{
    "info": {
        "nct_id": "NCT01593020",
        "official_title": "A Randomized Phase II Neoadjuvant Study of Sequential Eribulin Followed by FAC/FEC-regimen Compared to Sequential Paclitaxel Followed by FAC/FEC-Regimen in Women With Early Stage Breast Cancer Not Overexpressing HER-2",
        "inclusion_criteria": "1. Signed written informed consent\n2. Histologically confirmed primary invasive adenocarcinoma of the breast.\n3. Clinical stage breast cancer T2-3, N0-3, M0\n4. Negative HER-2/neu expression as determined by local hospital laboratory using Fluorescence In Situ Hybridization (FISH), or is less or equal to 1+ using Immunohistochemistry (IHC).\n5. No prior treatment for primary invasive adenocarcinoma of the breast such as irradiation, chemotherapy, hormonal therapy, immunotherapy, investigational therapy or surgery. Subjects receiving hormone replacement treatment (HRT) are eligible if this therapy is discontinued at least 2 weeks before starting study treatment. Treatment for DCIS is allowed, such as surgery, hormonal therapy and radiotherapy.\n6. Karnofsky performance status (KPS) of 80 - 100\n7. The ability and willingness to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.\n8. Baseline MUGA or echocardiogram scans with LVEF of > 50%.\n9. Normal PTT and either INR or PT < 1.5 x ULN.\n10. Men or women 18 years of age or older.\n11. Women of childbearing potential (WOCBP) must agree to use a medically acceptable method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the last dose of study drugs.\n12. Willingness to have core biopsies and/or FNA performed before the start of study treatment and at the end of 12 week on treatment.\nHealthy volunteers allowed\nMust be FEMALE\nMust have minimum age of 18 Years",
        "exclusion_criteria": "1. Women who are pregnant (including positive pregnancy test at enrollment or prior to study drug administration) or breast-feeding.\n2. Disease free of prior malignancy for < 5 years with the exception of DCIS, curatively treated basal carcinoma of the skin, local skin squamous cell carcinoma, or carcinoma in situ of the cervix.\n3. Absolute neutrophils count (ANC) < 1500/mm^3\n4. Total bilirubin > 1.5 times the upper limit of normal (ULN)\n5. AST or ALT > 2.5 times the upper limit of normal (ULN)\n6. Platelets < 100,000/mm^3.\n7. Serum creatinine > 1.5 x ULN or creatinine clearance < 60 mL/min (measured or calculated by Cockcroft-Galt method)\n8. Evidence of metastatic breast cancer following a standard tumor staging work-up\n9. Evidence of inflammatory breast cancer.\n10. Evidence of any grade 2 sensory or motor neuropathy.\n11. Known human immunodeficiency viral (HIV) infection\n12. Serious intercurrent infections or non-malignant medical illness that are uncontrolled or the control of which may be jeopardized by this therapy.\n13. Psychiatric disorders or other conditions rendering the subject incapable of complying with the requirements of the protocols.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Signed written informed consent",
            "criterions": [
                {
                    "exact_snippets": "Signed written informed consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "signed",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "written",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Histologically confirmed primary invasive adenocarcinoma of the breast.",
            "criterions": [
                {
                    "exact_snippets": "Histologically confirmed primary invasive adenocarcinoma of the breast",
                    "criterion": "adenocarcinoma of the breast",
                    "requirements": [
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": "histologically"
                        },
                        {
                            "requirement_type": "invasiveness",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "primary",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Clinical stage breast cancer T2-3, N0-3, M0",
            "criterions": [
                {
                    "exact_snippets": "Clinical stage breast cancer",
                    "criterion": "breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "clinical"
                        }
                    ]
                },
                {
                    "exact_snippets": "T2-3",
                    "criterion": "tumor size",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 2,
                                        "unit": "T"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 3,
                                        "unit": "T"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "N0-3",
                    "criterion": "lymph node involvement",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 3,
                                        "unit": "N"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "M0",
                    "criterion": "distant metastasis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Negative HER-2/neu expression as determined by local hospital laboratory using Fluorescence In Situ Hybridization (FISH), or is less or equal to 1+ using Immunohistochemistry (IHC).",
            "criterions": [
                {
                    "exact_snippets": "Negative HER-2/neu expression as determined by local hospital laboratory using Fluorescence In Situ Hybridization (FISH)",
                    "criterion": "HER-2/neu expression",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": "Fluorescence In Situ Hybridization (FISH)"
                        },
                        {
                            "requirement_type": "expression",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "HER-2/neu expression ... is less or equal to 1+ using Immunohistochemistry (IHC)",
                    "criterion": "HER-2/neu expression",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": "Immunohistochemistry (IHC)"
                        },
                        {
                            "requirement_type": "expression",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "+"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. No prior treatment for primary invasive adenocarcinoma of the breast such as irradiation, chemotherapy, hormonal therapy, immunotherapy, investigational therapy or surgery. Subjects receiving hormone replacement treatment (HRT) are eligible if this therapy is discontinued at least 2 weeks before starting study treatment. Treatment for DCIS is allowed, such as surgery, hormonal therapy and radiotherapy.",
            "criterions": [
                {
                    "exact_snippets": "No prior treatment for primary invasive adenocarcinoma of the breast",
                    "criterion": "prior treatment for primary invasive adenocarcinoma of the breast",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Subjects receiving hormone replacement treatment (HRT) are eligible if this therapy is discontinued at least 2 weeks before starting study treatment",
                    "criterion": "hormone replacement treatment (HRT)",
                    "requirements": [
                        {
                            "requirement_type": "discontinuation period",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Karnofsky performance status (KPS) of 80 - 100",
            "criterions": [
                {
                    "exact_snippets": "Karnofsky performance status (KPS) of 80 - 100",
                    "criterion": "Karnofsky performance status (KPS)",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 80,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 100,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. The ability and willingness to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.",
            "criterions": [
                {
                    "exact_snippets": "The ability and willingness to comply with scheduled visits",
                    "criterion": "compliance with scheduled visits",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "The ability and willingness to comply with ... treatment plan",
                    "criterion": "compliance with treatment plan",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "The ability and willingness to comply with ... laboratory tests",
                    "criterion": "compliance with laboratory tests",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "The ability and willingness to comply with ... other study procedures",
                    "criterion": "compliance with other study procedures",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Baseline MUGA or echocardiogram scans with LVEF of > 50%.",
            "criterions": [
                {
                    "exact_snippets": "Baseline MUGA or echocardiogram scans",
                    "criterion": "MUGA or echocardiogram scans",
                    "requirements": [
                        {
                            "requirement_type": "baseline",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "LVEF of > 50%",
                    "criterion": "LVEF",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">",
                                "value": 50,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Normal PTT and either INR or PT < 1.5 x ULN.",
            "criterions": [
                {
                    "exact_snippets": "Normal PTT",
                    "criterion": "PTT",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": "normal"
                        }
                    ]
                },
                {
                    "exact_snippets": "either INR or PT < 1.5 x ULN",
                    "criterion": "INR or PT",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Men or women 18 years of age or older.",
            "criterions": [
                {
                    "exact_snippets": "Men or women",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "male",
                                "female"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "18 years of age or older",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Women of childbearing potential (WOCBP) must agree to use a medically acceptable method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the last dose of study drugs.",
            "criterions": [
                {
                    "exact_snippets": "Women of childbearing potential (WOCBP)",
                    "criterion": "women of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "must agree to use a medically acceptable method of contraception",
                    "criterion": "use of contraception",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "to avoid pregnancy throughout the study and for up to 8 weeks after the last dose of study drugs",
                    "criterion": "avoidance of pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "throughout the study and for up to 8 weeks after the last dose of study drugs"
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. Willingness to have core biopsies and/or FNA performed before the start of study treatment and at the end of 12 week on treatment.",
            "criterions": [
                {
                    "exact_snippets": "Willingness to have core biopsies and/or FNA performed before the start of study treatment",
                    "criterion": "willingness for core biopsies and/or FNA",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Willingness to have core biopsies and/or FNA performed ... at the end of 12 week on treatment",
                    "criterion": "willingness for core biopsies and/or FNA",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must 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": "1. Women who are pregnant (including positive pregnancy test at enrollment or prior to study drug administration) or breast-feeding.",
            "criterions": [
                {
                    "exact_snippets": "Women who are pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "positive pregnancy test at enrollment or prior to study drug administration",
                    "criterion": "pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "breast-feeding",
                    "criterion": "breast-feeding",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Disease free of prior malignancy for < 5 years with the exception of DCIS, curatively treated basal carcinoma of the skin, local skin squamous cell carcinoma, or carcinoma in situ of the cervix.",
            "criterions": [
                {
                    "exact_snippets": "Disease free of prior malignancy for < 5 years",
                    "criterion": "prior malignancy",
                    "requirements": [
                        {
                            "requirement_type": "disease-free duration",
                            "expected_value": {
                                "operator": "<",
                                "value": 5,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "with the exception of DCIS",
                    "criterion": "DCIS",
                    "requirements": [
                        {
                            "requirement_type": "exception",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "curatively treated basal carcinoma of the skin",
                    "criterion": "curatively treated basal carcinoma of the skin",
                    "requirements": [
                        {
                            "requirement_type": "exception",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "local skin squamous cell carcinoma",
                    "criterion": "local skin squamous cell carcinoma",
                    "requirements": [
                        {
                            "requirement_type": "exception",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "carcinoma in situ of the cervix",
                    "criterion": "carcinoma in situ of the cervix",
                    "requirements": [
                        {
                            "requirement_type": "exception",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Absolute neutrophils count (ANC) < 1500/mm^3",
            "criterions": [
                {
                    "exact_snippets": "Absolute neutrophils count (ANC) < 1500/mm^3",
                    "criterion": "absolute neutrophils count (ANC)",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<",
                                "value": 1500,
                                "unit": "mm^3"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Total bilirubin > 1.5 times the upper limit of normal (ULN)",
            "criterions": [
                {
                    "exact_snippets": "Total bilirubin > 1.5 times the upper limit of normal (ULN)",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">",
                                "value": 1.5,
                                "unit": "times the upper limit of normal (ULN)"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. AST or ALT > 2.5 times the upper limit of normal (ULN)",
            "criterions": [
                {
                    "exact_snippets": "AST or ALT > 2.5 times the upper limit of normal (ULN)",
                    "criterion": "AST",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">",
                                "value": 2.5,
                                "unit": "times ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "AST or ALT > 2.5 times the upper limit of normal (ULN)",
                    "criterion": "ALT",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">",
                                "value": 2.5,
                                "unit": "times ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Platelets < 100,000/mm^3.",
            "criterions": [
                {
                    "exact_snippets": "Platelets < 100,000/mm^3",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<",
                                "value": 100000,
                                "unit": "mm^3"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Serum creatinine > 1.5 x ULN or creatinine clearance < 60 mL/min (measured or calculated by Cockcroft-Galt method)",
            "criterions": [
                {
                    "exact_snippets": "Serum creatinine > 1.5 x ULN",
                    "criterion": "serum creatinine",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "creatinine clearance < 60 mL/min (measured or calculated by Cockcroft-Galt method)",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 60,
                                "unit": "mL/min"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Evidence of metastatic breast cancer following a standard tumor staging work-up",
            "criterions": [
                {
                    "exact_snippets": "Evidence of metastatic breast cancer",
                    "criterion": "metastatic breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "following a standard tumor staging work-up",
                    "criterion": "standard tumor staging work-up",
                    "requirements": [
                        {
                            "requirement_type": "completion",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Evidence of inflammatory breast cancer.",
            "criterions": [
                {
                    "exact_snippets": "Evidence of inflammatory breast cancer.",
                    "criterion": "inflammatory breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Evidence of any grade 2 sensory or motor neuropathy.",
            "criterions": [
                {
                    "exact_snippets": "any grade 2 sensory or motor neuropathy",
                    "criterion": "sensory neuropathy",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "grade 2"
                        }
                    ]
                },
                {
                    "exact_snippets": "any grade 2 sensory or motor neuropathy",
                    "criterion": "motor neuropathy",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "grade 2"
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Known human immunodeficiency viral (HIV) infection",
            "criterions": [
                {
                    "exact_snippets": "Known human immunodeficiency viral (HIV) infection",
                    "criterion": "HIV infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. Serious intercurrent infections or non-malignant medical illness that are uncontrolled or the control of which may be jeopardized by this therapy.",
            "criterions": [
                {
                    "exact_snippets": "Serious intercurrent infections",
                    "criterion": "intercurrent infections",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "serious"
                        },
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "non-malignant medical illness",
                    "criterion": "non-malignant medical illness",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. Psychiatric disorders or other conditions rendering the subject incapable of complying with the requirements of the protocols.",
            "criterions": [
                {
                    "exact_snippets": "Psychiatric disorders",
                    "criterion": "psychiatric disorders",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "other conditions rendering the subject incapable of complying with the requirements of the protocols",
                    "criterion": "conditions affecting protocol compliance",
                    "requirements": [
                        {
                            "requirement_type": "impact on compliance",
                            "expected_value": "incapable"
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}