{
    "info": {
        "nct_id": "NCT05721872",
        "official_title": "An Exploratory Phase I/II Single-center Clinical Trial of the Efficacy, Tolerability and Safety of Intravenous D-isoascorbic Acid With Arsenic Trioxide in Patients With Advanced/Metastatic Colorectal Cancer Who Have Exhausted Standard Therapy",
        "inclusion_criteria": "Healthy volunteers allowed\nMust have minimum age of 18 Years\nMust have maximum age of 75 Years",
        "exclusion_criteria": "",
        "miscellaneous_criteria": "Phase 1:\n\nINCLUSION CRITERIA:\n\n* informed consent to participate in the study\n* patients of the second clinical group with malignant neoplasms of a common/metastatic form that have exhausted standard therapy.\n* patients who have received at least 3 lines of standard therapy, including those with the use of targeted drugs, patients who have exhausted the possibilities of using specialized drugs, as part of the recommendations of treatment protocols\n* the presence of \"+\" KRAS / NRAS status of the primary tumor or metastatic focus (determined in LEKzone 2, codons 12, 13, 61)\n* ≥1 measurable lesion defined by RECIST v1.1\n* ECOG PS 0.1 or 2\n\nEXCLUSION CRITERIA:\n\n* age up to 18 years\n* pregnancy and lactation\n* patients with an autoimmune disease or with a medical diagnosis requiring systemic immunosuppression\n* decompensated diabetes mellitus\n* renal failure, urolithiasis\n* diabetes\n* thrombophlebitis, tendency to thrombosis\n* severe lung disease, dyspnea at rest, pleural effusion\n* cardiovascular insufficiency, ejection fraction of the heart <40%\n* sensory neuropathy of the 1st degree of any etiology\n* uncontrolled infections\n* persons from the category of \"vulnerable patients\" (homeless, military personnel, incapacitated, patients in emergency conditions, other persons who may be subjected to pressure);\n* Allergy in history and during screening (drug, pollen, etc.);\n* participation in any other clinical trial;\n* hypersensitivity to arsenic;\n* individual intolerance to ascorbic acid;\n* thrombophlebitis and thrombosis, a tendency to thrombosis in history;\n* increased blood clotting and pathologies associated with this deviation;\n* diabetes;\n* nephrolithiasis or nephrolithiasis;\n* the patient does not agree to perform the procedures required by the protocol and is unable to adhere to the schedule of procedures.\n* if the patients have any other laboratory or other abnormalities, in the opinion of the Investigator, that can harm the patients and the results of the study.\n\nPhase II:\n\nINCLUSION CRITERIA:\n\nfor both groups (30 patients, considering 20% decrease from the study):\n\n* informed consent to participate in the study\n* patients of the second clinical group with advanced/metastatic colorectal cancer\n* Patients must have previously received at least 3 lines of standard drug therapy, including those with the use of targeted drugs, who have exhausted the possibilities of using specialized drugs, as part of the recommendations of colorectal cancer treatment protocols - the presence of \"+\" KRAS / NRAS status of the primary tumor, or metastatic focus (determined in exon 2, codons 12, 13, 61)\n* ≥1 measurable lesion defined by RECIST v1.1\n* ECOG PS 0.1 or 2\n\nEXCLUSION CRITERIA:\n\n* age up to 18 years\n* patients with an autoimmune disease or with a medical diagnosis requiring systemic immunosuppression\n* decompensated diabetes mellitus\n* renal failure, urolithiasis\n* thrombophlebitis, tendency to thrombosis\n* severe lung disease, dyspnea at rest, pleural effusion\n* cardiovascular insufficiency, ejection fraction of the heart <40%\n* sensory neuropathy of the 1st degree of any etiology\n* uncontrolled infections\n* persons from the category of \"vulnerable patients\" (homeless, military personnel, incapacitated, patients in emergency conditions, other persons who may be subjected to pressure);\n* Allergy in history and during screening (drug, pollen, etc.);\n* participation in any other clinical trial;\n* hypersensitivity to arsenic;\n* individual intolerance to ascorbic acid;\n* thrombophlebitis and thrombosis, a tendency to thrombosis in history;\n* increased blood clotting and pathologies associated with this deviation;\n* diabetes;\n* nephrolithiasis or nephrolithiasis;\n* the patient does not agree to perform the procedures required by the protocol and is unable to adhere to the schedule of procedures.\n* if the patients have any other laboratory or other abnormalities, in the opinion of the Investigator, that can harm the patients and the results of the study."
    },
    "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"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have maximum age of 75 Years",
            "criterions": [
                {
                    "exact_snippets": "maximum age of 75 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "maximum",
                            "expected_value": {
                                "operator": "<=",
                                "value": 75,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [],
    "miscellaneous_lines": [
        {
            "line": "Phase 1:",
            "criterions": [
                {
                    "exact_snippets": "Phase 1",
                    "criterion": "trial phase",
                    "requirements": [
                        {
                            "requirement_type": "phase",
                            "expected_value": "1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* informed consent to participate in the study",
            "criterions": [
                {
                    "exact_snippets": "informed consent to participate in the study",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* patients of the second clinical group with malignant neoplasms of a common/metastatic form that have exhausted standard therapy.",
            "criterions": [
                {
                    "exact_snippets": "patients of the second clinical group",
                    "criterion": "clinical group",
                    "requirements": [
                        {
                            "requirement_type": "group",
                            "expected_value": "second"
                        }
                    ]
                },
                {
                    "exact_snippets": "malignant neoplasms",
                    "criterion": "neoplasms",
                    "requirements": [
                        {
                            "requirement_type": "malignancy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "common/metastatic form",
                    "criterion": "neoplasms",
                    "requirements": [
                        {
                            "requirement_type": "form",
                            "expected_value": [
                                "common",
                                "metastatic"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "exhausted standard therapy",
                    "criterion": "standard therapy",
                    "requirements": [
                        {
                            "requirement_type": "exhaustion",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* patients who have received at least 3 lines of standard therapy, including those with the use of targeted drugs, patients who have exhausted the possibilities of using specialized drugs, as part of the recommendations of treatment protocols",
            "criterions": [
                {
                    "exact_snippets": "patients who have received at least 3 lines of standard therapy",
                    "criterion": "lines of standard therapy",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "lines"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "including those with the use of targeted drugs",
                    "criterion": "use of targeted drugs",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "patients who have exhausted the possibilities of using specialized drugs",
                    "criterion": "possibilities of using specialized drugs",
                    "requirements": [
                        {
                            "requirement_type": "exhaustion",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "as part of the recommendations of treatment protocols",
                    "criterion": "adherence to treatment protocols",
                    "requirements": [
                        {
                            "requirement_type": "adherence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* the presence of \"+\" KRAS / NRAS status of the primary tumor or metastatic focus (determined in LEKzone 2, codons 12, 13, 61)",
            "criterions": [
                {
                    "exact_snippets": "presence of \"+\" KRAS / NRAS status",
                    "criterion": "KRAS / NRAS status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": "+"
                        }
                    ]
                },
                {
                    "exact_snippets": "primary tumor or metastatic focus",
                    "criterion": "tumor location",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "primary tumor",
                                "metastatic focus"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "determined in LEKzone 2, codons 12, 13, 61",
                    "criterion": "LEKzone 2 codons",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "codon 12",
                                "codon 13",
                                "codon 61"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* ≥1 measurable lesion defined by RECIST v1.1",
            "criterions": [
                {
                    "exact_snippets": "≥1 measurable lesion defined by RECIST v1.1",
                    "criterion": "measurable lesion",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "N/A"
                            }
                        },
                        {
                            "requirement_type": "definition",
                            "expected_value": "RECIST v1.1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* ECOG PS 0.1 or 2",
            "criterions": [
                {
                    "exact_snippets": "ECOG PS 0.1 or 2",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": [
                                "0",
                                "1",
                                "2"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* age up to 18 years",
            "criterions": [
                {
                    "exact_snippets": "age up to 18 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "maximum",
                            "expected_value": {
                                "operator": "<=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* pregnancy and lactation",
            "criterions": [
                {
                    "exact_snippets": "pregnancy",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "lactation",
                    "criterion": "lactation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* patients with an autoimmune disease or with a medical diagnosis requiring systemic immunosuppression",
            "criterions": [
                {
                    "exact_snippets": "patients with an autoimmune disease",
                    "criterion": "autoimmune disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "patients ... with a medical diagnosis requiring systemic immunosuppression",
                    "criterion": "medical diagnosis requiring systemic immunosuppression",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* decompensated diabetes mellitus",
            "criterions": [
                {
                    "exact_snippets": "decompensated diabetes mellitus",
                    "criterion": "diabetes mellitus",
                    "requirements": [
                        {
                            "requirement_type": "compensation status",
                            "expected_value": "decompensated"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* renal failure, urolithiasis",
            "criterions": [
                {
                    "exact_snippets": "renal failure",
                    "criterion": "renal failure",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "urolithiasis",
                    "criterion": "urolithiasis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* diabetes",
            "criterions": [
                {
                    "exact_snippets": "diabetes",
                    "criterion": "diabetes",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* thrombophlebitis, tendency to thrombosis",
            "criterions": [
                {
                    "exact_snippets": "thrombophlebitis",
                    "criterion": "thrombophlebitis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "tendency to thrombosis",
                    "criterion": "tendency to thrombosis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* severe lung disease, dyspnea at rest, pleural effusion",
            "criterions": [
                {
                    "exact_snippets": "severe lung disease",
                    "criterion": "lung disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        }
                    ]
                },
                {
                    "exact_snippets": "dyspnea at rest",
                    "criterion": "dyspnea",
                    "requirements": [
                        {
                            "requirement_type": "condition",
                            "expected_value": "at rest"
                        }
                    ]
                },
                {
                    "exact_snippets": "pleural effusion",
                    "criterion": "pleural effusion",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* cardiovascular insufficiency, ejection fraction of the heart <40%",
            "criterions": [
                {
                    "exact_snippets": "cardiovascular insufficiency",
                    "criterion": "cardiovascular insufficiency",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "ejection fraction of the heart <40%",
                    "criterion": "ejection fraction of the heart",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<",
                                "value": 40,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* sensory neuropathy of the 1st degree of any etiology",
            "criterions": [
                {
                    "exact_snippets": "sensory neuropathy of the 1st degree of any etiology",
                    "criterion": "sensory neuropathy",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "1st degree"
                        },
                        {
                            "requirement_type": "etiology",
                            "expected_value": "any"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* uncontrolled infections",
            "criterions": [
                {
                    "exact_snippets": "uncontrolled infections",
                    "criterion": "infections",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* persons from the category of \"vulnerable patients\" (homeless, military personnel, incapacitated, patients in emergency conditions, other persons who may be subjected to pressure);",
            "criterions": [
                {
                    "exact_snippets": "homeless",
                    "criterion": "vulnerable patient category",
                    "requirements": [
                        {
                            "requirement_type": "category",
                            "expected_value": "homeless"
                        }
                    ]
                },
                {
                    "exact_snippets": "military personnel",
                    "criterion": "vulnerable patient category",
                    "requirements": [
                        {
                            "requirement_type": "category",
                            "expected_value": "military personnel"
                        }
                    ]
                },
                {
                    "exact_snippets": "incapacitated",
                    "criterion": "vulnerable patient category",
                    "requirements": [
                        {
                            "requirement_type": "category",
                            "expected_value": "incapacitated"
                        }
                    ]
                },
                {
                    "exact_snippets": "patients in emergency conditions",
                    "criterion": "vulnerable patient category",
                    "requirements": [
                        {
                            "requirement_type": "category",
                            "expected_value": "patients in emergency conditions"
                        }
                    ]
                },
                {
                    "exact_snippets": "other persons who may be subjected to pressure",
                    "criterion": "vulnerable patient category",
                    "requirements": [
                        {
                            "requirement_type": "category",
                            "expected_value": "other persons who may be subjected to pressure"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Allergy in history and during screening (drug, pollen, etc.);",
            "criterions": [
                {
                    "exact_snippets": "Allergy in history",
                    "criterion": "allergy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Allergy ... during screening",
                    "criterion": "allergy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* participation in any other clinical trial;",
            "criterions": [
                {
                    "exact_snippets": "participation in any other clinical trial",
                    "criterion": "participation in other clinical trial",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* hypersensitivity to arsenic;",
            "criterions": [
                {
                    "exact_snippets": "hypersensitivity to arsenic",
                    "criterion": "hypersensitivity to arsenic",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* individual intolerance to ascorbic acid;",
            "criterions": [
                {
                    "exact_snippets": "individual intolerance to ascorbic acid",
                    "criterion": "intolerance to ascorbic acid",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* thrombophlebitis and thrombosis, a tendency to thrombosis in history;",
            "criterions": [
                {
                    "exact_snippets": "thrombophlebitis",
                    "criterion": "thrombophlebitis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "thrombosis",
                    "criterion": "thrombosis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "a tendency to thrombosis in history",
                    "criterion": "tendency to thrombosis",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* increased blood clotting and pathologies associated with this deviation;",
            "criterions": [
                {
                    "exact_snippets": "increased blood clotting",
                    "criterion": "blood clotting",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "increased"
                        }
                    ]
                },
                {
                    "exact_snippets": "pathologies associated with this deviation",
                    "criterion": "pathologies associated with increased blood clotting",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* diabetes;",
            "criterions": [
                {
                    "exact_snippets": "diabetes",
                    "criterion": "diabetes",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* nephrolithiasis or nephrolithiasis;",
            "criterions": [
                {
                    "exact_snippets": "nephrolithiasis",
                    "criterion": "nephrolithiasis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* the patient does not agree to perform the procedures required by the protocol and is unable to adhere to the schedule of procedures.",
            "criterions": [
                {
                    "exact_snippets": "the patient does not agree to perform the procedures required by the protocol",
                    "criterion": "agreement to perform procedures",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "unable to adhere to the schedule of procedures",
                    "criterion": "ability to adhere to schedule",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* if the patients have any other laboratory or other abnormalities, in the opinion of the Investigator, that can harm the patients and the results of the study.",
            "criterions": [
                {
                    "exact_snippets": "any other laboratory or other abnormalities",
                    "criterion": "laboratory or other abnormalities",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "for both groups (30 patients, considering 20% decrease from the study):",
            "criterions": [
                {
                    "exact_snippets": "30 patients",
                    "criterion": "number of patients",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "=",
                                "value": 30,
                                "unit": "patients"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "20% decrease from the study",
                    "criterion": "decrease from the study",
                    "requirements": [
                        {
                            "requirement_type": "percentage",
                            "expected_value": {
                                "operator": "=",
                                "value": 20,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* informed consent to participate in the study",
            "criterions": [
                {
                    "exact_snippets": "informed consent to participate in the study",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* patients of the second clinical group with advanced/metastatic colorectal cancer",
            "criterions": [
                {
                    "exact_snippets": "patients of the second clinical group",
                    "criterion": "clinical group",
                    "requirements": [
                        {
                            "requirement_type": "group number",
                            "expected_value": "second"
                        }
                    ]
                },
                {
                    "exact_snippets": "advanced/metastatic colorectal cancer",
                    "criterion": "colorectal cancer",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "advanced",
                                "metastatic"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients must have previously received at least 3 lines of standard drug therapy, including those with the use of targeted drugs, who have exhausted the possibilities of using specialized drugs, as part of the recommendations of colorectal cancer treatment protocols - the presence of \"+\" KRAS / NRAS status of the primary tumor, or metastatic focus (determined in exon 2, codons 12, 13, 61)",
            "criterions": [
                {
                    "exact_snippets": "previously received at least 3 lines of standard drug therapy",
                    "criterion": "lines of standard drug therapy",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "lines"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "use of targeted drugs",
                    "criterion": "use of targeted drugs",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "exhausted the possibilities of using specialized drugs",
                    "criterion": "use of specialized drugs",
                    "requirements": [
                        {
                            "requirement_type": "exhaustion",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "presence of \"+\" KRAS / NRAS status",
                    "criterion": "KRAS / NRAS status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": "+"
                        }
                    ]
                },
                {
                    "exact_snippets": "primary tumor, or metastatic focus (determined in exon 2, codons 12, 13, 61)",
                    "criterion": "KRAS / NRAS mutation location",
                    "requirements": [
                        {
                            "requirement_type": "location",
                            "expected_value": [
                                "primary tumor",
                                "metastatic focus"
                            ]
                        },
                        {
                            "requirement_type": "exon",
                            "expected_value": "2"
                        },
                        {
                            "requirement_type": "codons",
                            "expected_value": [
                                "12",
                                "13",
                                "61"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* ≥1 measurable lesion defined by RECIST v1.1",
            "criterions": [
                {
                    "exact_snippets": "≥1 measurable lesion defined by RECIST v1.1",
                    "criterion": "measurable lesion",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "N/A"
                            }
                        },
                        {
                            "requirement_type": "definition",
                            "expected_value": "RECIST v1.1"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* ECOG PS 0.1 or 2",
            "criterions": [
                {
                    "exact_snippets": "ECOG PS 0.1 or 2",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": [
                                "0",
                                "1",
                                "2"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* age up to 18 years",
            "criterions": [
                {
                    "exact_snippets": "age up to 18 years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "maximum",
                            "expected_value": {
                                "operator": "<=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* patients with an autoimmune disease or with a medical diagnosis requiring systemic immunosuppression",
            "criterions": [
                {
                    "exact_snippets": "patients with an autoimmune disease",
                    "criterion": "autoimmune disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "medical diagnosis requiring systemic immunosuppression",
                    "criterion": "systemic immunosuppression",
                    "requirements": [
                        {
                            "requirement_type": "necessity",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* decompensated diabetes mellitus",
            "criterions": [
                {
                    "exact_snippets": "decompensated diabetes mellitus",
                    "criterion": "diabetes mellitus",
                    "requirements": [
                        {
                            "requirement_type": "compensation status",
                            "expected_value": "decompensated"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* renal failure, urolithiasis",
            "criterions": [
                {
                    "exact_snippets": "renal failure",
                    "criterion": "renal failure",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "urolithiasis",
                    "criterion": "urolithiasis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* thrombophlebitis, tendency to thrombosis",
            "criterions": [
                {
                    "exact_snippets": "thrombophlebitis",
                    "criterion": "thrombophlebitis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "tendency to thrombosis",
                    "criterion": "tendency to thrombosis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* severe lung disease, dyspnea at rest, pleural effusion",
            "criterions": [
                {
                    "exact_snippets": "severe lung disease",
                    "criterion": "lung disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        }
                    ]
                },
                {
                    "exact_snippets": "dyspnea at rest",
                    "criterion": "dyspnea",
                    "requirements": [
                        {
                            "requirement_type": "condition",
                            "expected_value": "at rest"
                        }
                    ]
                },
                {
                    "exact_snippets": "pleural effusion",
                    "criterion": "pleural effusion",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* cardiovascular insufficiency, ejection fraction of the heart <40%",
            "criterions": [
                {
                    "exact_snippets": "cardiovascular insufficiency",
                    "criterion": "cardiovascular insufficiency",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "ejection fraction of the heart <40%",
                    "criterion": "ejection fraction of the heart",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<",
                                "value": 40,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* sensory neuropathy of the 1st degree of any etiology",
            "criterions": [
                {
                    "exact_snippets": "sensory neuropathy of the 1st degree",
                    "criterion": "sensory neuropathy",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "1st degree"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* uncontrolled infections",
            "criterions": [
                {
                    "exact_snippets": "uncontrolled infections",
                    "criterion": "infections",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* persons from the category of \"vulnerable patients\" (homeless, military personnel, incapacitated, patients in emergency conditions, other persons who may be subjected to pressure);",
            "criterions": [
                {
                    "exact_snippets": "category of \"vulnerable patients\" (homeless, military personnel, incapacitated, patients in emergency conditions, other persons who may be subjected to pressure)",
                    "criterion": "vulnerable patient category",
                    "requirements": [
                        {
                            "requirement_type": "categories",
                            "expected_value": [
                                "homeless",
                                "military personnel",
                                "incapacitated",
                                "patients in emergency conditions",
                                "other persons who may be subjected to pressure"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Allergy in history and during screening (drug, pollen, etc.);",
            "criterions": [
                {
                    "exact_snippets": "Allergy in history",
                    "criterion": "allergy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "during screening (drug, pollen, etc.)",
                    "criterion": "allergy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* participation in any other clinical trial;",
            "criterions": [
                {
                    "exact_snippets": "participation in any other clinical trial",
                    "criterion": "participation in other clinical trials",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* hypersensitivity to arsenic;",
            "criterions": [
                {
                    "exact_snippets": "hypersensitivity to arsenic",
                    "criterion": "hypersensitivity to arsenic",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* individual intolerance to ascorbic acid;",
            "criterions": [
                {
                    "exact_snippets": "individual intolerance to ascorbic acid",
                    "criterion": "intolerance to ascorbic acid",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* thrombophlebitis and thrombosis, a tendency to thrombosis in history;",
            "criterions": [
                {
                    "exact_snippets": "thrombophlebitis",
                    "criterion": "thrombophlebitis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "thrombosis",
                    "criterion": "thrombosis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "a tendency to thrombosis in history",
                    "criterion": "tendency to thrombosis",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* increased blood clotting and pathologies associated with this deviation;",
            "criterions": [
                {
                    "exact_snippets": "increased blood clotting",
                    "criterion": "blood clotting",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "increased"
                        }
                    ]
                },
                {
                    "exact_snippets": "pathologies associated with this deviation",
                    "criterion": "pathologies associated with increased blood clotting",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* diabetes;",
            "criterions": [
                {
                    "exact_snippets": "diabetes",
                    "criterion": "diabetes",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* nephrolithiasis or nephrolithiasis;",
            "criterions": [
                {
                    "exact_snippets": "nephrolithiasis",
                    "criterion": "nephrolithiasis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* the patient does not agree to perform the procedures required by the protocol and is unable to adhere to the schedule of procedures.",
            "criterions": [
                {
                    "exact_snippets": "the patient does not agree to perform the procedures required by the protocol",
                    "criterion": "agreement to perform procedures",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "unable to adhere to the schedule of procedures",
                    "criterion": "ability to adhere to schedule",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* if the patients have any other laboratory or other abnormalities, in the opinion of the Investigator, that can harm the patients and the results of the study.",
            "criterions": [
                {
                    "exact_snippets": "any other laboratory or other abnormalities",
                    "criterion": "laboratory or other abnormalities",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": [
        {
            "line": "INCLUSION CRITERIA:",
            "criterions": []
        },
        {
            "line": "EXCLUSION CRITERIA:",
            "criterions": []
        },
        {
            "line": "Phase II:",
            "criterions": []
        },
        {
            "line": "INCLUSION CRITERIA:",
            "criterions": []
        },
        {
            "line": "EXCLUSION CRITERIA:",
            "criterions": []
        }
    ]
}