{
    "info": {
        "nct_id": "NCT01847976",
        "official_title": "A Phase 2 Trial Exploring the Clinical and Correlative Effects of Combining Doxycycline With Bone-Targeted Therapy in Patients With Metastatic Breast Cancer",
        "inclusion_criteria": "1. Patients with metastatic breast cancer with radiologically confirmed bone metastases.\n2. On intravenous bone-targeted therapy (bisphosphonate or subcutaneous (SC) denosumab) for at least 3 months.\n3. ECOG ≤ 2\n4. Life expectancy >3 months.\n5. No changes in the type of systemic chemotherapy, endocrine therapy or biological therapy (i.e. trastuzumab, lapatinib) treatment in the 4 weeks prior to study entry or anticipated changes in the 4 weeks after entering the study. (Markers of bone formation can be affected by a change in systemic therapies).\n6. Ability to provide informed consent and complete study evaluations.\nHealthy volunteers allowed\nMust be FEMALE\nMust have minimum age of 19 Years",
        "exclusion_criteria": "1. Prior hypersensitivity to either IV bisphosphonate therapy or SC denosumab, doxycycline or tetracyclines.\n2. Patients with myasthenia gravis\n3. Patients taking hepatic enzymes inducers such as phenytoin, barbiturates and carbamazepine\n4. Patients with rapidly progressive non-bone metastases for whom delaying a change in systemic anti-cancer treatment in the first 4 weeks of the study could have a detrimental impact on patient outcome.\n5. Women of child bearing potential who are unwilling to use acceptable methods of contraception while on study.\n6. Pregnancy or lactation.\n7. Clotting disorder that would preclude bone marrow aspirate and trephine biopsy. (Patients on Fragmin or Daltaperin are allowed on study)",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Patients with metastatic breast cancer with radiologically confirmed bone metastases.",
            "criterions": [
                {
                    "exact_snippets": "metastatic breast cancer",
                    "criterion": "breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "metastatic",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "radiologically confirmed bone metastases",
                    "criterion": "bone metastases",
                    "requirements": [
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": "radiologically confirmed"
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. On intravenous bone-targeted therapy (bisphosphonate or subcutaneous (SC) denosumab) for at least 3 months.",
            "criterions": [
                {
                    "exact_snippets": "On intravenous bone-targeted therapy (bisphosphonate or subcutaneous (SC) denosumab)",
                    "criterion": "bone-targeted therapy",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "intravenous bisphosphonate",
                                "subcutaneous denosumab"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "for at least 3 months",
                    "criterion": "duration of therapy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. ECOG ≤ 2",
            "criterions": [
                {
                    "exact_snippets": "ECOG ≤ 2",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "performance status",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "N/A"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. 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"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. No changes in the type of systemic chemotherapy, endocrine therapy or biological therapy (i.e. trastuzumab, lapatinib) treatment in the 4 weeks prior to study entry or anticipated changes in the 4 weeks after entering the study. (Markers of bone formation can be affected by a change in systemic therapies).",
            "criterions": [
                {
                    "exact_snippets": "No changes in the type of systemic chemotherapy ... in the 4 weeks prior to study entry",
                    "criterion": "systemic chemotherapy type",
                    "requirements": [
                        {
                            "requirement_type": "change",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "No changes in the type of systemic chemotherapy ... anticipated changes in the 4 weeks after entering the study",
                    "criterion": "systemic chemotherapy type",
                    "requirements": [
                        {
                            "requirement_type": "anticipated change",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "No changes in the type of ... endocrine therapy ... in the 4 weeks prior to study entry",
                    "criterion": "endocrine therapy type",
                    "requirements": [
                        {
                            "requirement_type": "change",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "No changes in the type of ... endocrine therapy ... anticipated changes in the 4 weeks after entering the study",
                    "criterion": "endocrine therapy type",
                    "requirements": [
                        {
                            "requirement_type": "anticipated change",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "No changes in the type of ... biological therapy (i.e. trastuzumab, lapatinib) ... in the 4 weeks prior to study entry",
                    "criterion": "biological therapy type",
                    "requirements": [
                        {
                            "requirement_type": "change",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "No changes in the type of ... biological therapy (i.e. trastuzumab, lapatinib) ... anticipated changes in the 4 weeks after entering the study",
                    "criterion": "biological therapy type",
                    "requirements": [
                        {
                            "requirement_type": "anticipated change",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Ability to provide informed consent and complete study evaluations.",
            "criterions": [
                {
                    "exact_snippets": "Ability to provide informed consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Ability to ... complete study evaluations",
                    "criterion": "study evaluations",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "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 be FEMALE",
            "criterions": [
                {
                    "exact_snippets": "Must be FEMALE",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "expected_value",
                            "expected_value": "female"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have minimum age of 19 Years",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 19 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 19,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "1. Prior hypersensitivity to either IV bisphosphonate therapy or SC denosumab, doxycycline or tetracyclines.",
            "criterions": [
                {
                    "exact_snippets": "Prior hypersensitivity to either IV bisphosphonate therapy",
                    "criterion": "hypersensitivity to IV bisphosphonate therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior hypersensitivity to ... SC denosumab",
                    "criterion": "hypersensitivity to SC denosumab",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior hypersensitivity to ... doxycycline",
                    "criterion": "hypersensitivity to doxycycline",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior hypersensitivity to ... tetracyclines",
                    "criterion": "hypersensitivity to tetracyclines",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Patients with myasthenia gravis",
            "criterions": [
                {
                    "exact_snippets": "Patients with myasthenia gravis",
                    "criterion": "myasthenia gravis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Patients taking hepatic enzymes inducers such as phenytoin, barbiturates and carbamazepine",
            "criterions": [
                {
                    "exact_snippets": "Patients taking hepatic enzymes inducers such as phenytoin, barbiturates and carbamazepine",
                    "criterion": "hepatic enzyme inducers",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Patients with rapidly progressive non-bone metastases for whom delaying a change in systemic anti-cancer treatment in the first 4 weeks of the study could have a detrimental impact on patient outcome.",
            "criterions": [
                {
                    "exact_snippets": "rapidly progressive non-bone metastases",
                    "criterion": "metastases",
                    "requirements": [
                        {
                            "requirement_type": "progression",
                            "expected_value": "rapidly progressive"
                        },
                        {
                            "requirement_type": "location",
                            "expected_value": "non-bone"
                        }
                    ]
                },
                {
                    "exact_snippets": "delaying a change in systemic anti-cancer treatment in the first 4 weeks of the study could have a detrimental impact on patient outcome",
                    "criterion": "impact of treatment delay",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "first 4 weeks of the study"
                        },
                        {
                            "requirement_type": "impact",
                            "expected_value": "detrimental"
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Women of child bearing potential who are unwilling to use acceptable methods of contraception while on study.",
            "criterions": [
                {
                    "exact_snippets": "Women of child bearing potential",
                    "criterion": "child bearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "unwilling to use acceptable methods of contraception",
                    "criterion": "use of contraception",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Pregnancy or lactation.",
            "criterions": [
                {
                    "exact_snippets": "Pregnancy",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "lactation",
                    "criterion": "lactation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Clotting disorder that would preclude bone marrow aspirate and trephine biopsy. (Patients on Fragmin or Daltaperin are allowed on study)",
            "criterions": [
                {
                    "exact_snippets": "Clotting disorder that would preclude bone marrow aspirate and trephine biopsy.",
                    "criterion": "clotting disorder",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "would preclude bone marrow aspirate and trephine biopsy"
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients on Fragmin or Daltaperin are allowed on study",
                    "criterion": "medication",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "Fragmin",
                                "Daltaperin"
                            ]
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}