{
    "info": {
        "nct_id": "NCT00291473",
        "official_title": "Safety and Immunogenicity of Cholesterol-Bearing Hydrophobized Pullulan HER2 Protein 146 (CHP-HER2) and NY-ESO-1 Protein (CHP-NY-ESO-1) in Combination With OK-432 in HER2- and/or NY-ESO-1-Expressing Cancers",
        "inclusion_criteria": "1. Histological confirmation of cancer.\n2. HER2 expression in tumor cells scored as 1+ or more which should be confirmed by IHC using at least two antibodies (archived issue; see Appendix 1 and Reference 1 for methodology).\n\n   or NY-ESO-1 expression by reverse transcriptase and polymerase chain reaction (RT-PCR) analysis (Appendix 2), preferably, or immunohistochemistry\n3. Patients must\n\n   1. are at high risk of recurrence, more than 25% of probability, after complete resection or even after post-operative adjuvant treatment, and effective adjuvant therapy is not available or refused; or\n   2. have metastatic disease, and treatment has failed, or in the situation where effective therapy is not available, or has been refused.\n4. Complete recovery from surgery (at least 4 weeks).\n5. Laboratory values within the following limits:\n\n   Hemoglobin 9.0 g/dL or more, or 10.0 g/dL or more if <50 kg Neutrophil count >1.5 x 109/L Lymphocyte count >0.5 x 109/L Platelet count >100 x 109/L Serum creatinine ≤ 1.8 mg/dL Serum bilirubin ≤ 2 mg/dL\n6. Performance status > 70 (Karnofsky Scale) and life expectancy >3 months.\n7. Age 18 years or more.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "1. Clinically significant heart disease (NYHA Class III or IV).\n2. Cardiac dysfunction; less than 50% of ejection fraction by echocardiogram.\n3. Immunodeficiency disease.\n4. Other serious illnesses, eg, serious infections requiring antibiotics, bleeding disorders.\n5. Previous bone marrow or stem cell transplant.\n6. Metastatic disease to the central nervous system, unless treated and stable.\n7. known HIV antibody positivity.\n8. Anaphylactic reaction to previous vaccination.\n9. Hypersensitivity to penicillin\n10. Chemotherapy, any type of radiation therapy, or immunotherapy within 4 weeks before study entry (6 weeks for nitrosoureas).\n11. Concomitant treatment with steroids. Topical or inhalational steroids are permitted.\n12. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.\n13. Pregnancy or nursing .\n14. Refusal, by women of childbearing potential, to use medically acceptable means of contraception.\n15. Mental impairment that may compromise the ability to give informed consent.\n16. Lack of availability for immunological and clinical follow-up assessment.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Histological confirmation of cancer.",
            "criterions": [
                {
                    "exact_snippets": "Histological confirmation of cancer",
                    "criterion": "cancer",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": "histological"
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. HER2 expression in tumor cells scored as 1+ or more which should be confirmed by IHC using at least two antibodies (archived issue; see Appendix 1 and Reference 1 for methodology).",
            "criterions": [
                {
                    "exact_snippets": "HER2 expression in tumor cells scored as 1+ or more",
                    "criterion": "HER2 expression",
                    "requirements": [
                        {
                            "requirement_type": "score",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "+"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "confirmed by IHC using at least two antibodies",
                    "criterion": "IHC confirmation",
                    "requirements": [
                        {
                            "requirement_type": "antibodies",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "antibodies"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "or NY-ESO-1 expression by reverse transcriptase and polymerase chain reaction (RT-PCR) analysis (Appendix 2), preferably, or immunohistochemistry",
            "criterions": [
                {
                    "exact_snippets": "NY-ESO-1 expression by reverse transcriptase and polymerase chain reaction (RT-PCR) analysis ... or immunohistochemistry",
                    "criterion": "NY-ESO-1 expression",
                    "requirements": [
                        {
                            "requirement_type": "detection method",
                            "expected_value": [
                                "RT-PCR",
                                "immunohistochemistry"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Patients must",
            "criterions": [
                {
                    "exact_snippets": "Patients must",
                    "criterion": "patient",
                    "requirements": [
                        {
                            "requirement_type": "N/A",
                            "expected_value": "must"
                        }
                    ]
                }
            ]
        },
        {
            "line": "1. are at high risk of recurrence, more than 25% of probability, after complete resection or even after post-operative adjuvant treatment, and effective adjuvant therapy is not available or refused; or",
            "criterions": [
                {
                    "exact_snippets": "are at high risk of recurrence, more than 25% of probability",
                    "criterion": "risk of recurrence",
                    "requirements": [
                        {
                            "requirement_type": "probability",
                            "expected_value": {
                                "operator": ">",
                                "value": 25,
                                "unit": "%"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "effective adjuvant therapy is not available",
                    "criterion": "availability of effective adjuvant therapy",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "effective adjuvant therapy ... refused",
                    "criterion": "refusal of effective adjuvant therapy",
                    "requirements": [
                        {
                            "requirement_type": "refusal",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. have metastatic disease, and treatment has failed, or in the situation where effective therapy is not available, or has been refused.",
            "criterions": [
                {
                    "exact_snippets": "have metastatic disease",
                    "criterion": "metastatic disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "treatment has failed",
                    "criterion": "treatment efficacy",
                    "requirements": [
                        {
                            "requirement_type": "efficacy",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "effective therapy is not available",
                    "criterion": "availability of effective therapy",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "effective therapy ... has been refused",
                    "criterion": "refusal of effective therapy",
                    "requirements": [
                        {
                            "requirement_type": "refusal",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Complete recovery from surgery (at least 4 weeks).",
            "criterions": [
                {
                    "exact_snippets": "Complete recovery from surgery (at least 4 weeks)",
                    "criterion": "recovery from surgery",
                    "requirements": [
                        {
                            "requirement_type": "completeness",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time since surgery",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Laboratory values within the following limits:",
            "criterions": [
                {
                    "exact_snippets": "Laboratory values",
                    "criterion": "laboratory values",
                    "requirements": [
                        {
                            "requirement_type": "limits",
                            "expected_value": "within the following limits"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Hemoglobin 9.0 g/dL or more, or 10.0 g/dL or more if <50 kg Neutrophil count >1.5 x 109/L Lymphocyte count >0.5 x 109/L Platelet count >100 x 109/L Serum creatinine ≤ 1.8 mg/dL Serum bilirubin ≤ 2 mg/dL",
            "criterions": [
                {
                    "exact_snippets": "Hemoglobin 9.0 g/dL or more, or 10.0 g/dL or more if <50 kg",
                    "criterion": "hemoglobin level",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 9.0,
                                        "unit": "g/dL"
                                    }
                                ]
                            }
                        },
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 10.0,
                                        "unit": "g/dL"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Neutrophil count >1.5 x 109/L",
                    "criterion": "neutrophil count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">",
                                        "value": 1.5,
                                        "unit": "x 109/L"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Lymphocyte count >0.5 x 109/L",
                    "criterion": "lymphocyte count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">",
                                        "value": 0.5,
                                        "unit": "x 109/L"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Platelet count >100 x 109/L",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">",
                                        "value": 100,
                                        "unit": "x 109/L"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Serum creatinine ≤ 1.8 mg/dL",
                    "criterion": "serum creatinine level",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 1.8,
                                        "unit": "mg/dL"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Serum bilirubin ≤ 2 mg/dL",
                    "criterion": "serum bilirubin level",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "mg/dL"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Performance status > 70 (Karnofsky Scale) and life expectancy >3 months.",
            "criterions": [
                {
                    "exact_snippets": "Performance status > 70 (Karnofsky Scale)",
                    "criterion": "performance status",
                    "requirements": [
                        {
                            "requirement_type": "scale",
                            "expected_value": "Karnofsky Scale"
                        },
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">",
                                "value": 70,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "life expectancy >3 months",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Age 18 years or more.",
            "criterions": [
                {
                    "exact_snippets": "Age 18 years or more",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "healthy volunteers",
                    "requirements": [
                        {
                            "requirement_type": "participation",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have minimum age of 18 Years",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 18 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "1. Clinically significant heart disease (NYHA Class III or IV).",
            "criterions": [
                {
                    "exact_snippets": "Clinically significant heart disease (NYHA Class III or IV)",
                    "criterion": "heart disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "NYHA Class III",
                                "NYHA Class IV"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Cardiac dysfunction; less than 50% of ejection fraction by echocardiogram.",
            "criterions": [
                {
                    "exact_snippets": "Cardiac dysfunction",
                    "criterion": "cardiac dysfunction",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "less than 50% of ejection fraction by echocardiogram",
                    "criterion": "ejection fraction",
                    "requirements": [
                        {
                            "requirement_type": "measurement",
                            "expected_value": {
                                "operator": "<",
                                "value": 50,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Immunodeficiency disease.",
            "criterions": [
                {
                    "exact_snippets": "Immunodeficiency disease.",
                    "criterion": "immunodeficiency disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Other serious illnesses, eg, serious infections requiring antibiotics, bleeding disorders.",
            "criterions": [
                {
                    "exact_snippets": "serious infections requiring antibiotics",
                    "criterion": "serious infections",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": "antibiotics"
                        }
                    ]
                },
                {
                    "exact_snippets": "bleeding disorders",
                    "criterion": "bleeding disorders",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Previous bone marrow or stem cell transplant.",
            "criterions": [
                {
                    "exact_snippets": "Previous bone marrow or stem cell transplant.",
                    "criterion": "bone marrow transplant",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Previous bone marrow or stem cell transplant.",
                    "criterion": "stem cell transplant",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Metastatic disease to the central nervous system, unless treated and stable.",
            "criterions": [
                {
                    "exact_snippets": "Metastatic disease to the central nervous system",
                    "criterion": "metastatic disease to the central nervous system",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "unless treated and stable",
                    "criterion": "treatment and stability of central nervous system metastases",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "stability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. known HIV antibody positivity.",
            "criterions": [
                {
                    "exact_snippets": "known HIV antibody positivity",
                    "criterion": "HIV antibody",
                    "requirements": [
                        {
                            "requirement_type": "positivity",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Anaphylactic reaction to previous vaccination.",
            "criterions": [
                {
                    "exact_snippets": "Anaphylactic reaction to previous vaccination",
                    "criterion": "anaphylactic reaction",
                    "requirements": [
                        {
                            "requirement_type": "cause",
                            "expected_value": "previous vaccination"
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Hypersensitivity to penicillin",
            "criterions": [
                {
                    "exact_snippets": "Hypersensitivity to penicillin",
                    "criterion": "hypersensitivity to penicillin",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Chemotherapy, any type of radiation therapy, or immunotherapy within 4 weeks before study entry (6 weeks for nitrosoureas).",
            "criterions": [
                {
                    "exact_snippets": "Chemotherapy ... within 4 weeks before study entry (6 weeks for nitrosoureas).",
                    "criterion": "chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "any type of radiation therapy ... within 4 weeks before study entry",
                    "criterion": "radiation therapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "immunotherapy within 4 weeks before study entry",
                    "criterion": "immunotherapy",
                    "requirements": [
                        {
                            "requirement_type": "time since last treatment",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 4,
                                        "unit": "weeks"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Concomitant treatment with steroids. Topical or inhalational steroids are permitted.",
            "criterions": [
                {
                    "exact_snippets": "Concomitant treatment with steroids.",
                    "criterion": "concomitant steroid treatment",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Topical or inhalational steroids are permitted.",
                    "criterion": "topical or inhalational steroid treatment",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.",
            "criterions": [
                {
                    "exact_snippets": "Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.",
                    "criterion": "participation in another clinical trial",
                    "requirements": [
                        {
                            "requirement_type": "time since last participation",
                            "expected_value": {
                                "operator": ">=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. Pregnancy or nursing .",
            "criterions": [
                {
                    "exact_snippets": "Pregnancy",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "nursing",
                    "criterion": "nursing",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "14. Refusal, by women of childbearing potential, to use medically acceptable means of contraception.",
            "criterions": [
                {
                    "exact_snippets": "women of childbearing potential",
                    "criterion": "women of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Refusal ... to use medically acceptable means of contraception",
                    "criterion": "use of medically acceptable means of contraception",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "15. Mental impairment that may compromise the ability to give informed consent.",
            "criterions": [
                {
                    "exact_snippets": "Mental impairment that may compromise the ability to give informed consent.",
                    "criterion": "mental impairment",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "may compromise the ability to give informed consent"
                        }
                    ]
                }
            ]
        },
        {
            "line": "16. Lack of availability for immunological and clinical follow-up assessment.",
            "criterions": [
                {
                    "exact_snippets": "Lack of availability for immunological ... follow-up assessment.",
                    "criterion": "immunological follow-up assessment",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Lack of availability for ... clinical follow-up assessment.",
                    "criterion": "clinical follow-up assessment",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}