{
    "info": {
        "nct_id": "NCT01097460",
        "official_title": "MM-111-02-12-02: A Phase 1 Study of MM-111 in Combination With Herceptin in Patients With Advanced, Refractory Her2 Amplified, Heregulin Positive Breast Cancer",
        "inclusion_criteria": "* Patients must have histologically or cytologically confirmed advanced breast cancer that is amplified for HER2, based on archived tumor biopsy (IHC 2+ or greater)\n* Patients must have histologically or cytologically confirmed advanced breast cancer that is heregulin positive based on fresh tumor tissue biopsy\n* The patient's cancer must have recurred, progressed or not responded to standard chemotherapy or other standard treatment. Prior therapies may include but are not limited to Herceptin, Tykerb (lapatinib), anthracyclines, and taxanes\n* Patients must be ≥ 18 years of age\n* Patients or their legal representatives must be able to understand and sign an informed consent\n* Patients may have measurable (per RECIST 1.1) or non-measurable tumor(s) (for Phase 1)\n* Patients should have ECOG Performance Score (PS) 0, 1 or 2 (for Phase 1).\n* Patients should have a life expectancy of at least 12 weeks\n* Patients must have adequate bone marrow reserves\n* Patients must have adequate hepatic function\n* Patients must have adequate renal function\n* Patients must be recovered from the effects of any prior surgery, radiotherapy or other antineoplastic therapy.\n* Women of childbearing potential as well as fertile men and their partners must agree to abstain from sexual intercourse or to use an effective form of contraception during the study and for 90 days following the last dose of MM-111.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Patients who are pregnant or lactating\n* Patients with an active infection or with an unexplained fever > 38.5°C (101.3° F) during screening visits or on the first scheduled day of dosing.\n* Patients with untreated and/or symptomatic metastatic CNS malignancies.\n* Patients with known hypersensitivity to any of the components of MM-111 or who have had hypersensitivity reactions to fully human monoclonal antibodies, including Herceptin.\n* Patients who have received other recent antitumor therapy including:\n\n  * Treatment with Herceptin within the 28 days prior to the first scheduled day of dosing with MM-111\n  * Investigational therapy administered within the 28 days prior to the first scheduled day of dosing MM-111 (Dosing in less than 28 days' since receiving investigational therapy is acceptable once a time interval equal to at least five half-lives of the investigational agent has passed.)\n  * Any standard chemotherapy, Tykerb (lapatinib) or radiation within 14 days (and having passed the time of any actual or anticipated toxicities) prior to the first scheduled dose of MM-111\n* Patients who have previously received MM-111\n* Patients with NYHA Class III or IV congestive heart failure or LVEF < 50%\n* Patients with a history of allogeneic transplant\n* Patients with known HIV, hepatitis B or C (if patients have previously been treated for hepatitis C and have undetectable viral loads, they can be considered eligible for the trial)\n* Patients with any other medical or psychological condition deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Patients must have histologically or cytologically confirmed advanced breast cancer that is amplified for HER2, based on archived tumor biopsy (IHC 2+ or greater)",
            "criterions": [
                {
                    "exact_snippets": "histologically or cytologically confirmed advanced breast cancer",
                    "criterion": "advanced breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": [
                                "histologically",
                                "cytologically"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "amplified for HER2",
                    "criterion": "HER2 amplification",
                    "requirements": [
                        {
                            "requirement_type": "amplification",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "based on archived tumor biopsy",
                    "criterion": "archived tumor biopsy",
                    "requirements": [
                        {
                            "requirement_type": "source",
                            "expected_value": "archived tumor biopsy"
                        }
                    ]
                },
                {
                    "exact_snippets": "IHC 2+ or greater",
                    "criterion": "IHC score",
                    "requirements": [
                        {
                            "requirement_type": "score",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "+"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must have histologically or cytologically confirmed advanced breast cancer that is heregulin positive based on fresh tumor tissue biopsy",
            "criterions": [
                {
                    "exact_snippets": "histologically or cytologically confirmed advanced breast cancer",
                    "criterion": "advanced breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": [
                                "histologically",
                                "cytologically"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "heregulin positive",
                    "criterion": "heregulin status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "positive"
                        }
                    ]
                },
                {
                    "exact_snippets": "fresh tumor tissue biopsy",
                    "criterion": "tumor tissue biopsy",
                    "requirements": [
                        {
                            "requirement_type": "freshness",
                            "expected_value": "fresh"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* The patient's cancer must have recurred, progressed or not responded to standard chemotherapy or other standard treatment. Prior therapies may include but are not limited to Herceptin, Tykerb (lapatinib), anthracyclines, and taxanes",
            "criterions": [
                {
                    "exact_snippets": "cancer must have recurred",
                    "criterion": "cancer recurrence",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "cancer must have ... progressed",
                    "criterion": "cancer progression",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "cancer must have ... not responded to standard chemotherapy or other standard treatment",
                    "criterion": "response to standard treatment",
                    "requirements": [
                        {
                            "requirement_type": "response",
                            "expected_value": "not responded"
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior therapies may include ... Herceptin, Tykerb (lapatinib), anthracyclines, and taxanes",
                    "criterion": "prior therapies",
                    "requirements": [
                        {
                            "requirement_type": "inclusion",
                            "expected_value": [
                                "Herceptin",
                                "Tykerb (lapatinib)",
                                "anthracyclines",
                                "taxanes"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must be ≥ 18 years of age",
            "criterions": [
                {
                    "exact_snippets": "Patients must be ≥ 18 years of age",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients or their legal representatives must be able to understand and sign an informed consent",
            "criterions": [
                {
                    "exact_snippets": "Patients or their legal representatives must be able to understand",
                    "criterion": "understanding",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "sign an informed consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients may have measurable (per RECIST 1.1) or non-measurable tumor(s) (for Phase 1)",
            "criterions": [
                {
                    "exact_snippets": "measurable (per RECIST 1.1)",
                    "criterion": "tumor measurability",
                    "requirements": [
                        {
                            "requirement_type": "measurability",
                            "expected_value": "measurable per RECIST 1.1"
                        }
                    ]
                },
                {
                    "exact_snippets": "non-measurable tumor(s) (for Phase 1)",
                    "criterion": "tumor measurability",
                    "requirements": [
                        {
                            "requirement_type": "measurability",
                            "expected_value": "non-measurable for Phase 1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients should have ECOG Performance Score (PS) 0, 1 or 2 (for Phase 1).",
            "criterions": [
                {
                    "exact_snippets": "ECOG Performance Score (PS) 0, 1 or 2",
                    "criterion": "ECOG Performance Score",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": [
                                "0",
                                "1",
                                "2"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients should have a life expectancy of at least 12 weeks",
            "criterions": [
                {
                    "exact_snippets": "life expectancy of at least 12 weeks",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 12,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must have adequate bone marrow reserves",
            "criterions": [
                {
                    "exact_snippets": "adequate bone marrow reserves",
                    "criterion": "bone marrow reserves",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must have adequate hepatic function",
            "criterions": [
                {
                    "exact_snippets": "adequate hepatic function",
                    "criterion": "hepatic function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must have adequate renal function",
            "criterions": [
                {
                    "exact_snippets": "adequate renal function",
                    "criterion": "renal function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must be recovered from the effects of any prior surgery, radiotherapy or other antineoplastic therapy.",
            "criterions": [
                {
                    "exact_snippets": "recovered from the effects of any prior surgery",
                    "criterion": "recovery from prior surgery",
                    "requirements": [
                        {
                            "requirement_type": "recovery",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "recovered from the effects of any prior ... radiotherapy",
                    "criterion": "recovery from prior radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "recovery",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "recovered from the effects of any prior ... other antineoplastic therapy",
                    "criterion": "recovery from prior antineoplastic therapy",
                    "requirements": [
                        {
                            "requirement_type": "recovery",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Women of childbearing potential as well as fertile men and their partners must agree to abstain from sexual intercourse or to use an effective form of contraception during the study and for 90 days following the last dose of MM-111.",
            "criterions": [
                {
                    "exact_snippets": "Women of childbearing potential",
                    "criterion": "women of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": "abstain from sexual intercourse or to use an effective form of contraception during the study and for 90 days following the last dose of MM-111"
                        }
                    ]
                },
                {
                    "exact_snippets": "fertile men and their partners",
                    "criterion": "fertile men and their partners",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": "abstain from sexual intercourse or to use an effective form of contraception during the study and for 90 days following the last dose of MM-111"
                        }
                    ]
                }
            ]
        },
        {
            "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": "* Patients who are pregnant or lactating",
            "criterions": [
                {
                    "exact_snippets": "Patients who are pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients who are ... lactating",
                    "criterion": "lactation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with an active infection or with an unexplained fever > 38.5°C (101.3° F) during screening visits or on the first scheduled day of dosing.",
            "criterions": [
                {
                    "exact_snippets": "Patients with an active infection",
                    "criterion": "active infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "unexplained fever > 38.5°C (101.3° F)",
                    "criterion": "unexplained fever",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">",
                                "value": 38.5,
                                "unit": "°C"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with untreated and/or symptomatic metastatic CNS malignancies.",
            "criterions": [
                {
                    "exact_snippets": "untreated ... metastatic CNS malignancies",
                    "criterion": "metastatic CNS malignancies",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "untreated"
                        }
                    ]
                },
                {
                    "exact_snippets": "symptomatic metastatic CNS malignancies",
                    "criterion": "metastatic CNS malignancies",
                    "requirements": [
                        {
                            "requirement_type": "symptom presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with known hypersensitivity to any of the components of MM-111 or who have had hypersensitivity reactions to fully human monoclonal antibodies, including Herceptin.",
            "criterions": [
                {
                    "exact_snippets": "known hypersensitivity to any of the components of MM-111",
                    "criterion": "hypersensitivity to MM-111 components",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "hypersensitivity reactions to fully human monoclonal antibodies, including Herceptin",
                    "criterion": "hypersensitivity to fully human monoclonal antibodies",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who have received other recent antitumor therapy including:",
            "criterions": [
                {
                    "exact_snippets": "Patients who have received other recent antitumor therapy",
                    "criterion": "recent antitumor therapy",
                    "requirements": [
                        {
                            "requirement_type": "receipt",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Treatment with Herceptin within the 28 days prior to the first scheduled day of dosing with MM-111",
            "criterions": [
                {
                    "exact_snippets": "Treatment with Herceptin within the 28 days prior to the first scheduled day of dosing with MM-111",
                    "criterion": "Herceptin treatment",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Investigational therapy administered within the 28 days prior to the first scheduled day of dosing MM-111 (Dosing in less than 28 days' since receiving investigational therapy is acceptable once a time interval equal to at least five half-lives of the investigational agent has passed.)",
            "criterions": [
                {
                    "exact_snippets": "Investigational therapy administered within the 28 days prior to the first scheduled day of dosing MM-111",
                    "criterion": "investigational therapy administration",
                    "requirements": [
                        {
                            "requirement_type": "time since administration",
                            "expected_value": {
                                "operator": "<",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Dosing in less than 28 days' since receiving investigational therapy is acceptable once a time interval equal to at least five half-lives of the investigational agent has passed",
                    "criterion": "time interval since investigational therapy",
                    "requirements": [
                        {
                            "requirement_type": "time interval",
                            "expected_value": {
                                "operator": ">=",
                                "value": 5,
                                "unit": "half-lives"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any standard chemotherapy, Tykerb (lapatinib) or radiation within 14 days (and having passed the time of any actual or anticipated toxicities) prior to the first scheduled dose of MM-111",
            "criterions": [
                {
                    "exact_snippets": "Any standard chemotherapy ... within 14 days",
                    "criterion": "standard chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": ">=",
                                "value": 14,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Tykerb (lapatinib) ... within 14 days",
                    "criterion": "Tykerb (lapatinib)",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": ">=",
                                "value": 14,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "radiation within 14 days",
                    "criterion": "radiation",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": ">=",
                                "value": 14,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "having passed the time of any actual or anticipated toxicities",
                    "criterion": "toxicities",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "resolved"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who have previously received MM-111",
            "criterions": [
                {
                    "exact_snippets": "Patients who have previously received MM-111",
                    "criterion": "previous MM-111 treatment",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with NYHA Class III or IV congestive heart failure or LVEF < 50%",
            "criterions": [
                {
                    "exact_snippets": "NYHA Class III or IV congestive heart failure",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "NYHA Class III",
                                "NYHA Class IV"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "LVEF < 50%",
                    "criterion": "left ventricular ejection fraction (LVEF)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<",
                                "value": 50,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with a history of allogeneic transplant",
            "criterions": [
                {
                    "exact_snippets": "history of allogeneic transplant",
                    "criterion": "allogeneic transplant",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with known HIV, hepatitis B or C (if patients have previously been treated for hepatitis C and have undetectable viral loads, they can be considered eligible for the trial)",
            "criterions": [
                {
                    "exact_snippets": "known HIV",
                    "criterion": "HIV",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "hepatitis B",
                    "criterion": "hepatitis B",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "hepatitis C",
                    "criterion": "hepatitis C",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "previously been treated for hepatitis C ... undetectable viral loads",
                    "criterion": "hepatitis C viral load",
                    "requirements": [
                        {
                            "requirement_type": "detectability",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with any other medical or psychological condition deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results",
            "criterions": [
                {
                    "exact_snippets": "any other medical or psychological condition",
                    "criterion": "medical or psychological condition",
                    "requirements": [
                        {
                            "requirement_type": "interference with ability to sign informed consent",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "interference with ability to cooperate and participate in the study",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "interference with interpretation of the results",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}