": [
                {
                    "exact_snippets": "patients taking clinically indicated metformin",
                    "criterion": "metformin usage",
                    "requirements": [
                        {
                            "requirement_type": "indication",
                            "expected_value": "clinically indicated"
                        },
                        {
                            "requirement_type": "timing",
                            "expected_value": "at the time of study entry"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of liver disease as defined with liver function tests (LFTs) above those in the inclusion",
            "criterions": [
                {
                    "exact_snippets": "History of liver disease",
                    "criterion": "liver disease",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "liver function tests (LFTs) above those in the inclusion",
                    "criterion": "liver function tests (LFTs)",
                    "requirements": [
                        {
                            "requirement_type": "comparison",
                            "expected_value": "> inclusion criteria"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Known hypersensitivity to metformin.",
            "criterions": [
                {
                    "exact_snippets": "Known hypersensitivity to metformin.",
                    "criterion": "hypersensitivity to metformin",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of reactive hypoglycemia.",
            "criterions": [
                {
                    "exact_snippets": "History of reactive hypoglycemia",
                    "criterion": "reactive hypoglycemia",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Active or history of lactic acidosis, metabolic acidosis, or diabetic ketoacidosis.",
            "criterions": [
                {
                    "exact_snippets": "Active or history of lactic acidosis",
                    "criterion": "lactic acidosis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Active or history of ... metabolic acidosis",
                    "criterion": "metabolic acidosis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Active or history of ... diabetic ketoacidosis",
                    "criterion": "diabetic ketoacidosis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}