{
    "info": {
        "nct_id": "NCT03146962",
        "official_title": "A Phase II Study of High Dose Vitamin C Intravenous Infusion in Patients With Resectable or Metastatic Solid Tumor Malignancies",
        "inclusion_criteria": "Healthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Patients with uncontrolled intercurrent illness including, but not limited to uncontrolled infection, symptomatic congestive heart failure (NYHA class III and IV), uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements (Appendix B: New York Heart Association (NYHA) Classifications).\n* Patients with active heart disease including myocardial infarction within previous 3 months, symptomatic coronary artery disease, arrhythmias not controlled by medication, unstable angina pectoris, or uncontrolled congestive heart failure (NYHA class III and IV) (Appendix B: New York Heart Association (NYHA) Classifications).\n* Patients who have received an investigational drug within 21 days of the first dose of study drug.\n* Patients who are pregnant or lactating.\n* Patients who are known to be positive for the human immunodeficiency virus (HIV). The effect of Vitamin C on HIV medications is unknown. Note: HIV testing is not required for eligibility, but if performed previously and was positive, the patient is ineligible for the study.\n* Patient who are receiving drugs which are known to interact with Vitamin C, potential risk and eligibility will be evaluated individually by the investigator. a. Most of the known interactions with vitamin C are from oral use and acidification of the stomach lining. There are few known interactions with high dose intravenous vitamin C. We recommend not using deferoxamine as there may be an association with ventricular dysfunction (unknown mechanism).\n* Patients who have uncontrolled or severe hyponatremia, hypernatremia, SIADH, hypokalemia, hyperkalemia, hypomagnesemia, or hypermagnesemia\n* Patients who have uncontrolled or severe coagulopathies or a history of clinically significant bleeding within the past 6 months, such as hemoptysis, epistaxis, hematochezia, hematuria, or gastrointestinal bleeding.\n* Patients who require therapeutic doses of warfarin\n* Patients who have uncontrolled seizure disorder, ascites, iron overload, edema, or dehydration.\n* Patients who have glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis, or other conditions predisposing patient to hemolysis.\n* Patients who have a known history of recurrent oxalate renal calculi or multiple oxalate.",
        "miscellaneous_criteria": "Inclusion Criteria\n\n* Male or female ≥ 18 years of age.\n* Patients with histologically proven early stage or locally advanced colorectal adenocarcinoma, lung cancer or pancreatic cancer, who are eligible for resection (cohort A).\n* Patients with inoperable, metastatic extended RAS (e.g. KRAS or NRAS) or BRAF mutant colorectal adenocarcinoma, lung cancer and pancreatic cancer, or other solid tumor, who have received at least 1 line of treatment for metastatic disease (cohort B).\n* Patients with metastatic cancer with an extended RAS (e.g. KRAS or NRAS) or BRAF mutation with liver metastases amenable to Y90 radioembolization (cohort C).\n* ECOG performance status 0-1.\n* Life expectancy of at least 6 months.\n* All women of child-bearing potential and all sexually active male patients must agree to use effective contraception."
    },
    "inclusion_lines": [
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have minimum age of 18 Years",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 18 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "* Patients with uncontrolled intercurrent illness including, but not limited to uncontrolled infection, symptomatic congestive heart failure (NYHA class III and IV), uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements (Appendix B: New York Heart Association (NYHA) Classifications).",
            "criterions": [
                {
                    "exact_snippets": "uncontrolled intercurrent illness including, but not limited to uncontrolled infection",
                    "criterion": "uncontrolled infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled intercurrent illness including, but not limited to ... symptomatic congestive heart failure (NYHA class III and IV)",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "NYHA class III",
                                "NYHA class IV"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled intercurrent illness including, but not limited to ... uncontrolled cardiac arrhythmia",
                    "criterion": "cardiac arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled intercurrent illness including, but not limited to ... psychiatric illness/social situations that would limit compliance with study requirements",
                    "criterion": "psychiatric illness/social situations",
                    "requirements": [
                        {
                            "requirement_type": "impact on compliance",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with active heart disease including myocardial infarction within previous 3 months, symptomatic coronary artery disease, arrhythmias not controlled by medication, unstable angina pectoris, or uncontrolled congestive heart failure (NYHA class III and IV) (Appendix B: New York Heart Association (NYHA) Classifications).",
            "criterions": [
                {
                    "exact_snippets": "active heart disease including myocardial infarction within previous 3 months",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "active heart disease including ... symptomatic coronary artery disease",
                    "criterion": "symptomatic coronary artery disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "active heart disease including ... arrhythmias not controlled by medication",
                    "criterion": "arrhythmias",
                    "requirements": [
                        {
                            "requirement_type": "control by medication",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "active heart disease including ... unstable angina pectoris",
                    "criterion": "unstable angina pectoris",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "active heart disease including ... uncontrolled congestive heart failure (NYHA class III and IV)",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "NYHA class",
                            "expected_value": [
                                "III",
                                "IV"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who have received an investigational drug within 21 days of the first dose of study drug.",
            "criterions": [
                {
                    "exact_snippets": "Patients who have received an investigational drug within 21 days",
                    "criterion": "investigational drug",
                    "requirements": [
                        {
                            "requirement_type": "time since last dose",
                            "expected_value": {
                                "operator": "<=",
                                "value": 21,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who are pregnant or lactating.",
            "criterions": [
                {
                    "exact_snippets": "Patients who are pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "lactating",
                    "criterion": "lactation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who are known to be positive for the human immunodeficiency virus (HIV). The effect of Vitamin C on HIV medications is unknown. Note: HIV testing is not required for eligibility, but if performed previously and was positive, the patient is ineligible for the study.",
            "criterions": [
                {
                    "exact_snippets": "Patients who are known to be positive for the human immunodeficiency virus (HIV) ... if performed previously and was positive, the patient is ineligible for the study.",
                    "criterion": "HIV status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": "positive"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patient who are receiving drugs which are known to interact with Vitamin C, potential risk and eligibility will be evaluated individually by the investigator. a. Most of the known interactions with vitamin C are from oral use and acidification of the stomach lining. There are few known interactions with high dose intravenous vitamin C. We recommend not using deferoxamine as there may be an association with ventricular dysfunction (unknown mechanism).",
            "criterions": [
                {
                    "exact_snippets": "Patient who are receiving drugs which are known to interact with Vitamin C",
                    "criterion": "drug interaction with Vitamin C",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "not using deferoxamine",
                    "criterion": "use of deferoxamine",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who have uncontrolled or severe hyponatremia, hypernatremia, SIADH, hypokalemia, hyperkalemia, hypomagnesemia, or hypermagnesemia",
            "criterions": [
                {
                    "exact_snippets": "uncontrolled or severe hyponatremia",
                    "criterion": "hyponatremia",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "uncontrolled",
                                "severe"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled or severe ... hypernatremia",
                    "criterion": "hypernatremia",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "uncontrolled",
                                "severe"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled or severe ... SIADH",
                    "criterion": "SIADH",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "uncontrolled",
                                "severe"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled or severe ... hypokalemia",
                    "criterion": "hypokalemia",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "uncontrolled",
                                "severe"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled or severe ... hyperkalemia",
                    "criterion": "hyperkalemia",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "uncontrolled",
                                "severe"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled or severe ... hypomagnesemia",
                    "criterion": "hypomagnesemia",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "uncontrolled",
                                "severe"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled or severe ... hypermagnesemia",
                    "criterion": "hypermagnesemia",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "uncontrolled",
                                "severe"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who have uncontrolled or severe coagulopathies or a history of clinically significant bleeding within the past 6 months, such as hemoptysis, epistaxis, hematochezia, hematuria, or gastrointestinal bleeding.",
            "criterions": [
                {
                    "exact_snippets": "uncontrolled or severe coagulopathies",
                    "criterion": "coagulopathies",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "uncontrolled",
                                "severe"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "history of clinically significant bleeding within the past 6 months",
                    "criterion": "clinically significant bleeding",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within the past 6 months"
                        }
                    ]
                },
                {
                    "exact_snippets": "hemoptysis",
                    "criterion": "hemoptysis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "epistaxis",
                    "criterion": "epistaxis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "hematochezia",
                    "criterion": "hematochezia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "hematuria",
                    "criterion": "hematuria",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "gastrointestinal bleeding",
                    "criterion": "gastrointestinal bleeding",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who require therapeutic doses of warfarin",
            "criterions": [
                {
                    "exact_snippets": "require therapeutic doses of warfarin",
                    "criterion": "warfarin",
                    "requirements": [
                        {
                            "requirement_type": "dosage",
                            "expected_value": "therapeutic"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who have uncontrolled seizure disorder, ascites, iron overload, edema, or dehydration.",
            "criterions": [
                {
                    "exact_snippets": "uncontrolled seizure disorder",
                    "criterion": "seizure disorder",
                    "requirements": [
                        {
                            "requirement_type": "control status",
                            "expected_value": "uncontrolled"
                        }
                    ]
                },
                {
                    "exact_snippets": "ascites",
                    "criterion": "ascites",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "iron overload",
                    "criterion": "iron overload",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "edema",
                    "criterion": "edema",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "dehydration",
                    "criterion": "dehydration",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who have glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis, or other conditions predisposing patient to hemolysis.",
            "criterions": [
                {
                    "exact_snippets": "glucose-6-phosphate dehydrogenase (G6PD) deficiency",
                    "criterion": "glucose-6-phosphate dehydrogenase (G6PD) deficiency",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "hereditary spherocytosis",
                    "criterion": "hereditary spherocytosis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "conditions predisposing patient to hemolysis",
                    "criterion": "conditions predisposing to hemolysis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients who have a known history of recurrent oxalate renal calculi or multiple oxalate.",
            "criterions": [
                {
                    "exact_snippets": "known history of recurrent oxalate renal calculi",
                    "criterion": "oxalate renal calculi",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": "recurrent"
                        }
                    ]
                },
                {
                    "exact_snippets": "multiple oxalate",
                    "criterion": "oxalate",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": "multiple"
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [
        {
            "line": "* Male or female ≥ 18 years of age.",
            "criterions": [
                {
                    "exact_snippets": "Male or female",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "≥ 18 years of age",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with histologically proven early stage or locally advanced colorectal adenocarcinoma, lung cancer or pancreatic cancer, who are eligible for resection (cohort A).",
            "criterions": [
                {
                    "exact_snippets": "histologically proven",
                    "criterion": "histological proof",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "early stage or locally advanced colorectal adenocarcinoma",
                    "criterion": "colorectal adenocarcinoma",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": [
                                "early stage",
                                "locally advanced"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "lung cancer",
                    "criterion": "lung cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "pancreatic cancer",
                    "criterion": "pancreatic cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "eligible for resection",
                    "criterion": "eligibility for resection",
                    "requirements": [
                        {
                            "requirement_type": "eligibility",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with inoperable, metastatic extended RAS (e.g. KRAS or NRAS) or BRAF mutant colorectal adenocarcinoma, lung cancer and pancreatic cancer, or other solid tumor, who have received at least 1 line of treatment for metastatic disease (cohort B).",
            "criterions": [
                {
                    "exact_snippets": "inoperable, metastatic extended RAS (e.g. KRAS or NRAS) or BRAF mutant colorectal adenocarcinoma",
                    "criterion": "colorectal adenocarcinoma",
                    "requirements": [
                        {
                            "requirement_type": "operability",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "metastatic",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "mutation",
                            "expected_value": [
                                "extended RAS",
                                "BRAF"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "lung cancer",
                    "criterion": "lung cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "pancreatic cancer",
                    "criterion": "pancreatic cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "other solid tumor",
                    "criterion": "other solid tumor",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "at least 1 line of treatment for metastatic disease",
                    "criterion": "treatment for metastatic disease",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "line"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with metastatic cancer with an extended RAS (e.g. KRAS or NRAS) or BRAF mutation with liver metastases amenable to Y90 radioembolization (cohort C).",
            "criterions": [
                {
                    "exact_snippets": "metastatic cancer",
                    "criterion": "metastatic cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "extended RAS (e.g. KRAS or NRAS) or BRAF mutation",
                    "criterion": "extended RAS or BRAF mutation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "liver metastases",
                    "criterion": "liver metastases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "amenable to Y90 radioembolization",
                    "criterion": "amenability to Y90 radioembolization",
                    "requirements": [
                        {
                            "requirement_type": "amenability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* ECOG performance status 0-1.",
            "criterions": [
                {
                    "exact_snippets": "ECOG performance status 0-1",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 1,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Life expectancy of at least 6 months.",
            "criterions": [
                {
                    "exact_snippets": "Life expectancy of at least 6 months.",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* All women of child-bearing potential and all sexually active male patients must agree to use effective contraception.",
            "criterions": [
                {
                    "exact_snippets": "All women of child-bearing potential",
                    "criterion": "women of child-bearing potential",
                    "requirements": [
                        {
                            "requirement_type": "agreement to use contraception",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "all sexually active male patients",
                    "criterion": "sexually active male patients",
                    "requirements": [
                        {
                            "requirement_type": "agreement to use contraception",
                            "expected_value": true
                        }
                    ]
                }
            ]
        }
    ],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": [
        {
            "line": "Inclusion Criteria",
            "criterions": []
        }
    ]
}