{
    "info": {
        "nct_id": "NCT01056757",
        "official_title": "A Phase I/II Exploratory Study of Ribavirin in Metastatic Breast Cancer Expressing Elevated eIF4E",
        "inclusion_criteria": "* Histologically or cytologically confirmed breast cancer at diagnosis, with metastatic disease at the time of screening, who have progressed on prior anthracycline and taxane-containing regimens.\n* Willing to have a screening biopsy performed from an easily accessible lesion (ex. skin, superficial lymph node), AND must have overexpression of eIF4E in the metastatic tissue.\n* Easily accessible lesion for serial biopsies (ex. skin, superficial lymph node, or other easily accessible site).\n* At least 1 unidimensionally measurable lesion (based on the RECIST criteria) outside the CNS.\n* ECOG 0, 1, or 2.\n* Adequate recovery (excluding alopecia) from previous surgery, radiation, and chemotherapy.\n* Adequate wash-out period from last therapy for breast cancer (at least 3 weeks).\n* Life expectancy ≥ 12 weeks.\n* Age is ≥ 18 years. There is no upper age limit since the drug can be administered orally and even considered in a palliative setting.\n* Female patients of childbearing potential must have a negative serum (beta-HCG) pregnancy test within 14 days of starting protocol and must not be breastfeeding. Men and women of childbearing potential must agree to use an effective means of contraception throughout the study and for at least 6 months after completion of protocol. Post-menopausal women (defined as 12 or more consecutive months of amenorrhea, or follicle stimulating hormone (FSH) in the post-menopausal range), or surgically sterile women, do not require methods of contraception.\n* Adequate renal and hepatic function: serum creatinine < 1.5 x ULN; AST or ALT < 2.5 x ULN (or < 5 x ULN if liver involvement with metastases); serum bilirubin < 1.5 x ULN.\n* Adequate hematopoietic function: neutrophils ≥1.0 x 10E9/L, platelets ≥ 100 x 10E9/L.\n* Provide written consent after the investigational nature, study design, risks and benefits of the study have been explained.\n* Accessible for treatment and follow up.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Symptomatic brain metastases.\n* Active cardiovascular disease as defined by New York Heart Association (NYHA) class III-IV categorization.\n* Intercurrent illness or medical condition precluding safe administration of the planned protocol treatment or required follow-up.\n* Use of any investigational drug within 4 weeks before start of study treatment or inadequate recovery from any toxic effects of such therapy.\n* Female patients who are pregnant or breastfeeding.\n* Concurrent treatment with other anti-cancer therapy. Bisphosphonates are allowed as long as they were started prior to screening (at least 4 weeks before study entry) and the dose does not change during study participation.\n* Known infection with HIV.\n* History of other malignancy in the past 5 years. Subjects who have been disease-free for 1 year or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Histologically or cytologically confirmed breast cancer at diagnosis, with metastatic disease at the time of screening, who have progressed on prior anthracycline and taxane-containing regimens.",
            "criterions": [
                {
                    "exact_snippets": "Histologically or cytologically confirmed breast cancer",
                    "criterion": "breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": [
                                "histologically",
                                "cytologically"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "metastatic disease at the time of screening",
                    "criterion": "metastatic disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "progressed on prior anthracycline and taxane-containing regimens",
                    "criterion": "progression on prior regimens",
                    "requirements": [
                        {
                            "requirement_type": "regimen type",
                            "expected_value": [
                                "anthracycline",
                                "taxane"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Willing to have a screening biopsy performed from an easily accessible lesion (ex. skin, superficial lymph node), AND must have overexpression of eIF4E in the metastatic tissue.",
            "criterions": [
                {
                    "exact_snippets": "Willing to have a screening biopsy performed",
                    "criterion": "willingness for screening biopsy",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "easily accessible lesion (ex. skin, superficial lymph node)",
                    "criterion": "lesion accessibility",
                    "requirements": [
                        {
                            "requirement_type": "accessibility",
                            "expected_value": "easily accessible"
                        }
                    ]
                },
                {
                    "exact_snippets": "must have overexpression of eIF4E in the metastatic tissue",
                    "criterion": "eIF4E overexpression in metastatic tissue",
                    "requirements": [
                        {
                            "requirement_type": "overexpression",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Easily accessible lesion for serial biopsies (ex. skin, superficial lymph node, or other easily accessible site).",
            "criterions": [
                {
                    "exact_snippets": "Easily accessible lesion",
                    "criterion": "lesion accessibility",
                    "requirements": [
                        {
                            "requirement_type": "accessibility",
                            "expected_value": "easily accessible"
                        }
                    ]
                },
                {
                    "exact_snippets": "serial biopsies",
                    "criterion": "lesion suitability for serial biopsies",
                    "requirements": [
                        {
                            "requirement_type": "suitability",
                            "expected_value": "suitable for serial biopsies"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* At least 1 unidimensionally measurable lesion (based on the RECIST criteria) outside the CNS.",
            "criterions": [
                {
                    "exact_snippets": "At least 1 unidimensionally measurable lesion ... outside the CNS.",
                    "criterion": "unidimensionally measurable lesion",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "N/A"
                            }
                        },
                        {
                            "requirement_type": "location",
                            "expected_value": "outside the CNS"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* ECOG 0, 1, or 2.",
            "criterions": [
                {
                    "exact_snippets": "ECOG 0, 1, or 2.",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": [
                                "0",
                                "1",
                                "2"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate recovery (excluding alopecia) from previous surgery, radiation, and chemotherapy.",
            "criterions": [
                {
                    "exact_snippets": "Adequate recovery ... from previous surgery",
                    "criterion": "recovery from previous surgery",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate recovery ... from previous ... radiation",
                    "criterion": "recovery from previous radiation",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate recovery ... from previous ... chemotherapy",
                    "criterion": "recovery from previous chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate wash-out period from last therapy for breast cancer (at least 3 weeks).",
            "criterions": [
                {
                    "exact_snippets": "Adequate wash-out period from last therapy for breast cancer (at least 3 weeks)",
                    "criterion": "wash-out period from last therapy for breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Life expectancy ≥ 12 weeks.",
            "criterions": [
                {
                    "exact_snippets": "Life expectancy ≥ 12 weeks.",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Age is ≥ 18 years. There is no upper age limit since the drug can be administered orally and even considered in a palliative setting.",
            "criterions": [
                {
                    "exact_snippets": "Age is ≥ 18 years.",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Female patients of childbearing potential must have a negative serum (beta-HCG) pregnancy test within 14 days of starting protocol and must not be breastfeeding. Men and women of childbearing potential must agree to use an effective means of contraception throughout the study and for at least 6 months after completion of protocol. Post-menopausal women (defined as 12 or more consecutive months of amenorrhea, or follicle stimulating hormone (FSH) in the post-menopausal range), or surgically sterile women, do not require methods of contraception.",
            "criterions": [
                {
                    "exact_snippets": "Female patients of childbearing potential",
                    "criterion": "female patients of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "pregnancy test",
                            "expected_value": "negative serum (beta-HCG) pregnancy test within 14 days of starting protocol"
                        }
                    ]
                },
                {
                    "exact_snippets": "Female patients of childbearing potential ... must not be breastfeeding",
                    "criterion": "breastfeeding status",
                    "requirements": [
                        {
                            "requirement_type": "breastfeeding",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Men and women of childbearing potential must agree to use an effective means of contraception throughout the study and for at least 6 months after completion of protocol",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": "use an effective means of contraception throughout the study and for at least 6 months after completion of protocol"
                        }
                    ]
                },
                {
                    "exact_snippets": "Post-menopausal women (defined as 12 or more consecutive months of amenorrhea, or follicle stimulating hormone (FSH) in the post-menopausal range)",
                    "criterion": "post-menopausal status",
                    "requirements": [
                        {
                            "requirement_type": "definition",
                            "expected_value": [
                                "12 or more consecutive months of amenorrhea",
                                "follicle stimulating hormone (FSH) in the post-menopausal range"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "surgically sterile women",
                    "criterion": "surgical sterility",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate renal and hepatic function: serum creatinine < 1.5 x ULN; AST or ALT < 2.5 x ULN (or < 5 x ULN if liver involvement with metastases); serum bilirubin < 1.5 x ULN.",
            "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": "AST or ALT < 2.5 x ULN (or < 5 x ULN if liver involvement with metastases)",
                    "criterion": "AST or ALT",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<",
                                        "value": 2.5,
                                        "unit": "x ULN"
                                    },
                                    {
                                        "operator": "<",
                                        "value": 5,
                                        "unit": "x ULN"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "serum bilirubin < 1.5 x ULN",
                    "criterion": "serum bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 1.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate hematopoietic function: neutrophils ≥1.0 x 10E9/L, platelets ≥ 100 x 10E9/L.",
            "criterions": [
                {
                    "exact_snippets": "Adequate hematopoietic function: neutrophils ≥1.0 x 10E9/L",
                    "criterion": "neutrophils",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.0,
                                "unit": "x 10E9/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate hematopoietic function: ... platelets ≥ 100 x 10E9/L",
                    "criterion": "platelets",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100,
                                "unit": "x 10E9/L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Provide written consent after the investigational nature, study design, risks and benefits of the study have been explained.",
            "criterions": [
                {
                    "exact_snippets": "Provide written consent",
                    "criterion": "written consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Accessible for treatment and follow up.",
            "criterions": [
                {
                    "exact_snippets": "Accessible for treatment",
                    "criterion": "accessibility for treatment",
                    "requirements": [
                        {
                            "requirement_type": "accessibility",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Accessible for ... follow up",
                    "criterion": "accessibility for follow up",
                    "requirements": [
                        {
                            "requirement_type": "accessibility",
                            "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": "* Symptomatic brain metastases.",
            "criterions": [
                {
                    "exact_snippets": "Symptomatic brain metastases.",
                    "criterion": "brain metastases",
                    "requirements": [
                        {
                            "requirement_type": "symptomatic",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Active cardiovascular disease as defined by New York Heart Association (NYHA) class III-IV categorization.",
            "criterions": [
                {
                    "exact_snippets": "Active cardiovascular disease as defined by New York Heart Association (NYHA) class III-IV categorization",
                    "criterion": "cardiovascular disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 3,
                                        "unit": "NYHA class"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Intercurrent illness or medical condition precluding safe administration of the planned protocol treatment or required follow-up.",
            "criterions": [
                {
                    "exact_snippets": "Intercurrent illness or medical condition precluding safe administration of the planned protocol treatment",
                    "criterion": "intercurrent illness or medical condition",
                    "requirements": [
                        {
                            "requirement_type": "impact on treatment",
                            "expected_value": "precludes safe administration of the planned protocol treatment"
                        }
                    ]
                },
                {
                    "exact_snippets": "Intercurrent illness or medical condition ... precluding safe administration of ... required follow-up",
                    "criterion": "intercurrent illness or medical condition",
                    "requirements": [
                        {
                            "requirement_type": "impact on follow-up",
                            "expected_value": "precludes safe administration of required follow-up"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Use of any investigational drug within 4 weeks before start of study treatment or inadequate recovery from any toxic effects of such therapy.",
            "criterions": [
                {
                    "exact_snippets": "Use of any investigational drug within 4 weeks before start of study treatment",
                    "criterion": "use of investigational drug",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "inadequate recovery from any toxic effects of such therapy",
                    "criterion": "recovery from toxic effects",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": "inadequate"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Female patients who are pregnant or breastfeeding.",
            "criterions": [
                {
                    "exact_snippets": "Female patients",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "expected_value",
                            "expected_value": "female"
                        }
                    ]
                },
                {
                    "exact_snippets": "pregnant",
                    "criterion": "pregnancy status",
                    "requirements": [
                        {
                            "requirement_type": "expected_value",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "breastfeeding",
                    "criterion": "breastfeeding status",
                    "requirements": [
                        {
                            "requirement_type": "expected_value",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Concurrent treatment with other anti-cancer therapy. Bisphosphonates are allowed as long as they were started prior to screening (at least 4 weeks before study entry) and the dose does not change during study participation.",
            "criterions": [
                {
                    "exact_snippets": "Concurrent treatment with other anti-cancer therapy.",
                    "criterion": "concurrent anti-cancer therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Bisphosphonates are allowed ... started prior to screening (at least 4 weeks before study entry)",
                    "criterion": "bisphosphonate treatment",
                    "requirements": [
                        {
                            "requirement_type": "start time",
                            "expected_value": {
                                "operator": "<=",
                                "value": -4,
                                "unit": "weeks before study entry"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Bisphosphonates are allowed ... the dose does not change during study participation.",
                    "criterion": "bisphosphonate dose change",
                    "requirements": [
                        {
                            "requirement_type": "change",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Known infection with HIV.",
            "criterions": [
                {
                    "exact_snippets": "Known infection with HIV",
                    "criterion": "HIV infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of other malignancy in the past 5 years. Subjects who have been disease-free for 1 year or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.",
            "criterions": [
                {
                    "exact_snippets": "History of other malignancy in the past 5 years",
                    "criterion": "history of other malignancy",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 5,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Subjects who have been disease-free for 1 year",
                    "criterion": "disease-free status",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "year"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "subjects with a history of completely resected non-melanoma skin cancer",
                    "criterion": "history of completely resected non-melanoma skin cancer",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "completely resected"
                        }
                    ]
                },
                {
                    "exact_snippets": "successfully treated in situ carcinoma",
                    "criterion": "in situ carcinoma",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "successfully treated"
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}