{
    "info": {
        "nct_id": "NCT01526473",
        "official_title": "A Phase I Study To Evaluate The Antitumor Activity And Safety Of DUKE-002-VRP(HUHER2-ECD+TM), An Alphaviral Vector Encoding The HER2 Extracellular Domain And Transmembrane Region, In Patient With Locally Advanced Or Metastatic Human Epidermal Growth Factor Receptor 2-Positive (HER2+) Cancers Including Breast Cancer",
        "inclusion_criteria": "Healthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "",
        "miscellaneous_criteria": "Inclusion criteria\n\n* One of the following subgroups of patients with HER2 overexpression as follows:\n\n  (i) Histologically-confirmed breast cancer that is metastatic or locally recurrent (7th Edition of the AJCC TNM System) and measurable and/or evaluable or non-measurable by RECIST 1.1 criteria with HER2/neu overexpression by immunohistochemistry (2+,3+) or FISH+ and progressive disease despite having received at least 1 prior FDA approved HER2 targeted (e.g. trastuzumab, trastuzumab plus pertuzumab, T-DM1, or lapatinib) (determined by their physician).*\n\n  *Prior therapy has at least one of the following stipulations:\n* Patients may have received neoadjuvant or adjuvant treatment with prior trastuzumab or lapatinib treatment\n* Patients have received a a trastuzumab, trastuzumab + pertuzumab, or T-DM1-based therapy for locally advanced or metastatic disease for a minimum of 9 weeks duration. Patients may have received more than 1 trastuzumab-based combination therapy.\n* Patients have received a lapatinib-based therapy for locally advanced or metastatic disease for a minimum of 9 weeks duration. Patients may have received more than 1 lapatinib-based combination therapy.\n\n(ii) Histologically-confirmed gastric, esophageal, or gastroesophageal adenocarcinoma that is metastatic or locally recurrent (7th Edition of the AJCC TNM System) and measurable or non-measurable by RECIST 1.1 criteria with HER2/neu overexpression by immunohistochemistry (2+,3+) or FISH+ and progressive disease despite having received at least 1 prior HER2 targeted therapy for a minimum of 9 weeks duration) (determined by their physician). or with previously documented HER2 over-expressing disease not being currently treated on a HER2 targeted therapy.\n\n(iii) Other histologically confirmed metastatic (stage IV) or locally recurrent (stage III) (7th Edition of the AJCC TNM System) malignancy with HER2/neu overexpression by immunohistochemistry (2+,3+) or FISH+. Because there are no other malignancies with FDA approved HER2 targeting therapies, no prior HER2 directed therapy will be required for this subgroup. However, patients will have been required to have at least 1 line of therapy with a known survival benefit for their malignancy.\n\n* Adults at least 18 years of age at the time of signing the Informed Consent Form;\n* Written informed consent obtained from the patient prior to performing any study-related procedures, including screening visits. however, CT scans, bone scans, MUGA, Echocardiogram, EKG,and labs performed as standard of care prior to signing consent can be used to fulfill eligibility requirements if they were performed within 8 weeks of the first dose of AVX901 (for the MUGA or echocardiogram) and within 4 weeksof the first dose of study drug for the remainder of the studies\n* Resolution of all toxic side effects of prior chemotherapy, radiotherapy or surgical procedures to NCI CTCAE (version 4.03) Grade ≤ 1 (with the exception of grade 2 alopecia, grade 2 neuropathy and grade 2 fatigue);\n* Karnofsky performance status greater than or equal to 80% or ECOG status of 0 or 1 ;\n* Adequate hematologic function: (WBC = 2500 mm3, hemoglobin > 10 mg/dl, platelets > 100,000/mm3);\n* Adequate renal and hepatic function (Cr < 2.0 mg/dl; bilirubin < 2 X ULN; AST < 2.5 x ULN, ALT < 2.5 X ULN);\n* Normal cardiac function defined as either a MUGA or ECHO with LVEF in normal institutional range (MUGA 50%; ECHO 55%);\n* Female patients must be of non child-bearing potential or use effective contraception, e.g., use of oral contraceptives with an additional barrier method (since the study drug may impair the effectiveness of oral contraceptives), double barrier methods (diaphragm with spermicidal gel or condoms with contraceptive foam), Depo-Provera, partner vasectomy, total abstinence, and willing to continue the effective contraception method for 30 days after the last dose of AVX901;\n* Ability to return to Duke University Medical Center for adequate follow-up as required by this protocol;\n* Current therapy with endocrine agents (tamoxifen, raloxifene, torimifene and all aromatase inhibitors) and/or bisphosphonates and/or RANK-ligand inhibitors is permitted.\n\nExclusion criteria\n\n* Except for patients on the concurrent HER2 targeted therapy (cohort 2) cohort, patients may not receive cytotoxic chemotherapy, monoclonal antibodies (other than RANK-ligand inhibitors being used for bone protection), HER2 targeted therapy such as lapatinib, or radiation therapy in the 3 weeks before the first injection, during the injection period or for at least 2 weeks after the last injection. Patients may have received prior radiation including for brain metastases.\n* History of auto-immune disease such as, but not restricted to, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis. Prior history of autoimmune thyroiditis or vitiligo is permitted.\n* Serious chronic or acute illness considered by the P.I. to constitute an unwarranted high risk for investigational drug treatment.\n* Medical or psychological impediment to probable compliance with the protocol.\n* Concurrent or prior second malignancy (within the past 5 years) other than non-melanoma skin cancer, controlled superficial bladder cancer or controlled cervical cancer.\n* Presence of active infection or systemic use of antimicrobials within 72 hours prior to the first injection\n* Patients on steroid therapy (or other immunosuppressives such as azathioprine or cyclosporine A) are excluded on the basis of potential immune suppression. Patients must have had 6 weeks of discontinuation of any steroid therapy prior to enrollment (except steroids used as anti-emetics for systemic chemotherapy which are permitted).\n* Presence of an active acute or chronic infection including HIV (as determined by ELISA and confirmed by Western Blot) or viral hepatitis (as determined by HBsAg and Hepatitis C serology). Patients with HIV are excluded based on immuno-suppression, which may render them unable to respond to the vaccine; patients with chronic hepatitis are excluded because of concern that hepatitis could be exacerbated by the injections. .\n* Pregnant or nursing women"
    },
    "inclusion_lines": [
        {
            "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": [
        {
            "line": "* One of the following subgroups of patients with HER2 overexpression as follows:",
            "criterions": [
                {
                    "exact_snippets": "HER2 overexpression",
                    "criterion": "HER2 overexpression",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "(i) Histologically-confirmed breast cancer that is metastatic or locally recurrent (7th Edition of the AJCC TNM System) and measurable and/or evaluable or non-measurable by RECIST 1.1 criteria with HER2/neu overexpression by immunohistochemistry (2+,3+) or FISH+ and progressive disease despite having received at least 1 prior FDA approved HER2 targeted (e.g. trastuzumab, trastuzumab plus pertuzumab, T-DM1, or lapatinib) (determined by their physician).*",
            "criterions": [
                {
                    "exact_snippets": "Histologically-confirmed breast cancer",
                    "criterion": "breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": "histologically-confirmed"
                        }
                    ]
                },
                {
                    "exact_snippets": "metastatic or locally recurrent",
                    "criterion": "cancer stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "metastatic",
                                "locally recurrent"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "measurable and/or evaluable or non-measurable by RECIST 1.1 criteria",
                    "criterion": "tumor measurability",
                    "requirements": [
                        {
                            "requirement_type": "criteria",
                            "expected_value": "RECIST 1.1"
                        }
                    ]
                },
                {
                    "exact_snippets": "HER2/neu overexpression by immunohistochemistry (2+,3+) or FISH+",
                    "criterion": "HER2/neu overexpression",
                    "requirements": [
                        {
                            "requirement_type": "detection method",
                            "expected_value": [
                                "immunohistochemistry (2+,3+)",
                                "FISH+"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "progressive disease despite having received at least 1 prior FDA approved HER2 targeted",
                    "criterion": "treatment history",
                    "requirements": [
                        {
                            "requirement_type": "prior treatment",
                            "expected_value": "at least 1 prior FDA approved HER2 targeted"
                        }
                    ]
                }
            ]
        },
        {
            "line": "*Prior therapy has at least one of the following stipulations:",
            "criterions": [
                {
                    "exact_snippets": "Prior therapy has at least one of the following stipulations",
                    "criterion": "prior therapy",
                    "requirements": [
                        {
                            "requirement_type": "stipulations",
                            "expected_value": "at least one"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients may have received neoadjuvant or adjuvant treatment with prior trastuzumab or lapatinib treatment",
            "criterions": [
                {
                    "exact_snippets": "Patients may have received neoadjuvant or adjuvant treatment",
                    "criterion": "neoadjuvant or adjuvant treatment",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "prior trastuzumab or lapatinib treatment",
                    "criterion": "trastuzumab or lapatinib treatment",
                    "requirements": [
                        {
                            "requirement_type": "prior treatment",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients have received a lapatinib-based therapy for locally advanced or metastatic disease for a minimum of 9 weeks duration. Patients may have received more than 1 lapatinib-based combination therapy.",
            "criterions": [
                {
                    "exact_snippets": "Patients have received a lapatinib-based therapy",
                    "criterion": "lapatinib-based therapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "for locally advanced or metastatic disease",
                    "criterion": "disease stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "locally advanced",
                                "metastatic"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "for a minimum of 9 weeks duration",
                    "criterion": "therapy duration",
                    "requirements": [
                        {
                            "requirement_type": "minimum duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 9,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients may have received more than 1 lapatinib-based combination therapy",
                    "criterion": "lapatinib-based combination therapy",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">",
                                "value": 1,
                                "unit": "therapy"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "(ii) Histologically-confirmed gastric, esophageal, or gastroesophageal adenocarcinoma that is metastatic or locally recurrent (7th Edition of the AJCC TNM System) and measurable or non-measurable by RECIST 1.1 criteria with HER2/neu overexpression by immunohistochemistry (2+,3+) or FISH+ and progressive disease despite having received at least 1 prior HER2 targeted therapy for a minimum of 9 weeks duration) (determined by their physician). or with previously documented HER2 over-expressing disease not being currently treated on a HER2 targeted therapy.",
            "criterions": [
                {
                    "exact_snippets": "Histologically-confirmed gastric, esophageal, or gastroesophageal adenocarcinoma",
                    "criterion": "adenocarcinoma type",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "gastric",
                                "esophageal",
                                "gastroesophageal"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "metastatic or locally recurrent",
                    "criterion": "cancer stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "metastatic",
                                "locally recurrent"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "measurable or non-measurable by RECIST 1.1 criteria",
                    "criterion": "tumor measurability",
                    "requirements": [
                        {
                            "requirement_type": "measurability",
                            "expected_value": [
                                "measurable",
                                "non-measurable"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "HER2/neu overexpression by immunohistochemistry (2+,3+) or FISH+",
                    "criterion": "HER2/neu overexpression",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": [
                                "immunohistochemistry (2+,3+)",
                                "FISH+"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "progressive disease despite having received at least 1 prior HER2 targeted therapy for a minimum of 9 weeks duration",
                    "criterion": "HER2 targeted therapy",
                    "requirements": [
                        {
                            "requirement_type": "prior therapy",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 9,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "previously documented HER2 over-expressing disease not being currently treated on a HER2 targeted therapy",
                    "criterion": "current HER2 targeted therapy",
                    "requirements": [
                        {
                            "requirement_type": "current therapy",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "(iii) Other histologically confirmed metastatic (stage IV) or locally recurrent (stage III) (7th Edition of the AJCC TNM System) malignancy with HER2/neu overexpression by immunohistochemistry (2+,3+) or FISH+. Because there are no other malignancies with FDA approved HER2 targeting therapies, no prior HER2 directed therapy will be required for this subgroup. However, patients will have been required to have at least 1 line of therapy with a known survival benefit for their malignancy.",
            "criterions": [
                {
                    "exact_snippets": "Other histologically confirmed metastatic (stage IV) or locally recurrent (stage III) (7th Edition of the AJCC TNM System) malignancy",
                    "criterion": "malignancy stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "stage IV",
                                "stage III"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "HER2/neu overexpression by immunohistochemistry (2+,3+) or FISH+",
                    "criterion": "HER2/neu overexpression",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": [
                                "immunohistochemistry",
                                "FISH"
                            ]
                        },
                        {
                            "requirement_type": "level",
                            "expected_value": [
                                "2+",
                                "3+",
                                "FISH+"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "at least 1 line of therapy with a known survival benefit for their malignancy",
                    "criterion": "prior therapy",
                    "requirements": [
                        {
                            "requirement_type": "minimum lines",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "lines"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adults at least 18 years of age at the time of signing the Informed Consent Form;",
            "criterions": [
                {
                    "exact_snippets": "Adults at least 18 years of age",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Resolution of all toxic side effects of prior chemotherapy, radiotherapy or surgical procedures to NCI CTCAE (version 4.03) Grade ≤ 1 (with the exception of grade 2 alopecia, grade 2 neuropathy and grade 2 fatigue);",
            "criterions": [
                {
                    "exact_snippets": "Resolution of all toxic side effects of prior chemotherapy, radiotherapy or surgical procedures to NCI CTCAE (version 4.03) Grade ≤ 1",
                    "criterion": "toxic side effects of prior chemotherapy, radiotherapy or surgical procedures",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 1,
                                        "unit": "NCI CTCAE (version 4.03) Grade"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "(with the exception of grade 2 alopecia",
                    "criterion": "alopecia",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "=",
                                        "value": 2,
                                        "unit": "grade"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "(with the exception of ... grade 2 neuropathy",
                    "criterion": "neuropathy",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "=",
                                        "value": 2,
                                        "unit": "grade"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "(with the exception of ... grade 2 fatigue",
                    "criterion": "fatigue",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "=",
                                        "value": 2,
                                        "unit": "grade"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Karnofsky performance status greater than or equal to 80% or ECOG status of 0 or 1 ;",
            "criterions": [
                {
                    "exact_snippets": "Karnofsky performance status greater than or equal to 80%",
                    "criterion": "Karnofsky performance status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 80,
                                "unit": "%"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "ECOG status of 0 or 1",
                    "criterion": "ECOG status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": [
                                "0",
                                "1"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate hematologic function: (WBC = 2500 mm3, hemoglobin > 10 mg/dl, platelets > 100,000/mm3);",
            "criterions": [
                {
                    "exact_snippets": "Adequate hematologic function: (WBC = 2500 mm3",
                    "criterion": "white blood cell count (WBC)",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "=",
                                "value": 2500,
                                "unit": "mm3"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate hematologic function: ... hemoglobin > 10 mg/dl",
                    "criterion": "hemoglobin level",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">",
                                "value": 10,
                                "unit": "mg/dl"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate hematologic function: ... platelets > 100,000/mm3",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">",
                                "value": 100000,
                                "unit": "mm3"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate renal and hepatic function (Cr < 2.0 mg/dl; bilirubin < 2 X ULN; AST < 2.5 x ULN, ALT < 2.5 X ULN);",
            "criterions": [
                {
                    "exact_snippets": "Adequate renal ... Cr < 2.0 mg/dl",
                    "criterion": "renal function",
                    "requirements": [
                        {
                            "requirement_type": "creatinine level",
                            "expected_value": {
                                "operator": "<",
                                "value": 2.0,
                                "unit": "mg/dl"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate ... hepatic function ... bilirubin < 2 X ULN",
                    "criterion": "hepatic function",
                    "requirements": [
                        {
                            "requirement_type": "bilirubin level",
                            "expected_value": {
                                "operator": "<",
                                "value": 2,
                                "unit": "X ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate ... hepatic function ... AST < 2.5 x ULN",
                    "criterion": "hepatic function",
                    "requirements": [
                        {
                            "requirement_type": "AST level",
                            "expected_value": {
                                "operator": "<",
                                "value": 2.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate ... hepatic function ... ALT < 2.5 X ULN",
                    "criterion": "hepatic function",
                    "requirements": [
                        {
                            "requirement_type": "ALT level",
                            "expected_value": {
                                "operator": "<",
                                "value": 2.5,
                                "unit": "X ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Normal cardiac function defined as either a MUGA or ECHO with LVEF in normal institutional range (MUGA 50%; ECHO 55%);",
            "criterions": [
                {
                    "exact_snippets": "Normal cardiac function defined as either a MUGA or ECHO with LVEF in normal institutional range",
                    "criterion": "cardiac function",
                    "requirements": [
                        {
                            "requirement_type": "method",
                            "expected_value": [
                                "MUGA",
                                "ECHO"
                            ]
                        },
                        {
                            "requirement_type": "LVEF",
                            "expected_value": "normal institutional range"
                        }
                    ]
                },
                {
                    "exact_snippets": "MUGA 50%",
                    "criterion": "LVEF (MUGA)",
                    "requirements": [
                        {
                            "requirement_type": "minimum value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 50,
                                "unit": "%"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "ECHO 55%",
                    "criterion": "LVEF (ECHO)",
                    "requirements": [
                        {
                            "requirement_type": "minimum value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 55,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Female patients must be of non child-bearing potential or use effective contraception, e.g., use of oral contraceptives with an additional barrier method (since the study drug may impair the effectiveness of oral contraceptives), double barrier methods (diaphragm with spermicidal gel or condoms with contraceptive foam), Depo-Provera, partner vasectomy, total abstinence, and willing to continue the effective contraception method for 30 days after the last dose of AVX901;",
            "criterions": [
                {
                    "exact_snippets": "Female patients must be of non child-bearing potential",
                    "criterion": "female patients",
                    "requirements": [
                        {
                            "requirement_type": "child-bearing potential",
                            "expected_value": "non child-bearing potential"
                        }
                    ]
                },
                {
                    "exact_snippets": "use effective contraception",
                    "criterion": "contraception use",
                    "requirements": [
                        {
                            "requirement_type": "effectiveness",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "willing to continue the effective contraception method for 30 days after the last dose of AVX901",
                    "criterion": "contraception duration",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "30 days after the last dose of AVX901"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Ability to return to Duke University Medical Center for adequate follow-up as required by this protocol;",
            "criterions": [
                {
                    "exact_snippets": "Ability to return to Duke University Medical Center for adequate follow-up",
                    "criterion": "ability to return to Duke University Medical Center",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "adequate follow-up as required by this protocol",
                    "criterion": "adequate follow-up",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Current therapy with endocrine agents (tamoxifen, raloxifene, torimifene and all aromatase inhibitors) and/or bisphosphonates and/or RANK-ligand inhibitors is permitted.",
            "criterions": [
                {
                    "exact_snippets": "Current therapy with endocrine agents (tamoxifen, raloxifene, torimifene and all aromatase inhibitors)",
                    "criterion": "current therapy with endocrine agents",
                    "requirements": [
                        {
                            "requirement_type": "permitted",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Current therapy with ... bisphosphonates",
                    "criterion": "current therapy with bisphosphonates",
                    "requirements": [
                        {
                            "requirement_type": "permitted",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Current therapy with ... RANK-ligand inhibitors",
                    "criterion": "current therapy with RANK-ligand inhibitors",
                    "requirements": [
                        {
                            "requirement_type": "permitted",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Except for patients on the concurrent HER2 targeted therapy (cohort 2) cohort, patients may not receive cytotoxic chemotherapy, monoclonal antibodies (other than RANK-ligand inhibitors being used for bone protection), HER2 targeted therapy such as lapatinib, or radiation therapy in the 3 weeks before the first injection, during the injection period or for at least 2 weeks after the last injection. Patients may have received prior radiation including for brain metastases.",
            "criterions": [
                {
                    "exact_snippets": "patients may not receive cytotoxic chemotherapy ... in the 3 weeks before the first injection",
                    "criterion": "cytotoxic chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "not in the 3 weeks before the first injection"
                        }
                    ]
                },
                {
                    "exact_snippets": "patients may not receive cytotoxic chemotherapy ... during the injection period",
                    "criterion": "cytotoxic chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "not during the injection period"
                        }
                    ]
                },
                {
                    "exact_snippets": "patients may not receive cytotoxic chemotherapy ... for at least 2 weeks after the last injection",
                    "criterion": "cytotoxic chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "not for at least 2 weeks after the last injection"
                        }
                    ]
                },
                {
                    "exact_snippets": "patients may not receive ... monoclonal antibodies (other than RANK-ligand inhibitors being used for bone protection) ... in the 3 weeks before the first injection",
                    "criterion": "monoclonal antibodies",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "not in the 3 weeks before the first injection"
                        }
                    ]
                },
                {
                    "exact_snippets": "patients may not receive ... monoclonal antibodies (other than RANK-ligand inhibitors being used for bone protection) ... during the injection period",
                    "criterion": "monoclonal antibodies",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "not during the injection period"
                        }
                    ]
                },
                {
                    "exact_snippets": "patients may not receive ... monoclonal antibodies (other than RANK-ligand inhibitors being used for bone protection) ... for at least 2 weeks after the last injection",
                    "criterion": "monoclonal antibodies",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "not for at least 2 weeks after the last injection"
                        }
                    ]
                },
                {
                    "exact_snippets": "patients may not receive ... HER2 targeted therapy such as lapatinib ... in the 3 weeks before the first injection",
                    "criterion": "HER2 targeted therapy",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "not in the 3 weeks before the first injection"
                        }
                    ]
                },
                {
                    "exact_snippets": "patients may not receive ... HER2 targeted therapy such as lapatinib ... during the injection period",
                    "criterion": "HER2 targeted therapy",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "not during the injection period"
                        }
                    ]
                },
                {
                    "exact_snippets": "patients may not receive ... HER2 targeted therapy such as lapatinib ... for at least 2 weeks after the last injection",
                    "criterion": "HER2 targeted therapy",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "not for at least 2 weeks after the last injection"
                        }
                    ]
                },
                {
                    "exact_snippets": "patients may not receive ... radiation therapy in the 3 weeks before the first injection",
                    "criterion": "radiation therapy",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "not in the 3 weeks before the first injection"
                        }
                    ]
                },
                {
                    "exact_snippets": "patients may not receive ... radiation therapy ... during the injection period",
                    "criterion": "radiation therapy",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "not during the injection period"
                        }
                    ]
                },
                {
                    "exact_snippets": "patients may not receive ... radiation therapy ... for at least 2 weeks after the last injection",
                    "criterion": "radiation therapy",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "not for at least 2 weeks after the last injection"
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients may have received prior radiation including for brain metastases",
                    "criterion": "prior radiation",
                    "requirements": [
                        {
                            "requirement_type": "allowance",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of auto-immune disease such as, but not restricted to, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis. Prior history of autoimmune thyroiditis or vitiligo is permitted.",
            "criterions": [
                {
                    "exact_snippets": "History of auto-immune disease such as, but not restricted to, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis.",
                    "criterion": "auto-immune disease",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior history of autoimmune thyroiditis or vitiligo is permitted.",
                    "criterion": "autoimmune thyroiditis or vitiligo",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Serious chronic or acute illness considered by the P.I. to constitute an unwarranted high risk for investigational drug treatment.",
            "criterions": [
                {
                    "exact_snippets": "Serious chronic or acute illness",
                    "criterion": "illness",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "serious"
                        },
                        {
                            "requirement_type": "duration",
                            "expected_value": [
                                "chronic",
                                "acute"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "considered by the P.I. to constitute an unwarranted high risk",
                    "criterion": "risk assessment by P.I.",
                    "requirements": [
                        {
                            "requirement_type": "risk level",
                            "expected_value": "unwarranted high risk"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Medical or psychological impediment to probable compliance with the protocol.",
            "criterions": [
                {
                    "exact_snippets": "Medical ... impediment to probable compliance with the protocol.",
                    "criterion": "medical impediment",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "psychological impediment to probable compliance with the protocol.",
                    "criterion": "psychological impediment",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Concurrent or prior second malignancy (within the past 5 years) other than non-melanoma skin cancer, controlled superficial bladder cancer or controlled cervical cancer.",
            "criterions": [
                {
                    "exact_snippets": "Concurrent or prior second malignancy (within the past 5 years)",
                    "criterion": "second malignancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "non-melanoma skin cancer",
                    "criterion": "non-melanoma skin cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "controlled superficial bladder cancer",
                    "criterion": "superficial bladder cancer",
                    "requirements": [
                        {
                            "requirement_type": "control status",
                            "expected_value": "controlled"
                        }
                    ]
                },
                {
                    "exact_snippets": "controlled cervical cancer",
                    "criterion": "cervical cancer",
                    "requirements": [
                        {
                            "requirement_type": "control status",
                            "expected_value": "controlled"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Presence of active infection or systemic use of antimicrobials within 72 hours prior to the first injection",
            "criterions": [
                {
                    "exact_snippets": "Presence of active infection",
                    "criterion": "active infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "systemic use of antimicrobials within 72 hours prior to the first injection",
                    "criterion": "systemic use of antimicrobials",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 72,
                                "unit": "hours"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients on steroid therapy (or other immunosuppressives such as azathioprine or cyclosporine A) are excluded on the basis of potential immune suppression. Patients must have had 6 weeks of discontinuation of any steroid therapy prior to enrollment (except steroids used as anti-emetics for systemic chemotherapy which are permitted).",
            "criterions": [
                {
                    "exact_snippets": "Patients on steroid therapy (or other immunosuppressives such as azathioprine or cyclosporine A) are excluded",
                    "criterion": "steroid therapy or other immunosuppressives",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients must have had 6 weeks of discontinuation of any steroid therapy prior to enrollment",
                    "criterion": "discontinuation of steroid therapy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 6,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "except steroids used as anti-emetics for systemic chemotherapy which are permitted",
                    "criterion": "steroids used as anti-emetics for systemic chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "use",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Presence of an active acute or chronic infection including HIV (as determined by ELISA and confirmed by Western Blot) or viral hepatitis (as determined by HBsAg and Hepatitis C serology). Patients with HIV are excluded based on immuno-suppression, which may render them unable to respond to the vaccine; patients with chronic hepatitis are excluded because of concern that hepatitis could be exacerbated by the injections. .",
            "criterions": [
                {
                    "exact_snippets": "Presence of an active acute or chronic infection including HIV",
                    "criterion": "active acute or chronic infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "HIV (as determined by ELISA and confirmed by Western Blot)",
                    "criterion": "HIV infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "viral hepatitis (as determined by HBsAg and Hepatitis C serology)",
                    "criterion": "viral hepatitis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Pregnant or nursing women",
            "criterions": [
                {
                    "exact_snippets": "Pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "nursing women",
                    "criterion": "nursing",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": [
        {
            "line": "Inclusion criteria",
            "criterions": []
        },
        {
            "line": "* Patients have received a a trastuzumab, trastuzumab + pertuzumab, or T-DM1-based therapy for locally advanced or metastatic disease for a minimum of 9 weeks duration. Patients may have received more than 1 trastuzumab-based combination therapy.",
            "criterions": [
                {
                    "exact_snippets": "Patients have received a trastuzumab, trastuzumab + pertuzumab, or T-DM1-based therapy",
                    "criterion": "therapy type",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "trastuzumab",
                                "trastuzumab + pertuzumab",
                                "T-DM1-based"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "for locally advanced or metastatic disease",
                    "criterion": "disease stage",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "locally advanced",
                                "metastatic"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "for a minimum of 9 weeks duration",
                    "criterion": "therapy duration",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 9,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients may have received more than 1 trastuzumab-based combination therapy",
                    "criterion": "trastuzumab-based combination therapy count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": ">1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Written informed consent obtained from the patient prior to performing any study-related procedures, including screening visits. however, CT scans, bone scans, MUGA, Echocardiogram, EKG,and labs performed as standard of care prior to signing consent can be used to fulfill eligibility requirements if they were performed within 8 weeks of the first dose of AVX901 (for the MUGA or echocardiogram) and within 4 weeksof the first dose of study drug for the remainder of the studies",
            "criterions": [
                {
                    "exact_snippets": "Written informed consent obtained from the patient",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "CT scans, bone scans, MUGA, Echocardiogram, EKG, and labs performed as standard of care ... within 8 weeks of the first dose of AVX901 (for the MUGA or echocardiogram)",
                    "criterion": "MUGA or echocardiogram timing",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 8,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "CT scans, bone scans, MUGA, Echocardiogram, EKG, and labs performed as standard of care ... within 4 weeks of the first dose of study drug for the remainder of the studies",
                    "criterion": "other studies timing",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Exclusion criteria",
            "criterions": []
        }
    ]
}