{
    "info": {
        "nct_id": "NCT03475589",
        "official_title": "A Clinical Study Investigating Adverse Drug Reactions and Their Biomarker Correlations in Stage IV Cancer Patients Following Individualized Therapy of Apatinib",
        "inclusion_criteria": "1. Age of 18 and over, male or female;\n2. Patients with histologically confirmed advanced (stage IV) gastric cancer, NSCLC, breast cancer or ovarian cancer, who choose monotherapy of oral vascular targeting drug (apatinib) due to intolerability or inappropriateness of other therapies;\n3. Presence of measurable lesions (≥10mm on spiral CT scan) subject to RECIST 1.1;\n4. Blood pressured controlled at 150/100 mHg following drug administration;\n5. An ECOG PS score of between 0 and 1;\n6. Findings of hematology and laboratory tests at the baseline that meet the following criteria:\n\n   Hemoglobin ≥80g/L; Absolute neutrophil count (ANC) ≥1.5×10^9/L; Platelets ≥90×10^9/L; ALT/AST ≤ 2.5×ULN; or ALT/AST ≤ 5×ULN for patients with hepatic metastases; Serum total bilirubin ≤1.5×ULN; Serum urea nitrogen and creatinine ≤ 1.5×ULN; Serum albumin ≥30g/L; Coagulation function (INR≤1.5, APTT≤1.5 ULN);\n7. A life expectancy of at least 3 months;\n8. Subjects who volunteer to participate in this study and have signed the Informed Consent Form (ICF), with good compliance with treatment and follow-up.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "1. Confirmed allergy to apatinin and or its excipients;\n2. Hypertension (high blood pressure) that can not be controlled by drugs;\n3. A history of active hemorragge, ulcer, intestinal perforation, intestinal obstruction, or major surgery no older than 30 days;\n4. NYHA III-IV heart function, or severe hepatic or renal insufficiency (Grade 4);\n5. Presence of multiple factors that affect oral medications, such as difficulty swallowing, nausea, vomiting, chronic diarrhea and intestinal obstruction;\n6. Pregnant or lactating women, or women of child-bearing potential who have planned a pregnancy, or male and female patients who do not agree to practice adequate contraception during this study;\n7. Patients who have a history of psychotropics abuse and can not quit, or who have mental disorders;\n8. Participation in other drug clinical trial within the last 4 weeks;\n9. Prior therapy with VEGFR inhibitors such as sorafenib and sunitinib;\n10. Presence of comorbidities that seriously affect the patient's safety or ability to complete the study, in the investigator's judgment;\n11. Patients who can not tolerate apatinib treatment as judged by the investigator depending on the their medical history;\n12. Patients that are considered ineligible for this study by the investigator.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Age of 18 and over, male or female;",
            "criterions": [
                {
                    "exact_snippets": [
                        "Age of 18 and over"
                    ],
                    "criterion": "age",
                    "requirement_type": "range",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 18
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "male or female"
                    ],
                    "criterion": "gender",
                    "requirement_type": "inclusion",
                    "expected_value": [
                        "male",
                        "female"
                    ]
                }
            ]
        },
        {
            "line": "2. Patients with histologically confirmed advanced (stage IV) gastric cancer, NSCLC, breast cancer or ovarian cancer, who choose monotherapy of oral vascular targeting drug (apatinib) due to intolerability or inappropriateness of other therapies;",
            "criterions": [
                {
                    "exact_snippets": [
                        "histologically confirmed"
                    ],
                    "criterion": "cancer diagnosis",
                    "requirement_type": "confirmation method",
                    "expected_value": "histological"
                },
                {
                    "exact_snippets": [
                        "advanced (stage IV) gastric cancer"
                    ],
                    "criterion": "gastric cancer",
                    "requirement_type": "stage",
                    "expected_value": "IV"
                },
                {
                    "exact_snippets": [
                        "NSCLC"
                    ],
                    "criterion": "NSCLC",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "breast cancer"
                    ],
                    "criterion": "breast cancer",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "ovarian cancer"
                    ],
                    "criterion": "ovarian cancer",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "choose monotherapy of oral vascular targeting drug (apatinib)"
                    ],
                    "criterion": "treatment choice",
                    "requirement_type": "specific treatment",
                    "expected_value": "monotherapy of oral vascular targeting drug (apatinib)"
                },
                {
                    "exact_snippets": [
                        "intolerability or inappropriateness of other therapies"
                    ],
                    "criterion": "other therapies",
                    "requirement_type": "tolerability or appropriateness",
                    "expected_value": false
                }
            ]
        },
        {
            "line": "3. Presence of measurable lesions (≥10mm on spiral CT scan) subject to RECIST 1.1;",
            "criterions": [
                {
                    "exact_snippets": [
                        "Presence of measurable lesions"
                    ],
                    "criterion": "measurable lesions",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "measurable lesions (≥10mm on spiral CT scan)"
                    ],
                    "criterion": "measurable lesions",
                    "requirement_type": "size",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 10
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "subject to RECIST 1.1"
                    ],
                    "criterion": "RECIST 1.1",
                    "requirement_type": "compliance",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "4. Blood pressured controlled at 150/100 mHg following drug administration;",
            "criterions": [
                {
                    "exact_snippets": [
                        "Blood pressured controlled at 150/100 mHg"
                    ],
                    "criterion": "blood pressure",
                    "requirement_type": "control",
                    "expected_value": "150/100 mHg"
                }
            ]
        },
        {
            "line": "5. An ECOG PS score of between 0 and 1;",
            "criterions": [
                {
                    "exact_snippets": [
                        "ECOG PS score",
                        "between 0 and 1"
                    ],
                    "criterion": "ECOG PS score",
                    "requirement_type": "range",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 0
                            },
                            {
                                "operator": "<=",
                                "value": 1
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "6. Findings of hematology and laboratory tests at the baseline that meet the following criteria:",
            "criterions": [
                {
                    "exact_snippets": [
                        "hematology and laboratory tests"
                    ],
                    "criterion": "hematology and laboratory tests",
                    "requirement_type": "findings",
                    "expected_value": "meet the following criteria"
                }
            ]
        },
        {
            "line": "Hemoglobin ≥80g/L; Absolute neutrophil count (ANC) ≥1.5×10^9/L; Platelets ≥90×10^9/L; ALT/AST ≤ 2.5×ULN; or ALT/AST ≤ 5×ULN for patients with hepatic metastases; Serum total bilirubin ≤1.5×ULN; Serum urea nitrogen and creatinine ≤ 1.5×ULN; Serum albumin ≥30g/L; Coagulation function (INR≤1.5, APTT≤1.5 ULN);",
            "criterions": [
                {
                    "exact_snippets": [
                        "Hemoglobin ≥80g/L"
                    ],
                    "criterion": "hemoglobin",
                    "requirement_type": "level",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 80
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "Absolute neutrophil count (ANC) ≥1.5×10^9/L"
                    ],
                    "criterion": "absolute neutrophil count",
                    "requirement_type": "level",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 1.5
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "Platelets ≥90×10^9/L"
                    ],
                    "criterion": "platelets",
                    "requirement_type": "level",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 90
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "ALT/AST ≤ 2.5×ULN"
                    ],
                    "criterion": "ALT/AST",
                    "requirement_type": "level",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 2.5
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "ALT/AST ≤ 5×ULN",
                        "for patients with hepatic metastases"
                    ],
                    "criterion": "ALT/AST",
                    "requirement_type": "level",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 5
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "Serum total bilirubin ≤1.5×ULN"
                    ],
                    "criterion": "serum total bilirubin",
                    "requirement_type": "level",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 1.5
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "Serum urea nitrogen and creatinine ≤ 1.5×ULN"
                    ],
                    "criterion": "serum urea nitrogen and creatinine",
                    "requirement_type": "level",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 1.5
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "Serum albumin ≥30g/L"
                    ],
                    "criterion": "serum albumin",
                    "requirement_type": "level",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 30
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "Coagulation function (INR≤1.5, APTT≤1.5 ULN)"
                    ],
                    "criterion": "coagulation function",
                    "requirement_type": "level",
                    "expected_value": "INR≤1.5, APTT≤1.5 ULN"
                }
            ]
        },
        {
            "line": "7. A life expectancy of at least 3 months;",
            "criterions": [
                {
                    "exact_snippets": [
                        "life expectancy",
                        "at least 3 months"
                    ],
                    "criterion": "life expectancy",
                    "requirement_type": "duration",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 3
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "8. Subjects who volunteer to participate in this study and have signed the Informed Consent Form (ICF), with good compliance with treatment and follow-up.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Subjects who volunteer to participate"
                    ],
                    "criterion": "volunteer status",
                    "requirement_type": "participation",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "have signed the Informed Consent Form (ICF)"
                    ],
                    "criterion": "Informed Consent Form",
                    "requirement_type": "signed",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "good compliance with treatment and follow-up"
                    ],
                    "criterion": "compliance",
                    "requirement_type": "quality",
                    "expected_value": "good"
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": [
                        "Healthy volunteers allowed"
                    ],
                    "criterion": "healthy volunteers",
                    "requirement_type": "participation",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "Must have minimum age of 18 Years",
            "criterions": [
                {
                    "exact_snippets": [
                        "minimum age of 18 Years"
                    ],
                    "criterion": "age",
                    "requirement_type": "minimum",
                    "expected_value": {
                        "operator": ">=",
                        "value": 18
                    }
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "1. Confirmed allergy to apatinin and or its excipients;",
            "criterions": [
                {
                    "exact_snippets": [
                        "Confirmed allergy to apatinin"
                    ],
                    "criterion": "allergy",
                    "requirement_type": "presence",
                    "expected_value": "apatinin"
                },
                {
                    "exact_snippets": [
                        "Confirmed allergy to",
                        "its excipients"
                    ],
                    "criterion": "allergy",
                    "requirement_type": "presence",
                    "expected_value": "excipients of apatinin"
                }
            ]
        },
        {
            "line": "2. Hypertension (high blood pressure) that can not be controlled by drugs;",
            "criterions": [
                {
                    "exact_snippets": [
                        "Hypertension (high blood pressure)"
                    ],
                    "criterion": "hypertension",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "can not be controlled by drugs"
                    ],
                    "criterion": "hypertension",
                    "requirement_type": "control by drugs",
                    "expected_value": false
                }
            ]
        },
        {
            "line": "3. A history of active hemorragge, ulcer, intestinal perforation, intestinal obstruction, or major surgery no older than 30 days;",
            "criterions": [
                {
                    "exact_snippets": [
                        "A history of active hemorragge"
                    ],
                    "criterion": "active hemorrhage",
                    "requirement_type": "history",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "A history of",
                        "ulcer"
                    ],
                    "criterion": "ulcer",
                    "requirement_type": "history",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "A history of",
                        "intestinal perforation"
                    ],
                    "criterion": "intestinal perforation",
                    "requirement_type": "history",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "A history of",
                        "intestinal obstruction"
                    ],
                    "criterion": "intestinal obstruction",
                    "requirement_type": "history",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "A history of",
                        "major surgery no older than 30 days"
                    ],
                    "criterion": "major surgery",
                    "requirement_type": "history",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 30
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "4. NYHA III-IV heart function, or severe hepatic or renal insufficiency (Grade 4);",
            "criterions": [
                {
                    "exact_snippets": [
                        "NYHA III-IV heart function"
                    ],
                    "criterion": "NYHA heart function",
                    "requirement_type": "severity",
                    "expected_value": [
                        "III",
                        "IV"
                    ]
                },
                {
                    "exact_snippets": [
                        "severe hepatic",
                        "insufficiency (Grade 4)"
                    ],
                    "criterion": "hepatic insufficiency",
                    "requirement_type": "severity",
                    "expected_value": "Grade 4"
                },
                {
                    "exact_snippets": [
                        "severe",
                        "renal insufficiency (Grade 4)"
                    ],
                    "criterion": "renal insufficiency",
                    "requirement_type": "severity",
                    "expected_value": "Grade 4"
                }
            ]
        },
        {
            "line": "5. Presence of multiple factors that affect oral medications, such as difficulty swallowing, nausea, vomiting, chronic diarrhea and intestinal obstruction;",
            "criterions": [
                {
                    "exact_snippets": [
                        "difficulty swallowing"
                    ],
                    "criterion": "difficulty swallowing",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "nausea"
                    ],
                    "criterion": "nausea",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "vomiting"
                    ],
                    "criterion": "vomiting",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "chronic diarrhea"
                    ],
                    "criterion": "chronic diarrhea",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "intestinal obstruction"
                    ],
                    "criterion": "intestinal obstruction",
                    "requirement_type": "presence",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "6. Pregnant or lactating women, or women of child-bearing potential who have planned a pregnancy, or male and female patients who do not agree to practice adequate contraception during this study;",
            "criterions": [
                {
                    "exact_snippets": [
                        "Pregnant"
                    ],
                    "criterion": "pregnancy",
                    "requirement_type": "presence",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "lactating women"
                    ],
                    "criterion": "lactation",
                    "requirement_type": "presence",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "women of child-bearing potential",
                        "planned a pregnancy"
                    ],
                    "criterion": "planned pregnancy",
                    "requirement_type": "intention",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "male and female patients",
                        "do not agree to practice adequate contraception"
                    ],
                    "criterion": "contraception",
                    "requirement_type": "agreement",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "7. Patients who have a history of psychotropics abuse and can not quit, or who have mental disorders;",
            "criterions": [
                {
                    "exact_snippets": [
                        "history of psychotropics abuse"
                    ],
                    "criterion": "psychotropics abuse",
                    "requirement_type": "history",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "can not quit"
                    ],
                    "criterion": "psychotropics abuse",
                    "requirement_type": "ability to quit",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "mental disorders"
                    ],
                    "criterion": "mental disorders",
                    "requirement_type": "presence",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "8. Participation in other drug clinical trial within the last 4 weeks;",
            "criterions": [
                {
                    "exact_snippets": [
                        "Participation in other drug clinical trial"
                    ],
                    "criterion": "participation in other drug clinical trial",
                    "requirement_type": "recency",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 4
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "9. Prior therapy with VEGFR inhibitors such as sorafenib and sunitinib;",
            "criterions": [
                {
                    "exact_snippets": [
                        "Prior therapy with VEGFR inhibitors"
                    ],
                    "criterion": "VEGFR inhibitors",
                    "requirement_type": "prior therapy",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "sorafenib"
                    ],
                    "criterion": "sorafenib",
                    "requirement_type": "prior therapy",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "sunitinib"
                    ],
                    "criterion": "sunitinib",
                    "requirement_type": "prior therapy",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "10. Presence of comorbidities that seriously affect the patient's safety or ability to complete the study, in the investigator's judgment;",
            "criterions": [
                {
                    "exact_snippets": [
                        "Presence of comorbidities that seriously affect the patient's safety or ability to complete the study"
                    ],
                    "criterion": "comorbidities",
                    "requirement_type": "presence",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "11. Patients who can not tolerate apatinib treatment as judged by the investigator depending on the their medical history;",
            "criterions": [
                {
                    "exact_snippets": [
                        "can not tolerate apatinib treatment"
                    ],
                    "criterion": "apatinib treatment",
                    "requirement_type": "tolerance",
                    "expected_value": false
                },
                {
                    "exact_snippets": [
                        "as judged by the investigator depending on the their medical history"
                    ],
                    "criterion": "medical history",
                    "requirement_type": "evaluation",
                    "expected_value": "investigator judgment"
                }
            ]
        },
        {
            "line": "12. Patients that are considered ineligible for this study by the investigator.",
            "criterions": [
                {
                    "exact_snippets": [
                        "considered ineligible for this study by the investigator"
                    ],
                    "criterion": "eligibility",
                    "requirement_type": "determination",
                    "expected_value": "ineligible"
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}