{
    "info": {
        "nct_id": "NCT01545648",
        "official_title": "Pilot Study to Evaluate the Impact of Denosumab on Disseminated Tumor Cells (DTC) in Patients With Early Stage Breast Cancer",
        "inclusion_criteria": "1. Patients ≥18 years of age with histologically or cytologically confirmed stage I, II, or III breast cancer.\n2. ECOG Performance Status of 0 or 1\n3. Prior therapy:\n\n   1. Prior adjuvant therapy is not required for participation in this study.\n   2. If adjuvant or neoadjuvant treatment with chemotherapy is recommended, it must be completed before study start, and not more than 18 months prior to study start.\n   3. If adjuvant or neoadjuvant treatment with trastuzumab (Herceptin®) is recommended, patients should have received at least 3 months of therapy before eligibility bone marrow is performed.\n   4. Patients who have had surgery following neoadjuvant chemotherapy or hormonal therapy are eligible\n   5. Patients must have completed definitive surgery and have completely resected disease.\n   6. Concomitant hormonal therapy is allowed.\n   7. Concomitant adjuvant trastuzumab is permitted\n   8. If adjuvant hormonal treatment is recommended, patients should have received at least 3 months of therapy before screening bone marrow is performed.\n4. Bone marrow aspirate positive by IE/FC assay within 12 weeks of study entry\n\n   1. Definition of positive: >10 DTC/ml\n   2. Timing of bone marrow aspiration to determine study eligibility\n\n   i.If patient is to receive either no adjuvant therapy or hormonal therapy alone, the aspiration may be performed at diagnosis as part of the large micrometastasis study at UCSF, or following diagnosis if the patient received initial surgery elsewhere. This is also true for patients who have surgery following neoadjuvant therapy for breast cancer.\n\n   ii.If the patient is to receive adjuvant chemotherapy, the aspiration will be performed at least three weeks after chemotherapy has been completed.\n\n   iii.For trastuzumab and hormone therapy, see above.\n5. Laboratory studies\n\n   1. Liver function tests within normal limits, including total bilirubin, alkaline phosphatase, and AST (elevation of total bilirubin due to Gilbert's disease is allowed).\n\n      * Gilbert's disease: a common hereditary cause of increased indirect bilirubin, but with normal direct bilirubin.\n   2. Calculated creatinine clearance (calculated GFR) > 30 ml/min\n6. Ability to understand and sign informed consent\n7. Patients who have had surgery following neoadjuvant chemotherapy or hormonal therapy are eligible to participate in this trial.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "1. Karnofsky performance status < 90%\n2. Patients participating in this study are not allowed to receive bisphosphonate therapy during the study period, either oral or intravenous.\n3. Patients who completed adjuvant or neoadjuvant therapy more than 18 months prior to study screening.\n4. A history of malignancy within the last 5 years except basal cell carcinoma of skin.\n5. A history of human immunodeficiency virus (HIV) infection.\n6. Severe, concurrent illness that would likely prevent the patient from being able to comply with the study protocol.\n7. Pregnant or lactating women and women of child-bearing potential who are not using an effective method of birth control.\n8. Significant dental disease that requires major intervention during the study period, such as tooth extraction\n9. Significant coagulopathy that would prevent safe bone marrow aspiration",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Patients ≥18 years of age with histologically or cytologically confirmed stage I, II, or III breast cancer.",
            "criterions": [
                {
                    "exact_snippets": "Patients ≥18 years of age",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "histologically or cytologically confirmed",
                    "criterion": "confirmation method",
                    "requirements": [
                        {
                            "requirement_type": "methods",
                            "expected_value": [
                                "histologically",
                                "cytologically"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "stage I, II, or III breast cancer",
                    "criterion": "breast cancer stage",
                    "requirements": [
                        {
                            "requirement_type": "stages",
                            "expected_value": [
                                "I",
                                "II",
                                "III"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. ECOG Performance Status of 0 or 1",
            "criterions": [
                {
                    "exact_snippets": "ECOG Performance Status of 0 or 1",
                    "criterion": "ECOG Performance Status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": [
                                "0",
                                "1"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Prior therapy:",
            "criterions": [
                {
                    "exact_snippets": "Prior therapy",
                    "criterion": "prior therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Prior adjuvant therapy is not required for participation in this study.",
            "criterions": [
                {
                    "exact_snippets": "Prior adjuvant therapy is not required",
                    "criterion": "prior adjuvant therapy",
                    "requirements": [
                        {
                            "requirement_type": "requirement",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. If adjuvant or neoadjuvant treatment with chemotherapy is recommended, it must be completed before study start, and not more than 18 months prior to study start.",
            "criterions": [
                {
                    "exact_snippets": "adjuvant or neoadjuvant treatment with chemotherapy is recommended",
                    "criterion": "adjuvant or neoadjuvant chemotherapy treatment",
                    "requirements": [
                        {
                            "requirement_type": "recommendation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "adjuvant or neoadjuvant treatment with chemotherapy ... must be completed before study start",
                    "criterion": "completion of chemotherapy treatment",
                    "requirements": [
                        {
                            "requirement_type": "completion",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "adjuvant or neoadjuvant treatment with chemotherapy ... not more than 18 months prior to study start",
                    "criterion": "timing of chemotherapy treatment",
                    "requirements": [
                        {
                            "requirement_type": "time since completion",
                            "expected_value": {
                                "operator": "<=",
                                "value": 18,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. If adjuvant or neoadjuvant treatment with trastuzumab (Herceptin®) is recommended, patients should have received at least 3 months of therapy before eligibility bone marrow is performed.",
            "criterions": [
                {
                    "exact_snippets": "adjuvant or neoadjuvant treatment with trastuzumab (Herceptin®) is recommended",
                    "criterion": "trastuzumab (Herceptin®) treatment",
                    "requirements": [
                        {
                            "requirement_type": "recommendation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "patients should have received at least 3 months of therapy",
                    "criterion": "trastuzumab (Herceptin®) treatment duration",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Patients who have had surgery following neoadjuvant chemotherapy or hormonal therapy are eligible",
            "criterions": [
                {
                    "exact_snippets": "Patients who have had surgery following neoadjuvant chemotherapy",
                    "criterion": "surgery following neoadjuvant chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients who have had surgery following ... hormonal therapy",
                    "criterion": "surgery following hormonal therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Patients must have completed definitive surgery and have completely resected disease.",
            "criterions": [
                {
                    "exact_snippets": "Patients must have completed definitive surgery",
                    "criterion": "definitive surgery",
                    "requirements": [
                        {
                            "requirement_type": "completion",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "completely resected disease",
                    "criterion": "disease resection",
                    "requirements": [
                        {
                            "requirement_type": "completeness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Concomitant hormonal therapy is allowed.",
            "criterions": [
                {
                    "exact_snippets": "Concomitant hormonal therapy is allowed.",
                    "criterion": "concomitant hormonal therapy",
                    "requirements": [
                        {
                            "requirement_type": "allowance",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Concomitant adjuvant trastuzumab is permitted",
            "criterions": [
                {
                    "exact_snippets": "Concomitant adjuvant trastuzumab is permitted",
                    "criterion": "concomitant adjuvant trastuzumab",
                    "requirements": [
                        {
                            "requirement_type": "permitted",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. If adjuvant hormonal treatment is recommended, patients should have received at least 3 months of therapy before screening bone marrow is performed.",
            "criterions": [
                {
                    "exact_snippets": "adjuvant hormonal treatment is recommended",
                    "criterion": "adjuvant hormonal treatment",
                    "requirements": [
                        {
                            "requirement_type": "recommendation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "patients should have received at least 3 months of therapy",
                    "criterion": "duration of adjuvant hormonal therapy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Bone marrow aspirate positive by IE/FC assay within 12 weeks of study entry",
            "criterions": [
                {
                    "exact_snippets": "Bone marrow aspirate positive by IE/FC assay",
                    "criterion": "bone marrow aspirate",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "positive"
                        }
                    ]
                },
                {
                    "exact_snippets": "within 12 weeks of study entry",
                    "criterion": "time since test",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": "<=",
                                "value": 12,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Definition of positive: >10 DTC/ml",
            "criterions": [
                {
                    "exact_snippets": "positive: >10 DTC/ml",
                    "criterion": "DTC",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">",
                                "value": 10,
                                "unit": "DTC/ml"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Timing of bone marrow aspiration to determine study eligibility",
            "criterions": [
                {
                    "exact_snippets": "Timing of bone marrow aspiration",
                    "criterion": "bone marrow aspiration",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "to determine study eligibility"
                        }
                    ]
                }
            ]
        },
        {
            "line": "i.If patient is to receive either no adjuvant therapy or hormonal therapy alone, the aspiration may be performed at diagnosis as part of the large micrometastasis study at UCSF, or following diagnosis if the patient received initial surgery elsewhere. This is also true for patients who have surgery following neoadjuvant therapy for breast cancer.",
            "criterions": [
                {
                    "exact_snippets": "patient is to receive either no adjuvant therapy or hormonal therapy alone",
                    "criterion": "adjuvant therapy",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "none",
                                "hormonal therapy alone"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "patients who have surgery following neoadjuvant therapy for breast cancer",
                    "criterion": "neoadjuvant therapy for breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "surgery following",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "ii.If the patient is to receive adjuvant chemotherapy, the aspiration will be performed at least three weeks after chemotherapy has been completed.",
            "criterions": [
                {
                    "exact_snippets": "patient is to receive adjuvant chemotherapy",
                    "criterion": "adjuvant chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "intention",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "aspiration will be performed at least three weeks after chemotherapy has been completed",
                    "criterion": "aspiration timing",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "iii.For trastuzumab and hormone therapy, see above.",
            "criterions": [
                {
                    "exact_snippets": "trastuzumab",
                    "criterion": "trastuzumab",
                    "requirements": [
                        {
                            "requirement_type": "see above",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "hormone therapy",
                    "criterion": "hormone therapy",
                    "requirements": [
                        {
                            "requirement_type": "see above",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Laboratory studies",
            "criterions": [
                {
                    "exact_snippets": "Laboratory studies",
                    "criterion": "laboratory studies",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. Liver function tests within normal limits, including total bilirubin, alkaline phosphatase, and AST (elevation of total bilirubin due to Gilbert's disease is allowed).",
            "criterions": [
                {
                    "exact_snippets": "Liver function tests within normal limits",
                    "criterion": "liver function tests",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": "within normal limits"
                        }
                    ]
                },
                {
                    "exact_snippets": "total bilirubin",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": "within normal limits"
                        }
                    ]
                },
                {
                    "exact_snippets": "alkaline phosphatase",
                    "criterion": "alkaline phosphatase",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": "within normal limits"
                        }
                    ]
                },
                {
                    "exact_snippets": "AST",
                    "criterion": "AST",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": "within normal limits"
                        }
                    ]
                },
                {
                    "exact_snippets": "elevation of total bilirubin due to Gilbert's disease is allowed",
                    "criterion": "total bilirubin elevation due to Gilbert's disease",
                    "requirements": [
                        {
                            "requirement_type": "allowance",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Gilbert's disease: a common hereditary cause of increased indirect bilirubin, but with normal direct bilirubin.",
            "criterions": [
                {
                    "exact_snippets": "Gilbert's disease: a common hereditary cause of increased indirect bilirubin",
                    "criterion": "Gilbert's disease",
                    "requirements": [
                        {
                            "requirement_type": "cause",
                            "expected_value": "increased indirect bilirubin"
                        }
                    ]
                },
                {
                    "exact_snippets": "normal direct bilirubin",
                    "criterion": "direct bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": "normal"
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Calculated creatinine clearance (calculated GFR) > 30 ml/min",
            "criterions": [
                {
                    "exact_snippets": "Calculated creatinine clearance (calculated GFR) > 30 ml/min",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "calculated value",
                            "expected_value": {
                                "operator": ">",
                                "value": 30,
                                "unit": "ml/min"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Ability to understand and sign informed consent",
            "criterions": [
                {
                    "exact_snippets": "Ability to understand",
                    "criterion": "cognitive ability",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "sign informed consent",
                    "criterion": "ability to sign informed consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Patients who have had surgery following neoadjuvant chemotherapy or hormonal therapy are eligible to participate in this trial.",
            "criterions": [
                {
                    "exact_snippets": "Patients who have had surgery following neoadjuvant chemotherapy",
                    "criterion": "surgery following neoadjuvant chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients who have had surgery following ... hormonal therapy",
                    "criterion": "surgery following hormonal therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "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": "1. Karnofsky performance status < 90%",
            "criterions": [
                {
                    "exact_snippets": "Karnofsky performance status < 90%",
                    "criterion": "Karnofsky performance status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<",
                                "value": 90,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Patients participating in this study are not allowed to receive bisphosphonate therapy during the study period, either oral or intravenous.",
            "criterions": [
                {
                    "exact_snippets": "not allowed to receive bisphosphonate therapy during the study period, either oral or intravenous",
                    "criterion": "bisphosphonate therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Patients who completed adjuvant or neoadjuvant therapy more than 18 months prior to study screening.",
            "criterions": [
                {
                    "exact_snippets": "Patients who completed adjuvant or neoadjuvant therapy",
                    "criterion": "completion of adjuvant or neoadjuvant therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since completion",
                            "expected_value": {
                                "operator": ">",
                                "value": 18,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. A history of malignancy within the last 5 years except basal cell carcinoma of skin.",
            "criterions": [
                {
                    "exact_snippets": "A history of malignancy within the last 5 years",
                    "criterion": "history of malignancy",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 5,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "except basal cell carcinoma of skin",
                    "criterion": "basal cell carcinoma of skin",
                    "requirements": [
                        {
                            "requirement_type": "exclusion",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. A history of human immunodeficiency virus (HIV) infection.",
            "criterions": [
                {
                    "exact_snippets": "A history of human immunodeficiency virus (HIV) infection.",
                    "criterion": "HIV infection",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Severe, concurrent illness that would likely prevent the patient from being able to comply with the study protocol.",
            "criterions": [
                {
                    "exact_snippets": "Severe, concurrent illness",
                    "criterion": "concurrent illness",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Pregnant or lactating women and women of child-bearing potential who are not using an effective method of birth control.",
            "criterions": [
                {
                    "exact_snippets": "Pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "lactating women",
                    "criterion": "lactation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "women of child-bearing potential",
                    "criterion": "women of child-bearing potential",
                    "requirements": [
                        {
                            "requirement_type": "birth control usage",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Significant dental disease that requires major intervention during the study period, such as tooth extraction",
            "criterions": [
                {
                    "exact_snippets": "Significant dental disease that requires major intervention during the study period, such as tooth extraction",
                    "criterion": "dental disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "significant"
                        },
                        {
                            "requirement_type": "intervention",
                            "expected_value": "major"
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Significant coagulopathy that would prevent safe bone marrow aspiration",
            "criterions": [
                {
                    "exact_snippets": "Significant coagulopathy",
                    "criterion": "coagulopathy",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "significant"
                        }
                    ]
                },
                {
                    "exact_snippets": "prevent safe bone marrow aspiration",
                    "criterion": "bone marrow aspiration",
                    "requirements": [
                        {
                            "requirement_type": "safety",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}