{
    "info": {
        "nct_id": "NCT00931931",
        "official_title": "A Phase I Dose Escalation Study of Intratumoral or Intravenous Herpes Simplex Virus-1 Mutant HSV1716 in Patients With Refractory Non-Central Nervous System (Non-CNS) Solid Tumors",
        "inclusion_criteria": "Inclusion of Women and Minorities: The study is open to all participants regardless of gender or ethnicity.\n\nInclusion for intratumoral injection: Subject must have 1-3 lesions amenable to HSV1716 administration by needle if superficial; by needle and/or catheter if deep or pulmonary, via interventional radiology without undue risk. Lesion(s) must meet size criteria specified in section 4.4.9.\n\nInclusion for intravenous administration: Subject must have metastatic disease or a lesion not deemed suitable for direct injection.\n\n* Age: Subjects must be greater than or equal to 7 years and less than or equal to 30 years of age at the time of signing consent (study entry);\n* Histologic Diagnosis: Subjects must have had histologic verification a non-CNS solid tumor at original diagnosis. The tumor must be amenable to HSV1716 administration without undue risk. Disease must be considered refractory to conventional therapy or for which no conventional therapy exists.\n* Metastatic Disease: Subjects who have metastasis to the brain are eligible for the intratumoral arm of this study; however, no metastatic sites within the brain will be considered for injection. Subjects who have metastasis to the brain are eligible for the intravenous arm of this study only if those metastases have been treated and are no longer active.\n* Performance Level: Karnofsky greater than or equal to 50. Subjects who are unable to walk because of paralysis, but who are up in a wheelchair will be considered ambulatory for the purpose of assessing the performance score.\n* Subjects must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study;\n* Myelosuppressive chemotherapy: Must not have received within 28 days of entry onto this study (42 days if prior nitrosourea) accompanied by hematopoietic recovery, or 14 days of stopping non-myelosuppressive therapy as long as hematopoietic requirements are met;\n* Biologic (anti-neoplastic agent): Must not have received within 7 days of entry onto this study (21 days if prior VEGF-Trap and at least 3 half-lives after last dose of a monoclonal antibody). For biologic agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur;\n* No Radiation Therapy greater than or equal to 14 days for local palliative XRT (small port): greater than or equal to 6 months must have elapsed if prior craniospinal XRT or if greater than or equal to 50% radiation of pelvis; greater than or equal to 42 days must have elapsed if other substantial bone marrow radiation;\n* Immunoablative or myeloablative Stem Cell Transplant (SCT): greater than or equal to 6 months must have elapsed from prior autologous transplant. Subjects must not have graft versus host disease post autologous transplant;\n* Investigational agent: greater than or equal to 28 days must have elapsed from treatment with a different phase I agent;\n* Subjects with seizure disorder may be enrolled if on anticonvulsants and well controlled.\n* At the time of enrollment, specified CNS conditions must be less than or equal to Grade II toxicity per CTCAE 3.0 criteria;\n* All subjects must have adequate blood counts defined as: peripheral absolute neutrophil count (ANC) greater than or equal to 750/uL, Platelet count greater than or equal to 100,000/uL (may be a post transfusion value), Hemoglobin greater than or equal to 9.0 gm/dL (may be a post transfusion value)\n* Adequate renal function defined as:Serum creatinine less than or equal to 1.5 x upper limit of normal (ULN) for age or creatinine clearance or radioisotope GFR greater than or equal to 70 ml/min/1.73 m2;\n* Adequate liver function defined as: Total bilirubin less than or equal to 2.0 x ULN for age, and SGPT (ALT) less than or equal to 2.5 x ULN for age and albumin greater than or equal to 2g/dL, GGT < 2.5 x ULN\n* Adequate cardiac function as defined by: Shortening fraction >25% by echocardiogram or ejection fraction above the institutional lower limit of normal by MUGA, No focal wall motion abnormalities as determined by either of the above studies, EKG without evidence of ischemia or significant arrythmia\n* Adequate coagulation as defined by:PT/INR and PTT <1.5 x ULN for age;\n* Infectious Disease: Documented evidence of negative tests for the presence of Hepatitis B surface antigen, Hepatitis C antibody, HIV1 and HIV2 antibodies within the three months preceding study entry. Subjects who do not have such evidence must undergo appropriate testing prior to virus administration;\nHealthy volunteers allowed\nMust have minimum age of 7 Years\nMust have maximum age of 30 Years",
        "exclusion_criteria": "* Stem cell transplant: No subjects who have received an allogeneic hematopoietic stem cell transplant are eligible;\n* Pregnancy or Breast-Feeding: There is no available information regarding human fetal or teratogenic toxicities. Pregnant women are excluded and pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method from the time of study entry to a period of no less than four months post the final HSV1716 injection. For the same period of time, women who participate in this study must agree not to breast feed;\n* Consent: Unable or unwilling to give voluntary informed consent / assent;\n* Leukemia: Subjects with leukemia are not eligible for study participation;\n* Infection or any other severe systemic disease or medical or surgical condition deemed significant by the principal investigator;\n* Administration of any unlicensed or investigational agent within 4 weeks of entry to the study;\n* Growth factor(s): No PEG-GCSF within 14 days of virus injection (day 0);\n* Anti-HSV antivirals: Subjects whose physicians determine that anti-HSV antiviral therapy (such as acyclovir, ganciclovir, foscarnet, etc.) cannot be safely discontinued from 2 days prior to the injection to 28 days following the injection should not be in the study.\n* Subjects who have other conditions which in the opinion of the investigator contra-indicate the receipt of HSV1716 or indicate subject's inability to follow protocol requirements.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "Inclusion of Women and Minorities: The study is open to all participants regardless of gender or ethnicity.",
            "criterions": [
                {
                    "exact_snippets": "regardless of gender",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "inclusion",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "regardless of ... ethnicity",
                    "criterion": "ethnicity",
                    "requirements": [
                        {
                            "requirement_type": "inclusion",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Inclusion for intratumoral injection: Subject must have 1-3 lesions amenable to HSV1716 administration by needle if superficial; by needle and/or catheter if deep or pulmonary, via interventional radiology without undue risk. Lesion(s) must meet size criteria specified in section 4.4.9.",
            "criterions": [
                {
                    "exact_snippets": "1-3 lesions",
                    "criterion": "number of lesions",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 1,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 3,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "lesions amenable to HSV1716 administration by needle if superficial; by needle and/or catheter if deep or pulmonary",
                    "criterion": "lesion amenability to HSV1716 administration",
                    "requirements": [
                        {
                            "requirement_type": "method of administration",
                            "expected_value": [
                                "needle",
                                "needle and/or catheter"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "via interventional radiology without undue risk",
                    "criterion": "interventional radiology risk",
                    "requirements": [
                        {
                            "requirement_type": "risk",
                            "expected_value": "without undue risk"
                        }
                    ]
                },
                {
                    "exact_snippets": "Lesion(s) must meet size criteria specified in section 4.4.9.",
                    "criterion": "lesion size",
                    "requirements": [
                        {
                            "requirement_type": "size criteria",
                            "expected_value": "specified in section 4.4.9"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Inclusion for intravenous administration: Subject must have metastatic disease or a lesion not deemed suitable for direct injection.",
            "criterions": [
                {
                    "exact_snippets": "Subject must have metastatic disease",
                    "criterion": "metastatic disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "a lesion not deemed suitable for direct injection",
                    "criterion": "lesion suitability for direct injection",
                    "requirements": [
                        {
                            "requirement_type": "suitability",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Age: Subjects must be greater than or equal to 7 years and less than or equal to 30 years of age at the time of signing consent (study entry);",
            "criterions": [
                {
                    "exact_snippets": "Age: Subjects must be greater than or equal to 7 years and less than or equal to 30 years of age",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 7,
                                        "unit": "years"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 30,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Histologic Diagnosis: Subjects must have had histologic verification a non-CNS solid tumor at original diagnosis. The tumor must be amenable to HSV1716 administration without undue risk. Disease must be considered refractory to conventional therapy or for which no conventional therapy exists.",
            "criterions": [
                {
                    "exact_snippets": "histologic verification a non-CNS solid tumor",
                    "criterion": "histologic diagnosis",
                    "requirements": [
                        {
                            "requirement_type": "verification",
                            "expected_value": "non-CNS solid tumor"
                        }
                    ]
                },
                {
                    "exact_snippets": "tumor must be amenable to HSV1716 administration",
                    "criterion": "tumor amenability",
                    "requirements": [
                        {
                            "requirement_type": "amenability",
                            "expected_value": "HSV1716 administration"
                        }
                    ]
                },
                {
                    "exact_snippets": "Disease must be considered refractory to conventional therapy or for which no conventional therapy exists",
                    "criterion": "disease status",
                    "requirements": [
                        {
                            "requirement_type": "refractory status",
                            "expected_value": "refractory to conventional therapy"
                        },
                        {
                            "requirement_type": "availability of conventional therapy",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Metastatic Disease: Subjects who have metastasis to the brain are eligible for the intratumoral arm of this study; however, no metastatic sites within the brain will be considered for injection. Subjects who have metastasis to the brain are eligible for the intravenous arm of this study only if those metastases have been treated and are no longer active.",
            "criterions": [
                {
                    "exact_snippets": "metastasis to the brain ... eligible for the intratumoral arm",
                    "criterion": "brain metastasis",
                    "requirements": [
                        {
                            "requirement_type": "eligibility for intratumoral arm",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "metastasis to the brain ... eligible for the intravenous arm ... only if those metastases have been treated and are no longer active",
                    "criterion": "brain metastasis",
                    "requirements": [
                        {
                            "requirement_type": "eligibility for intravenous arm",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "treated"
                        },
                        {
                            "requirement_type": "activity status",
                            "expected_value": "no longer active"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Performance Level: Karnofsky greater than or equal to 50. Subjects who are unable to walk because of paralysis, but who are up in a wheelchair will be considered ambulatory for the purpose of assessing the performance score.",
            "criterions": [
                {
                    "exact_snippets": "Performance Level: Karnofsky greater than or equal to 50.",
                    "criterion": "Karnofsky Performance Status",
                    "requirements": [
                        {
                            "requirement_type": "score",
                            "expected_value": {
                                "operator": ">=",
                                "value": 50,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Subjects who are unable to walk because of paralysis, but who are up in a wheelchair will be considered ambulatory",
                    "criterion": "ambulatory status",
                    "requirements": [
                        {
                            "requirement_type": "condition",
                            "expected_value": "up in a wheelchair"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Subjects must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study;",
            "criterions": [
                {
                    "exact_snippets": "fully recovered from the acute toxic effects of all prior chemotherapy",
                    "criterion": "recovery from acute toxic effects of prior chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "recovery",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "fully recovered from the acute toxic effects of all prior ... immunotherapy",
                    "criterion": "recovery from acute toxic effects of prior immunotherapy",
                    "requirements": [
                        {
                            "requirement_type": "recovery",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "fully recovered from the acute toxic effects of all prior ... radiotherapy",
                    "criterion": "recovery from acute toxic effects of prior radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "recovery",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Myelosuppressive chemotherapy: Must not have received within 28 days of entry onto this study (42 days if prior nitrosourea) accompanied by hematopoietic recovery, or 14 days of stopping non-myelosuppressive therapy as long as hematopoietic requirements are met;",
            "criterions": [
                {
                    "exact_snippets": "Myelosuppressive chemotherapy: Must not have received within 28 days of entry onto this study",
                    "criterion": "myelosuppressive chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": ">=",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "42 days if prior nitrosourea",
                    "criterion": "nitrosourea",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": ">=",
                                "value": 42,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "accompanied by hematopoietic recovery",
                    "criterion": "hematopoietic recovery",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "14 days of stopping non-myelosuppressive therapy",
                    "criterion": "non-myelosuppressive therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "operator": ">=",
                                "value": 14,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "as long as hematopoietic requirements are met",
                    "criterion": "hematopoietic requirements",
                    "requirements": [
                        {
                            "requirement_type": "met",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Biologic (anti-neoplastic agent): Must not have received within 7 days of entry onto this study (21 days if prior VEGF-Trap and at least 3 half-lives after last dose of a monoclonal antibody). For biologic agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur;",
            "criterions": [
                {
                    "exact_snippets": "Biologic (anti-neoplastic agent): Must not have received within 7 days of entry onto this study",
                    "criterion": "biologic anti-neoplastic agent",
                    "requirements": [
                        {
                            "requirement_type": "time since last administration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 7,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "21 days if prior VEGF-Trap",
                    "criterion": "VEGF-Trap",
                    "requirements": [
                        {
                            "requirement_type": "time since last administration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 21,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "at least 3 half-lives after last dose of a monoclonal antibody",
                    "criterion": "monoclonal antibody",
                    "requirements": [
                        {
                            "requirement_type": "time since last administration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "half-lives"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "biologic agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur",
                    "criterion": "biologic agents with known adverse events",
                    "requirements": [
                        {
                            "requirement_type": "time since last administration",
                            "expected_value": "beyond the time during which adverse events are known to occur"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* No Radiation Therapy greater than or equal to 14 days for local palliative XRT (small port): greater than or equal to 6 months must have elapsed if prior craniospinal XRT or if greater than or equal to 50% radiation of pelvis; greater than or equal to 42 days must have elapsed if other substantial bone marrow radiation;",
            "criterions": [
                {
                    "exact_snippets": "No Radiation Therapy greater than or equal to 14 days for local palliative XRT (small port)",
                    "criterion": "local palliative XRT (small port)",
                    "requirements": [
                        {
                            "requirement_type": "elapsed time since therapy",
                            "expected_value": {
                                "operator": ">=",
                                "value": 14,
                                "unit": "days"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "greater than or equal to 6 months must have elapsed if prior craniospinal XRT",
                    "criterion": "prior craniospinal XRT",
                    "requirements": [
                        {
                            "requirement_type": "elapsed time since therapy",
                            "expected_value": {
                                "operator": ">=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "greater than or equal to 6 months must have elapsed ... if greater than or equal to 50% radiation of pelvis",
                    "criterion": "radiation of pelvis",
                    "requirements": [
                        {
                            "requirement_type": "percentage of pelvis radiated",
                            "expected_value": {
                                "operator": ">=",
                                "value": 50,
                                "unit": "%"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "greater than or equal to 42 days must have elapsed if other substantial bone marrow radiation",
                    "criterion": "other substantial bone marrow radiation",
                    "requirements": [
                        {
                            "requirement_type": "elapsed time since therapy",
                            "expected_value": {
                                "operator": ">=",
                                "value": 42,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Immunoablative or myeloablative Stem Cell Transplant (SCT): greater than or equal to 6 months must have elapsed from prior autologous transplant. Subjects must not have graft versus host disease post autologous transplant;",
            "criterions": [
                {
                    "exact_snippets": "Immunoablative or myeloablative Stem Cell Transplant (SCT)",
                    "criterion": "type of Stem Cell Transplant",
                    "requirements": [
                        {
                            "requirement_type": "expected types",
                            "expected_value": [
                                "immunoablative",
                                "myeloablative"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "greater than or equal to 6 months must have elapsed from prior autologous transplant",
                    "criterion": "time since prior autologous transplant",
                    "requirements": [
                        {
                            "requirement_type": "elapsed time",
                            "expected_value": {
                                "operator": ">=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Subjects must not have graft versus host disease post autologous transplant",
                    "criterion": "graft versus host disease post autologous transplant",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Investigational agent: greater than or equal to 28 days must have elapsed from treatment with a different phase I agent;",
            "criterions": [
                {
                    "exact_snippets": "greater than or equal to 28 days must have elapsed from treatment with a different phase I agent",
                    "criterion": "elapsed time since treatment with a different phase I agent",
                    "requirements": [
                        {
                            "requirement_type": "time elapsed",
                            "expected_value": {
                                "operator": ">=",
                                "value": 28,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Subjects with seizure disorder may be enrolled if on anticonvulsants and well controlled.",
            "criterions": [
                {
                    "exact_snippets": "Subjects with seizure disorder",
                    "criterion": "seizure disorder",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "if on anticonvulsants",
                    "criterion": "anticonvulsant use",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "well controlled",
                    "criterion": "seizure control",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "well controlled"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* At the time of enrollment, specified CNS conditions must be less than or equal to Grade II toxicity per CTCAE 3.0 criteria;",
            "criterions": [
                {
                    "exact_snippets": "specified CNS conditions ... less than or equal to Grade II toxicity per CTCAE 3.0 criteria",
                    "criterion": "CNS conditions",
                    "requirements": [
                        {
                            "requirement_type": "toxicity grade",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "Grade (CTCAE 3.0)"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* All subjects must have adequate blood counts defined as: peripheral absolute neutrophil count (ANC) greater than or equal to 750/uL, Platelet count greater than or equal to 100,000/uL (may be a post transfusion value), Hemoglobin greater than or equal to 9.0 gm/dL (may be a post transfusion value)",
            "criterions": [
                {
                    "exact_snippets": "peripheral absolute neutrophil count (ANC) greater than or equal to 750/uL",
                    "criterion": "peripheral absolute neutrophil count (ANC)",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 750,
                                "unit": "uL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Platelet count greater than or equal to 100,000/uL (may be a post transfusion value)",
                    "criterion": "Platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100000,
                                "unit": "uL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Hemoglobin greater than or equal to 9.0 gm/dL (may be a post transfusion value)",
                    "criterion": "Hemoglobin",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 9.0,
                                "unit": "gm/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate renal function defined as:Serum creatinine less than or equal to 1.5 x upper limit of normal (ULN) for age or creatinine clearance or radioisotope GFR greater than or equal to 70 ml/min/1.73 m2;",
            "criterions": [
                {
                    "exact_snippets": "Serum creatinine less than or equal to 1.5 x upper limit of normal (ULN) for age",
                    "criterion": "serum creatinine",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1.5,
                                "unit": "x ULN for age"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "creatinine clearance or radioisotope GFR greater than or equal to 70 ml/min/1.73 m2",
                    "criterion": "creatinine clearance or radioisotope GFR",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 70,
                                "unit": "ml/min/1.73 m2"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate liver function defined as: Total bilirubin less than or equal to 2.0 x ULN for age, and SGPT (ALT) less than or equal to 2.5 x ULN for age and albumin greater than or equal to 2g/dL, GGT < 2.5 x ULN",
            "criterions": [
                {
                    "exact_snippets": "Total bilirubin less than or equal to 2.0 x ULN for age",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.0,
                                "unit": "x ULN for age"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "SGPT (ALT) less than or equal to 2.5 x ULN for age",
                    "criterion": "SGPT (ALT)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "x ULN for age"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "albumin greater than or equal to 2g/dL",
                    "criterion": "albumin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "g/dL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "GGT < 2.5 x ULN",
                    "criterion": "GGT",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<",
                                "value": 2.5,
                                "unit": "x ULN"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate cardiac function as defined by: Shortening fraction >25% by echocardiogram or ejection fraction above the institutional lower limit of normal by MUGA, No focal wall motion abnormalities as determined by either of the above studies, EKG without evidence of ischemia or significant arrythmia",
            "criterions": [
                {
                    "exact_snippets": "Adequate cardiac function as defined by: Shortening fraction >25% by echocardiogram",
                    "criterion": "cardiac function",
                    "requirements": [
                        {
                            "requirement_type": "shortening fraction",
                            "expected_value": {
                                "operator": ">",
                                "value": 25,
                                "unit": "%"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate cardiac function as defined by: ... ejection fraction above the institutional lower limit of normal by MUGA",
                    "criterion": "cardiac function",
                    "requirements": [
                        {
                            "requirement_type": "ejection fraction",
                            "expected_value": "above the institutional lower limit of normal"
                        }
                    ]
                },
                {
                    "exact_snippets": "No focal wall motion abnormalities as determined by either of the above studies",
                    "criterion": "focal wall motion abnormalities",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "EKG without evidence of ischemia",
                    "criterion": "ischemia",
                    "requirements": [
                        {
                            "requirement_type": "evidence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "EKG without evidence of ... significant arrythmia",
                    "criterion": "arrythmia",
                    "requirements": [
                        {
                            "requirement_type": "significance",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate coagulation as defined by:PT/INR and PTT <1.5 x ULN for age;",
            "criterions": [
                {
                    "exact_snippets": "Adequate coagulation as defined by:PT/INR and PTT <1.5 x ULN for age",
                    "criterion": "coagulation",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "PT/INR ... <1.5 x ULN for age",
                    "criterion": "PT/INR",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<",
                                "value": 1.5,
                                "unit": "x ULN for age"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "PTT <1.5 x ULN for age",
                    "criterion": "PTT",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<",
                                "value": 1.5,
                                "unit": "x ULN for age"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Infectious Disease: Documented evidence of negative tests for the presence of Hepatitis B surface antigen, Hepatitis C antibody, HIV1 and HIV2 antibodies within the three months preceding study entry. Subjects who do not have such evidence must undergo appropriate testing prior to virus administration;",
            "criterions": [
                {
                    "exact_snippets": "Documented evidence of negative tests for the presence of Hepatitis B surface antigen",
                    "criterion": "Hepatitis B surface antigen",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Documented evidence of negative tests for the presence of ... Hepatitis C antibody",
                    "criterion": "Hepatitis C antibody",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Documented evidence of negative tests for the presence of ... HIV1 and HIV2 antibodies",
                    "criterion": "HIV1 and HIV2 antibodies",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have minimum age of 7 Years",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 7 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 7,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have maximum age of 30 Years",
            "criterions": [
                {
                    "exact_snippets": "maximum age of 30 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "maximum",
                            "expected_value": {
                                "operator": "<=",
                                "value": 30,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "* Stem cell transplant: No subjects who have received an allogeneic hematopoietic stem cell transplant are eligible;",
            "criterions": [
                {
                    "exact_snippets": "received an allogeneic hematopoietic stem cell transplant",
                    "criterion": "allogeneic hematopoietic stem cell transplant",
                    "requirements": [
                        {
                            "requirement_type": "received",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Pregnancy or Breast-Feeding: There is no available information regarding human fetal or teratogenic toxicities. Pregnant women are excluded and pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method from the time of study entry to a period of no less than four months post the final HSV1716 injection. For the same period of time, women who participate in this study must agree not to breast feed;",
            "criterions": [
                {
                    "exact_snippets": "Pregnancy or Breast-Feeding: ... Pregnant women are excluded",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "pregnancy tests must be obtained in girls who are post-menarchal",
                    "criterion": "pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method",
                    "criterion": "use of contraceptive method",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "women who participate in this study must agree not to breast feed",
                    "criterion": "breast-feeding",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Consent: Unable or unwilling to give voluntary informed consent / assent;",
            "criterions": [
                {
                    "exact_snippets": "Unable or unwilling to give voluntary informed consent / assent",
                    "criterion": "voluntary informed consent / assent",
                    "requirements": [
                        {
                            "requirement_type": "ability and willingness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Leukemia: Subjects with leukemia are not eligible for study participation;",
            "criterions": [
                {
                    "exact_snippets": "Leukemia: Subjects with leukemia are not eligible",
                    "criterion": "leukemia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Infection or any other severe systemic disease or medical or surgical condition deemed significant by the principal investigator;",
            "criterions": [
                {
                    "exact_snippets": "Infection",
                    "criterion": "infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "any other severe systemic disease",
                    "criterion": "severe systemic disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "medical or surgical condition deemed significant by the principal investigator",
                    "criterion": "medical or surgical condition",
                    "requirements": [
                        {
                            "requirement_type": "significance",
                            "expected_value": "deemed significant by the principal investigator"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Administration of any unlicensed or investigational agent within 4 weeks of entry to the study;",
            "criterions": [
                {
                    "exact_snippets": "Administration of any unlicensed or investigational agent within 4 weeks of entry to the study",
                    "criterion": "administration of unlicensed or investigational agent",
                    "requirements": [
                        {
                            "requirement_type": "time since last administration",
                            "expected_value": {
                                "operator": "<",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Growth factor(s): No PEG-GCSF within 14 days of virus injection (day 0);",
            "criterions": [
                {
                    "exact_snippets": "No PEG-GCSF within 14 days of virus injection (day 0)",
                    "criterion": "PEG-GCSF administration",
                    "requirements": [
                        {
                            "requirement_type": "time since last administration",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 14,
                                        "unit": "days"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Anti-HSV antivirals: Subjects whose physicians determine that anti-HSV antiviral therapy (such as acyclovir, ganciclovir, foscarnet, etc.) cannot be safely discontinued from 2 days prior to the injection to 28 days following the injection should not be in the study.",
            "criterions": [
                {
                    "exact_snippets": "Anti-HSV antivirals: Subjects whose physicians determine that anti-HSV antiviral therapy (such as acyclovir, ganciclovir, foscarnet, etc.) cannot be safely discontinued",
                    "criterion": "anti-HSV antiviral therapy",
                    "requirements": [
                        {
                            "requirement_type": "discontinuation",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Subjects who have other conditions which in the opinion of the investigator contra-indicate the receipt of HSV1716 or indicate subject's inability to follow protocol requirements.",
            "criterions": [
                {
                    "exact_snippets": "other conditions which in the opinion of the investigator contra-indicate the receipt of HSV1716",
                    "criterion": "contra-indicating conditions",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "inability to follow protocol requirements",
                    "criterion": "ability to follow protocol requirements",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}