{
    "info": {
        "nct_id": "NCT00470301",
        "official_title": "A Phase I-II Study of R115777 (Tipifarnib, Zarnestra®) Plus Sequential Weekly Paclitaxel Followed by Dose-Dense Doxorubicin and Cyclophosphamide in Patients With Stage IIB-IIIC Breast Cancer",
        "inclusion_criteria": "* Histologically or cytologically confirmed adenocarcinoma of the breast; clinical stage IIB, IIIA, IIIB, or IIIC disease\n* At least 1 week since prior tamoxifen or other selective estrogen receptor modulator for prevention or for other indications (e.g., osteoporosis or prior ductal carcinoma in situ)\n* HER-2/neu-negative by immunohistochemistry or fluorescence in situ hybridization (FISH)\n* Hormone receptor status:\n\n  * Estrogen and/or progesterone receptor-positive* [Note: *Patients enrolled on the phase I portion of the trial may have estrogen and progesterone receptor-negative disease]\n* Normal organ function including:\n* WBC >= 3,000/mm^3\n* Absolute neutrophil count >= 1,500/mm^3\n* Platelet count >= 100,000/mm^3\n* Bilirubin normal\n* AST and ALT =< 2.5 times upper limit of normal\n* LVEF normal by echocardiogram or nuclear scan\n* Creatinine normal OR Creatinine clearance >= 60 mL/min\n* FEV1 >= 1 L* and DLCO >= 50%* [Note: *Only if baseline CT scan of chest shows parenchymal lung disease OR there is a history of chronic obstructive or other pulmonary disease]\n* No prior chemotherapy, radiotherapy, or definitive therapeutic surgery (e.g., mastectomy, lumpectomy, or axillary dissection) for this cancer but prior sentinel lymph node biopsy for this malignancy allowed\n* No prior adjuvant chemotherapy for a previous breast malignancy\n* No concurrent combination antiretroviral therapy for HIV-positive patients\n* No other concurrent investigational agents\n* No other concurrent anticancer agents or therapies\n* ECOG performance status 0-1\n* Fertile patients must use effective contraception\n\nExclusion criteria:\n\n* No other invasive malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix\n* No history of allergic reactions attributed to compounds of similar chemical or biological composition to tipifarnib or other study drugs (e.g., imidazoles or quinolones)\n* No other uncontrolled illness including, but not limited to, any of the following: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/social situations that would preclude study compliance\n* Not pregnant or nursing\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Histologically or cytologically confirmed adenocarcinoma of the breast; clinical stage IIB, IIIA, IIIB, or IIIC disease",
            "criterions": [
                {
                    "exact_snippets": "Histologically or cytologically confirmed adenocarcinoma of the breast",
                    "criterion": "adenocarcinoma of the breast",
                    "requirements": [
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": [
                                "histologically",
                                "cytologically"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "clinical stage IIB, IIIA, IIIB, or IIIC disease",
                    "criterion": "clinical stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "IIB",
                                "IIIA",
                                "IIIB",
                                "IIIC"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* At least 1 week since prior tamoxifen or other selective estrogen receptor modulator for prevention or for other indications (e.g., osteoporosis or prior ductal carcinoma in situ)",
            "criterions": [
                {
                    "exact_snippets": "At least 1 week since prior tamoxifen or other selective estrogen receptor modulator",
                    "criterion": "time since prior selective estrogen receptor modulator",
                    "requirements": [
                        {
                            "requirement_type": "time since last use",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "week"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* HER-2/neu-negative by immunohistochemistry or fluorescence in situ hybridization (FISH)",
            "criterions": [
                {
                    "exact_snippets": "HER-2/neu-negative by immunohistochemistry or fluorescence in situ hybridization (FISH)",
                    "criterion": "HER-2/neu status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "negative"
                        },
                        {
                            "requirement_type": "testing method",
                            "expected_value": [
                                "immunohistochemistry",
                                "fluorescence in situ hybridization (FISH)"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Hormone receptor status:",
            "criterions": [
                {
                    "exact_snippets": "Hormone receptor status",
                    "criterion": "hormone receptor status",
                    "requirements": [
                        {
                            "requirement_type": "N/A",
                            "expected_value": "N/A"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Estrogen and/or progesterone receptor-positive* [Note: *Patients enrolled on the phase I portion of the trial may have estrogen and progesterone receptor-negative disease]",
            "criterions": [
                {
                    "exact_snippets": "Estrogen and/or progesterone receptor-positive",
                    "criterion": "hormone receptor status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": [
                                "estrogen receptor-positive",
                                "progesterone receptor-positive"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Normal organ function including:",
            "criterions": [
                {
                    "exact_snippets": "Normal organ function",
                    "criterion": "organ function",
                    "requirements": [
                        {
                            "requirement_type": "condition",
                            "expected_value": "normal"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* WBC >= 3,000/mm^3",
            "criterions": [
                {
                    "exact_snippets": "WBC >= 3,000/mm^3",
                    "criterion": "WBC",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3000,
                                "unit": "mm^3"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Absolute neutrophil count >= 1,500/mm^3",
            "criterions": [
                {
                    "exact_snippets": "Absolute neutrophil count >= 1,500/mm^3",
                    "criterion": "absolute neutrophil count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1500,
                                "unit": "mm^3"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Platelet count >= 100,000/mm^3",
            "criterions": [
                {
                    "exact_snippets": "Platelet count >= 100,000/mm^3",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100000,
                                "unit": "mm^3"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Bilirubin normal",
            "criterions": [
                {
                    "exact_snippets": "Bilirubin normal",
                    "criterion": "bilirubin level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": "normal"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* AST and ALT =< 2.5 times upper limit of normal",
            "criterions": [
                {
                    "exact_snippets": "AST ... =< 2.5 times upper limit of normal",
                    "criterion": "AST",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "times upper limit of normal"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "ALT =< 2.5 times upper limit of normal",
                    "criterion": "ALT",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "times upper limit of normal"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* LVEF normal by echocardiogram or nuclear scan",
            "criterions": [
                {
                    "exact_snippets": "LVEF normal by echocardiogram or nuclear scan",
                    "criterion": "LVEF",
                    "requirements": [
                        {
                            "requirement_type": "normality",
                            "expected_value": "normal"
                        },
                        {
                            "requirement_type": "assessment method",
                            "expected_value": [
                                "echocardiogram",
                                "nuclear scan"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Creatinine normal OR Creatinine clearance >= 60 mL/min",
            "criterions": [
                {
                    "exact_snippets": "Creatinine normal",
                    "criterion": "creatinine",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": "normal"
                        }
                    ]
                },
                {
                    "exact_snippets": "Creatinine clearance >= 60 mL/min",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 60,
                                "unit": "mL/min"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* FEV1 >= 1 L* and DLCO >= 50%* [Note: *Only if baseline CT scan of chest shows parenchymal lung disease OR there is a history of chronic obstructive or other pulmonary disease]",
            "criterions": [
                {
                    "exact_snippets": "FEV1 >= 1 L",
                    "criterion": "FEV1",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "DLCO >= 50%",
                    "criterion": "DLCO",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 50,
                                "unit": "%"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "baseline CT scan of chest shows parenchymal lung disease",
                    "criterion": "parenchymal lung disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "history of chronic obstructive or other pulmonary disease",
                    "criterion": "chronic obstructive or other pulmonary disease",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* No prior chemotherapy, radiotherapy, or definitive therapeutic surgery (e.g., mastectomy, lumpectomy, or axillary dissection) for this cancer but prior sentinel lymph node biopsy for this malignancy allowed",
            "criterions": [
                {
                    "exact_snippets": "No prior chemotherapy",
                    "criterion": "prior chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "No prior ... radiotherapy",
                    "criterion": "prior radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "No prior ... definitive therapeutic surgery",
                    "criterion": "prior definitive therapeutic surgery",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "prior sentinel lymph node biopsy for this malignancy allowed",
                    "criterion": "prior sentinel lymph node biopsy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* No prior adjuvant chemotherapy for a previous breast malignancy",
            "criterions": [
                {
                    "exact_snippets": "No prior adjuvant chemotherapy for a previous breast malignancy",
                    "criterion": "prior adjuvant chemotherapy for a previous breast malignancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* No concurrent combination antiretroviral therapy for HIV-positive patients",
            "criterions": [
                {
                    "exact_snippets": "No concurrent combination antiretroviral therapy for HIV-positive patients",
                    "criterion": "combination antiretroviral therapy",
                    "requirements": [
                        {
                            "requirement_type": "concurrency",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* No other concurrent investigational agents",
            "criterions": [
                {
                    "exact_snippets": "No other concurrent investigational agents",
                    "criterion": "concurrent investigational agents",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* No other concurrent anticancer agents or therapies",
            "criterions": [
                {
                    "exact_snippets": "No other concurrent anticancer agents or therapies",
                    "criterion": "concurrent anticancer agents or therapies",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* ECOG performance status 0-1",
            "criterions": [
                {
                    "exact_snippets": "ECOG performance status 0-1",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 1,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Fertile patients must use effective contraception",
            "criterions": [
                {
                    "exact_snippets": "Fertile patients",
                    "criterion": "fertility",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "fertile"
                        }
                    ]
                },
                {
                    "exact_snippets": "must use effective contraception",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* No other invasive malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix",
            "criterions": [
                {
                    "exact_snippets": "No other invasive malignancy within the past 5 years",
                    "criterion": "invasive malignancy",
                    "requirements": [
                        {
                            "requirement_type": "time since last occurrence",
                            "expected_value": {
                                "operator": "<",
                                "value": 5,
                                "unit": "years"
                            }
                        },
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "except curatively treated basal cell or squamous cell skin cancer",
                    "criterion": "curatively treated basal cell or squamous cell skin cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "except ... carcinoma in situ of the cervix",
                    "criterion": "carcinoma in situ of the cervix",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* No history of allergic reactions attributed to compounds of similar chemical or biological composition to tipifarnib or other study drugs (e.g., imidazoles or quinolones)",
            "criterions": [
                {
                    "exact_snippets": "No history of allergic reactions attributed to compounds of similar chemical or biological composition to tipifarnib or other study drugs (e.g., imidazoles or quinolones)",
                    "criterion": "allergic reactions to compounds similar to tipifarnib or other study drugs",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* No other uncontrolled illness including, but not limited to, any of the following: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/social situations that would preclude study compliance",
            "criterions": [
                {
                    "exact_snippets": "uncontrolled illness ... ongoing or active infection",
                    "criterion": "ongoing or active infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled illness ... symptomatic congestive heart failure",
                    "criterion": "symptomatic congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled illness ... unstable angina pectoris",
                    "criterion": "unstable angina pectoris",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled illness ... cardiac arrhythmia",
                    "criterion": "cardiac arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled illness ... psychiatric illness/social situations that would preclude study compliance",
                    "criterion": "psychiatric illness/social situations",
                    "requirements": [
                        {
                            "requirement_type": "impact on study compliance",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "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": [],
    "miscellaneous_lines": [],
    "failed_inclusion": [
        {
            "line": "Exclusion criteria:",
            "criterions": []
        },
        {
            "line": "* Not pregnant or nursing",
            "criterions": [
                {
                    "exact_snippets": "Not pregnant",
                    "criterion": "pregnancy status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "not ... nursing",
                    "criterion": "nursing status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}