{
    "info": {
        "nct_id": "NCT00196820",
        "official_title": "A Multicenter Phase II Study to Determine the Efficacy of Capecitabine as First Line Monochemotherapy in Patients With HER2 Negative, Medium-risk, Metastatic Breast Cancer",
        "inclusion_criteria": "1. Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements.\n2. Histologically confirmed carcinoma of the breast.\n3. Negative for HER2-overexpression of the primary and/or metastatic tumour tissue detected by immunohistochemistry (DAKO 0-2) or genamplification detected by FISH.\n4. Locally advanced or metastatic stage of disease not suitable for surgery or radiotherapy alone.\n5. The following previous systemic treatment are eligible:\n\n   adjuvant chemotherapy (except if capecitabine was included) adjuvant endocrine therapy palliative endocrine treatments treatment with bisphosphonates (adjuvant and/or palliative) treatment with immunotherapies (adjuvant and/or palliative)\n6. Patients must have either measurable or nonmeasurable target lesions according to the WHO criteria (see Appendix 5).\n7. At least 4 weeks since radiotherapy, with full recovery. The measurable disease must be completely outside the radiation portal or there must be pathologic proof of progressive disease.\n8. Complete radiology and tumor measurement work up within 4 weeks prior to registration.\n9. Karnofsky performance status evaluation > or = 60%\n10. Age >18 years\n11. WBC > or = 3000 cells/microl, platelet count > or = 100,000 cells/microl.\n12. Bilirubin < or = 2x the upper limit of normal for the institution (ULN); elevation of transaminases and alkaline phosphatase < 2.5x ULN or <5x ULN for patients with liver metastases.\n13. Creatinine < or = 1,25 x upper normal value or creatinin-clearance > 50 ml/min (according to Cockroft Gault).\n14. If of childbearing potential, negative pregnancy test. In addition the patient has to agree to use an effective method to avoid pregnancy for the duration of the study.\n15. Female and male patients\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "1. Known hypersensitivity reaction to the compounds or incorporated substances or known dihydropyrimidine dehydrogenase deficiency.\n2. Concurrent immunotherapy or hormonal therapy (antihormonal, contraceptive and/or replacement therapy). Bisphosphonates may be continued.\n3. Parenchymal brain metastases, unless adequately controlled by surgery and/or radiotherapy with complete resolution of symptoms and discontinuation of all steroids.\n4. Life expectancy of less than 3 months.\n5. Serious intercurrent medical or psychiatric illness that may interfere with the planned treatment (including AIDS and serious active infection).\n6. History of other malignancy within the last 5 years which could affect the diagnosis or assessment of metastatic breast cancer.\n7. Patients with indication for polychemotherapy.\n8. Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry.\n9. Treatment with sorivudine or derivates e.g. brivudin.\n10. Pregnant or nursing women.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements.",
            "criterions": [
                {
                    "exact_snippets": "Written informed consent ... must be obtained and documented",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "expected cooperation of the patients for the treatment and follow-up",
                    "criterion": "patient cooperation",
                    "requirements": [
                        {
                            "requirement_type": "expectation",
                            "expected_value": "cooperation for treatment and follow-up"
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Histologically confirmed carcinoma of the breast.",
            "criterions": [
                {
                    "exact_snippets": "Histologically confirmed carcinoma of the breast",
                    "criterion": "carcinoma of the breast",
                    "requirements": [
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": "histologically confirmed"
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Negative for HER2-overexpression of the primary and/or metastatic tumour tissue detected by immunohistochemistry (DAKO 0-2) or genamplification detected by FISH.",
            "criterions": [
                {
                    "exact_snippets": "Negative for HER2-overexpression of the primary and/or metastatic tumour tissue detected by immunohistochemistry (DAKO 0-2)",
                    "criterion": "HER2-overexpression",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Negative for HER2-overexpression of the primary and/or metastatic tumour tissue ... genamplification detected by FISH",
                    "criterion": "HER2 gene amplification",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Locally advanced or metastatic stage of disease not suitable for surgery or radiotherapy alone.",
            "criterions": [
                {
                    "exact_snippets": "Locally advanced or metastatic stage of disease",
                    "criterion": "stage of disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "locally advanced",
                                "metastatic"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "not suitable for surgery",
                    "criterion": "suitability for surgery",
                    "requirements": [
                        {
                            "requirement_type": "suitability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "not suitable for ... radiotherapy alone",
                    "criterion": "suitability for radiotherapy alone",
                    "requirements": [
                        {
                            "requirement_type": "suitability",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. The following previous systemic treatment are eligible:",
            "criterions": [
                {
                    "exact_snippets": "previous systemic treatment",
                    "criterion": "previous systemic treatment",
                    "requirements": [
                        {
                            "requirement_type": "eligibility",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "adjuvant chemotherapy (except if capecitabine was included) adjuvant endocrine therapy palliative endocrine treatments treatment with bisphosphonates (adjuvant and/or palliative) treatment with immunotherapies (adjuvant and/or palliative)",
            "criterions": [
                {
                    "exact_snippets": "adjuvant chemotherapy (except if capecitabine was included)",
                    "criterion": "adjuvant chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": "capecitabine"
                        }
                    ]
                },
                {
                    "exact_snippets": "adjuvant endocrine therapy",
                    "criterion": "adjuvant endocrine therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "palliative endocrine treatments",
                    "criterion": "palliative endocrine treatments",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "treatment with bisphosphonates (adjuvant and/or palliative)",
                    "criterion": "treatment with bisphosphonates",
                    "requirements": [
                        {
                            "requirement_type": "purpose",
                            "expected_value": [
                                "adjuvant",
                                "palliative"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "treatment with immunotherapies (adjuvant and/or palliative)",
                    "criterion": "treatment with immunotherapies",
                    "requirements": [
                        {
                            "requirement_type": "purpose",
                            "expected_value": [
                                "adjuvant",
                                "palliative"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Patients must have either measurable or nonmeasurable target lesions according to the WHO criteria (see Appendix 5).",
            "criterions": [
                {
                    "exact_snippets": "measurable or nonmeasurable target lesions according to the WHO criteria",
                    "criterion": "target lesions",
                    "requirements": [
                        {
                            "requirement_type": "classification",
                            "expected_value": [
                                "measurable",
                                "nonmeasurable"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. At least 4 weeks since radiotherapy, with full recovery. The measurable disease must be completely outside the radiation portal or there must be pathologic proof of progressive disease.",
            "criterions": [
                {
                    "exact_snippets": "At least 4 weeks since radiotherapy",
                    "criterion": "time since radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "full recovery",
                    "criterion": "recovery from radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "full recovery"
                        }
                    ]
                },
                {
                    "exact_snippets": "measurable disease must be completely outside the radiation portal",
                    "criterion": "measurable disease location",
                    "requirements": [
                        {
                            "requirement_type": "location",
                            "expected_value": "completely outside the radiation portal"
                        }
                    ]
                },
                {
                    "exact_snippets": "pathologic proof of progressive disease",
                    "criterion": "progressive disease",
                    "requirements": [
                        {
                            "requirement_type": "proof",
                            "expected_value": "pathologic proof"
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Complete radiology and tumor measurement work up within 4 weeks prior to registration.",
            "criterions": [
                {
                    "exact_snippets": "Complete radiology and tumor measurement work up",
                    "criterion": "radiology and tumor measurement work up",
                    "requirements": [
                        {
                            "requirement_type": "completion",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "within 4 weeks prior to registration",
                    "criterion": "timeframe for radiology and tumor measurement work up",
                    "requirements": [
                        {
                            "requirement_type": "timeframe",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Karnofsky performance status evaluation > or = 60%",
            "criterions": [
                {
                    "exact_snippets": "Karnofsky performance status evaluation > or = 60%",
                    "criterion": "Karnofsky performance status",
                    "requirements": [
                        {
                            "requirement_type": "evaluation",
                            "expected_value": {
                                "operator": ">=",
                                "value": 60,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Age >18 years",
            "criterions": [
                {
                    "exact_snippets": "Age >18 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. WBC > or = 3000 cells/microl, platelet count > or = 100,000 cells/microl.",
            "criterions": [
                {
                    "exact_snippets": "WBC > or = 3000 cells/microl",
                    "criterion": "WBC",
                    "requirements": [
                        {
                            "requirement_type": "count",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3000,
                                "unit": "cells/microl"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "platelet count > or = 100,000 cells/microl",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "count",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100000,
                                "unit": "cells/microl"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. Bilirubin < or = 2x the upper limit of normal for the institution (ULN); elevation of transaminases and alkaline phosphatase < 2.5x ULN or <5x ULN for patients with liver metastases.",
            "criterions": [
                {
                    "exact_snippets": "Bilirubin < or = 2x the upper limit of normal for the institution (ULN)",
                    "criterion": "bilirubin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "x ULN"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "elevation of transaminases ... < 2.5x ULN",
                    "criterion": "transaminase level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<",
                                        "value": 2.5,
                                        "unit": "x ULN"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "elevation of ... alkaline phosphatase < 2.5x ULN",
                    "criterion": "alkaline phosphatase level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<",
                                        "value": 2.5,
                                        "unit": "x ULN"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "elevation of transaminases and alkaline phosphatase ... <5x ULN for patients with liver metastases",
                    "criterion": "transaminase and alkaline phosphatase level in patients with liver metastases",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<",
                                        "value": 5,
                                        "unit": "x ULN"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. Creatinine < or = 1,25 x upper normal value or creatinin-clearance > 50 ml/min (according to Cockroft Gault).",
            "criterions": [
                {
                    "exact_snippets": "Creatinine < or = 1,25 x upper normal value",
                    "criterion": "creatinine level",
                    "requirements": [
                        {
                            "requirement_type": "comparison",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.25,
                                "unit": "x upper normal value"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "creatinin-clearance > 50 ml/min (according to Cockroft Gault)",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "comparison",
                            "expected_value": {
                                "operator": ">",
                                "value": 50,
                                "unit": "ml/min"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "14. If of childbearing potential, negative pregnancy test. In addition the patient has to agree to use an effective method to avoid pregnancy for the duration of the study.",
            "criterions": [
                {
                    "exact_snippets": "If of childbearing potential",
                    "criterion": "childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "negative pregnancy test",
                    "criterion": "pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "agree to use an effective method to avoid pregnancy for the duration of the study",
                    "criterion": "use of effective method to avoid pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "15. Female and male patients",
            "criterions": [
                {
                    "exact_snippets": "Female and male patients",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "allowed_values",
                            "expected_value": [
                                "female",
                                "male"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "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": "1. Known hypersensitivity reaction to the compounds or incorporated substances or known dihydropyrimidine dehydrogenase deficiency.",
            "criterions": [
                {
                    "exact_snippets": "Known hypersensitivity reaction to the compounds or incorporated substances",
                    "criterion": "hypersensitivity reaction",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "known dihydropyrimidine dehydrogenase deficiency",
                    "criterion": "dihydropyrimidine dehydrogenase deficiency",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Concurrent immunotherapy or hormonal therapy (antihormonal, contraceptive and/or replacement therapy). Bisphosphonates may be continued.",
            "criterions": [
                {
                    "exact_snippets": "Concurrent immunotherapy",
                    "criterion": "immunotherapy",
                    "requirements": [
                        {
                            "requirement_type": "concurrency",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Concurrent ... hormonal therapy",
                    "criterion": "hormonal therapy",
                    "requirements": [
                        {
                            "requirement_type": "concurrency",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Bisphosphonates may be continued",
                    "criterion": "bisphosphonates",
                    "requirements": [
                        {
                            "requirement_type": "continuation",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Parenchymal brain metastases, unless adequately controlled by surgery and/or radiotherapy with complete resolution of symptoms and discontinuation of all steroids.",
            "criterions": [
                {
                    "exact_snippets": "Parenchymal brain metastases, unless adequately controlled by surgery and/or radiotherapy",
                    "criterion": "parenchymal brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": "adequately controlled by surgery and/or radiotherapy"
                        }
                    ]
                },
                {
                    "exact_snippets": "complete resolution of symptoms",
                    "criterion": "symptoms",
                    "requirements": [
                        {
                            "requirement_type": "resolution",
                            "expected_value": "complete"
                        }
                    ]
                },
                {
                    "exact_snippets": "discontinuation of all steroids",
                    "criterion": "steroid use",
                    "requirements": [
                        {
                            "requirement_type": "discontinuation",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Life expectancy of less than 3 months.",
            "criterions": [
                {
                    "exact_snippets": "Life expectancy of less than 3 months.",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": "<",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Serious intercurrent medical or psychiatric illness that may interfere with the planned treatment (including AIDS and serious active infection).",
            "criterions": [
                {
                    "exact_snippets": "Serious intercurrent medical or psychiatric illness",
                    "criterion": "intercurrent medical or psychiatric illness",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "serious"
                        }
                    ]
                },
                {
                    "exact_snippets": "AIDS",
                    "criterion": "AIDS",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "serious active infection",
                    "criterion": "active infection",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "serious"
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. History of other malignancy within the last 5 years which could affect the diagnosis or assessment of metastatic breast cancer.",
            "criterions": [
                {
                    "exact_snippets": "History of other malignancy within the last 5 years",
                    "criterion": "history of other malignancy",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 5,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Patients with indication for polychemotherapy.",
            "criterions": [
                {
                    "exact_snippets": "indication for polychemotherapy",
                    "criterion": "indication for polychemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry.",
            "criterions": [
                {
                    "exact_snippets": "Concurrent treatment with other experimental drugs.",
                    "criterion": "concurrent treatment with experimental drugs",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry.",
                    "criterion": "participation in another clinical trial",
                    "requirements": [
                        {
                            "requirement_type": "time since last participation",
                            "expected_value": {
                                "operator": ">=",
                                "value": 30,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Treatment with sorivudine or derivates e.g. brivudin.",
            "criterions": [
                {
                    "exact_snippets": "Treatment with sorivudine or derivates e.g. brivudin.",
                    "criterion": "treatment with sorivudine or derivates",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Pregnant or nursing women.",
            "criterions": [
                {
                    "exact_snippets": "Pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "nursing women",
                    "criterion": "nursing",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}