{
    "info": {
        "nct_id": "NCT02028494",
        "official_title": "Evaluation of Response to Two Schedules of Capecitabine in Patients With Metastatic Breast Cancer",
        "inclusion_criteria": "* 1 Subject Inclusion Criteria\n\n  * Informed consent has been obtained.\n  * Metastatic breast cancer.\n  * Measurable or non-measurable disease per RECIST criteria.\n  * Pathologic confirmation of breast cancer.\n  * No limit to the number of prior chemotherapy regimens permitted for metastatic disease.\n  * At least 3 weeks since prior chemotherapy. Patients should have recovered from all acute toxicity from such therapy (excluding alopecia).\n  * Age ≥18.\n  * ECOG 0-2\n  * Absolute Neutrophil Count (ANC )≥1.0; hemoglobin ≥9, platelets\n\n    ≥75.000\n  * AST, ALT and Alkaline phosphatase <2.5x upper limit of normal (or <5x upper limit of normal in the case of liver metastases). Total bilirubin <1.5x upper limit of normal.\n  * Estimated creatinine clearance >50ml/min.\n  * If female of childbearing potential, pregnancy test is negative and the patient agrees to use an effective method to avoid pregnancy during the study.\nHealthy volunteers allowed\nMust be FEMALE\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* HER2 over-expression and/or amplification as determined by immunohistochemistry (3+) or FISH (>2.0).\n\n  * No prior fluoropyrimidine in the metastatic setting. Adjuvant fluoropyrimidine is permitted if >12 months have elapsed since treatment.\n  * No restriction for prior hormonal therapy.\n  * GI malabsorption syndrome which could impair oral drug absorption.\n  * Concurrent use of warfarin is discouraged as drug interactions may make management of INR more difficult.\n  * Central nervous system metastases are permitted if previously treated or clinically stable for at least 3 months.\n  * Pregnant or nursing patients.\n  * Life expectancy <3 months.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Informed consent has been obtained.",
            "criterions": [
                {
                    "exact_snippets": "Informed consent has been obtained.",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "obtained",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Metastatic breast cancer.",
            "criterions": [
                {
                    "exact_snippets": "Metastatic breast cancer",
                    "criterion": "breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "metastatic"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Measurable or non-measurable disease per RECIST criteria.",
            "criterions": [
                {
                    "exact_snippets": "Measurable or non-measurable disease per RECIST criteria",
                    "criterion": "disease measurability",
                    "requirements": [
                        {
                            "requirement_type": "criteria",
                            "expected_value": [
                                "measurable",
                                "non-measurable"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Pathologic confirmation of breast cancer.",
            "criterions": [
                {
                    "exact_snippets": "Pathologic confirmation of breast cancer",
                    "criterion": "breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": "pathologic"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* No limit to the number of prior chemotherapy regimens permitted for metastatic disease.",
            "criterions": [
                {
                    "exact_snippets": "No limit to the number of prior chemotherapy regimens permitted for metastatic disease.",
                    "criterion": "prior chemotherapy regimens",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": "no limit"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* At least 3 weeks since prior chemotherapy. Patients should have recovered from all acute toxicity from such therapy (excluding alopecia).",
            "criterions": [
                {
                    "exact_snippets": "At least 3 weeks since prior chemotherapy",
                    "criterion": "time since prior chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients should have recovered from all acute toxicity from such therapy (excluding alopecia)",
                    "criterion": "recovery from acute toxicity",
                    "requirements": [
                        {
                            "requirement_type": "recovery",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Age ≥18.",
            "criterions": [
                {
                    "exact_snippets": "Age ≥18",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "N/A",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* ECOG 0-2",
            "criterions": [
                {
                    "exact_snippets": "ECOG 0-2",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Absolute Neutrophil Count (ANC )≥1.0; hemoglobin ≥9, platelets",
            "criterions": [
                {
                    "exact_snippets": "Absolute Neutrophil Count (ANC )≥1.0",
                    "criterion": "Absolute Neutrophil Count (ANC)",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.0,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "hemoglobin ≥9",
                    "criterion": "hemoglobin",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 9,
                                "unit": "N/A"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "≥75.000",
            "criterions": [
                {
                    "exact_snippets": "≥75.000",
                    "criterion": "value",
                    "requirements": [
                        {
                            "requirement_type": "comparison",
                            "expected_value": {
                                "operator": ">=",
                                "value": 75.0,
                                "unit": "N/A"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* AST, ALT and Alkaline phosphatase <2.5x upper limit of normal (or <5x upper limit of normal in the case of liver metastases). Total bilirubin <1.5x upper limit of normal.",
            "criterions": [
                {
                    "exact_snippets": "AST, ALT and Alkaline phosphatase <2.5x upper limit of normal (or <5x upper limit of normal in the case of liver metastases)",
                    "criterion": "AST, ALT and Alkaline phosphatase levels",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<",
                                        "value": 2.5,
                                        "unit": "x upper limit of normal"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "level in the case of liver metastases",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<",
                                        "value": 5,
                                        "unit": "x upper limit of normal"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Total bilirubin <1.5x upper limit of normal",
                    "criterion": "Total bilirubin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<",
                                        "value": 1.5,
                                        "unit": "x upper limit of normal"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Estimated creatinine clearance >50ml/min.",
            "criterions": [
                {
                    "exact_snippets": "Estimated creatinine clearance >50ml/min.",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">",
                                "value": 50,
                                "unit": "ml/min"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* If female of childbearing potential, pregnancy test is negative and the patient agrees to use an effective method to avoid pregnancy during the study.",
            "criterions": [
                {
                    "exact_snippets": "female of childbearing potential",
                    "criterion": "gender and reproductive potential",
                    "requirements": [
                        {
                            "requirement_type": "gender",
                            "expected_value": "female"
                        },
                        {
                            "requirement_type": "reproductive potential",
                            "expected_value": "childbearing potential"
                        }
                    ]
                },
                {
                    "exact_snippets": "pregnancy test is negative",
                    "criterion": "pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "patient agrees to use an effective method to avoid pregnancy during the study",
                    "criterion": "contraception agreement",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": "use an effective method to avoid pregnancy during the study"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must be FEMALE",
            "criterions": [
                {
                    "exact_snippets": "Must be FEMALE",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "expected_value",
                            "expected_value": "female"
                        }
                    ]
                }
            ]
        },
        {
            "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": "* HER2 over-expression and/or amplification as determined by immunohistochemistry (3+) or FISH (>2.0).",
            "criterions": [
                {
                    "exact_snippets": "HER2 over-expression and/or amplification",
                    "criterion": "HER2 status",
                    "requirements": [
                        {
                            "requirement_type": "over-expression",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "amplification",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "immunohistochemistry (3+)",
                    "criterion": "HER2 status",
                    "requirements": [
                        {
                            "requirement_type": "immunohistochemistry score",
                            "expected_value": {
                                "operator": "=",
                                "value": 3,
                                "unit": "+"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "FISH (>2.0)",
                    "criterion": "HER2 status",
                    "requirements": [
                        {
                            "requirement_type": "FISH ratio",
                            "expected_value": {
                                "operator": ">",
                                "value": 2.0,
                                "unit": "N/A"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* No prior fluoropyrimidine in the metastatic setting. Adjuvant fluoropyrimidine is permitted if >12 months have elapsed since treatment.",
            "criterions": [
                {
                    "exact_snippets": "No prior fluoropyrimidine in the metastatic setting.",
                    "criterion": "prior fluoropyrimidine in the metastatic setting",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Adjuvant fluoropyrimidine is permitted if >12 months have elapsed since treatment.",
                    "criterion": "adjuvant fluoropyrimidine",
                    "requirements": [
                        {
                            "requirement_type": "elapsed time since treatment",
                            "expected_value": {
                                "operator": ">",
                                "value": 12,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* No restriction for prior hormonal therapy.",
            "criterions": [
                {
                    "exact_snippets": "No restriction for prior hormonal therapy.",
                    "criterion": "prior hormonal therapy",
                    "requirements": [
                        {
                            "requirement_type": "restriction",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* GI malabsorption syndrome which could impair oral drug absorption.",
            "criterions": [
                {
                    "exact_snippets": "GI malabsorption syndrome which could impair oral drug absorption",
                    "criterion": "GI malabsorption syndrome",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Concurrent use of warfarin is discouraged as drug interactions may make management of INR more difficult.",
            "criterions": [
                {
                    "exact_snippets": "Concurrent use of warfarin is discouraged",
                    "criterion": "warfarin use",
                    "requirements": [
                        {
                            "requirement_type": "concurrent use",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Central nervous system metastases are permitted if previously treated or clinically stable for at least 3 months.",
            "criterions": [
                {
                    "exact_snippets": "Central nervous system metastases are permitted",
                    "criterion": "central nervous system metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "if previously treated",
                    "criterion": "central nervous system metastases",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "previously treated"
                        }
                    ]
                },
                {
                    "exact_snippets": "clinically stable for at least 3 months",
                    "criterion": "central nervous system metastases",
                    "requirements": [
                        {
                            "requirement_type": "clinical stability duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Pregnant or nursing patients.",
            "criterions": [
                {
                    "exact_snippets": "Pregnant",
                    "criterion": "pregnancy status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "nursing patients",
                    "criterion": "nursing status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Life expectancy <3 months.",
            "criterions": [
                {
                    "exact_snippets": "Life expectancy <3 months.",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": "<",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [
        {
            "line": "* 1 Subject Inclusion Criteria",
            "criterions": []
        }
    ],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}