{
    "info": {
        "nct_id": "NCT02601248",
        "official_title": "Single Site, Open-label, Dose Escalation Phase I Study of Theliatinib (HMPL-309) in Patients With Advanced Solid Tumors",
        "inclusion_criteria": "* Histopathology confirmed solid tumors\n* Failed to standard treatment or no standard treatments for uncontrolled, recurrent and/or metastatic advance tumor (whatever previous surgery conditions)\n* Age 18-75\n* Performance status of 0, or 1, and no worse within 7days\n* Life expected >3 months\n* Written informed consent form voluntarily\nHealthy volunteers allowed\nMust have minimum age of 18 Years\nMust have maximum age of 75 Years",
        "exclusion_criteria": "* Lab testing within 1 week before enrolled, AND<1.5×109/L, platelet<75×109/L, or Hb<9g/dL,\n* Total bilirubin≥1.5× the upper limit of normal,\n* Serum creatinine higher than normal range\n* Diastolic pressure≥150mmHg or systolic pressure≥100mmHg whatever anti-hypertension drug used,\n* Serum potassium (whenever potassium implemented) , serum calcium(ionic or albumin-type calcium) or serum magnesium outside normal ranges(whenever implemented)\n* Within previous 4 weeks treated by systemic anti-tumor therapy, or radiotherapy, immune therapy, biological or hormonal therapy, and clinical trials. But exclude the below therapy, Prostate cancer treated by hormonal therapy such as GnRH analogue or antagonist Hormone replacement therapy or oral contraceptive Palliative radiotherapy for bone metastasis within 2 weeks\n* Prior documental evidence of resistance to(epidermal growth factor receptor-tyrosine kinase inhibitors)\n* Unrecovered from any previous therapy related toxicity to≤ CTCAE(Common Toxicity Criteria for Adverse Effects) 0 or 1or unrecovered from any previous surgery\n* Any CNS(central nervous system) metastasis with uncontrolled symptoms\n* Known dysphagia or drug malabsorption\n* Active infections such as acute pneumonia, hepatitis B active period\n* APTT (activated partial thromboplastin time) and/or INR(international normalized ratio), PT≥2 ULN (the upper limit of normal)(not including patients treated by anticoagulation treatment)\n* ocular surface diseases or dry eye syndrome\n* skin disease with obvious symptoms and signs\n* significant cardiovascular disease, including II-IV atrioventricular block, acute myocardial infarction within 6 months, significant angina or Coronary artery bypass graft\n* Known existing interstitial lung disease\n* Female patients who are pregnant or feeding, or childbearing potential patient with pregnant testing positive\n* Any abnormal of clinical and laboratory so that patients unsuitable to attend the trial sine in the opinion of the investigator\n* Patients unable to comply with the protocol since significant psychological or psychogenic abnormal",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Histopathology confirmed solid tumors",
            "criterions": [
                {
                    "exact_snippets": "Histopathology confirmed solid tumors",
                    "criterion": "solid tumors",
                    "requirements": [
                        {
                            "requirement_type": "confirmation method",
                            "expected_value": "histopathology"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Failed to standard treatment or no standard treatments for uncontrolled, recurrent and/or metastatic advance tumor (whatever previous surgery conditions)",
            "criterions": [
                {
                    "exact_snippets": "Failed to standard treatment",
                    "criterion": "standard treatment",
                    "requirements": [
                        {
                            "requirement_type": "response",
                            "expected_value": "failed"
                        }
                    ]
                },
                {
                    "exact_snippets": "no standard treatments",
                    "criterion": "standard treatments",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled, recurrent and/or metastatic advance tumor",
                    "criterion": "tumor",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": "uncontrolled"
                        },
                        {
                            "requirement_type": "recurrence",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "metastasis",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "stage",
                            "expected_value": "advanced"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Age 18-75",
            "criterions": [
                {
                    "exact_snippets": "Age 18-75",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 18,
                                        "unit": "years"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 75,
                                        "unit": "years"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Performance status of 0, or 1, and no worse within 7days",
            "criterions": [
                {
                    "exact_snippets": "Performance status of 0, or 1",
                    "criterion": "performance status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": [
                                "0",
                                "1"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "no worse within 7days",
                    "criterion": "performance status",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": "no worse within 7 days"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Life expected >3 months",
            "criterions": [
                {
                    "exact_snippets": "Life expected >3 months",
                    "criterion": "life expectancy",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": ">",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Written informed consent form voluntarily",
            "criterions": [
                {
                    "exact_snippets": "Written informed consent form voluntarily",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "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": [
        {
            "line": "* Lab testing within 1 week before enrolled, AND<1.5×109/L, platelet<75×109/L, or Hb<9g/dL,",
            "criterions": [
                {
                    "exact_snippets": "Lab testing within 1 week before enrolled",
                    "criterion": "lab testing",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "within 1 week before enrollment"
                        }
                    ]
                },
                {
                    "exact_snippets": "AND<1.5×109/L",
                    "criterion": "neutrophil count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<",
                                "value": 1.5,
                                "unit": "×10^9/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "platelet<75×109/L",
                    "criterion": "platelet count",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<",
                                "value": 75,
                                "unit": "×10^9/L"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Hb<9g/dL",
                    "criterion": "hemoglobin level",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<",
                                "value": 9,
                                "unit": "g/dL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Total bilirubin≥1.5× the upper limit of normal,",
            "criterions": [
                {
                    "exact_snippets": "Total bilirubin≥1.5× the upper limit of normal",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.5,
                                "unit": "× the upper limit of normal"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Serum creatinine higher than normal range",
            "criterions": [
                {
                    "exact_snippets": "Serum creatinine higher than normal range",
                    "criterion": "serum creatinine",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">",
                                "value": 0,
                                "unit": "normal range"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Diastolic pressure≥150mmHg or systolic pressure≥100mmHg whatever anti-hypertension drug used,",
            "criterions": [
                {
                    "exact_snippets": "Diastolic pressure≥150mmHg",
                    "criterion": "diastolic blood pressure",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 150,
                                "unit": "mmHg"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "systolic pressure≥100mmHg",
                    "criterion": "systolic blood pressure",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100,
                                "unit": "mmHg"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Serum potassium (whenever potassium implemented) , serum calcium(ionic or albumin-type calcium) or serum magnesium outside normal ranges(whenever implemented)",
            "criterions": [
                {
                    "exact_snippets": "Serum potassium ... outside normal ranges",
                    "criterion": "serum potassium",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": "normal ranges"
                        }
                    ]
                },
                {
                    "exact_snippets": "serum calcium(ionic or albumin-type calcium) ... outside normal ranges",
                    "criterion": "serum calcium",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": "normal ranges"
                        }
                    ]
                },
                {
                    "exact_snippets": "serum magnesium outside normal ranges",
                    "criterion": "serum magnesium",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": "normal ranges"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Within previous 4 weeks treated by systemic anti-tumor therapy, or radiotherapy, immune therapy, biological or hormonal therapy, and clinical trials. But exclude the below therapy, Prostate cancer treated by hormonal therapy such as GnRH analogue or antagonist Hormone replacement therapy or oral contraceptive Palliative radiotherapy for bone metastasis within 2 weeks",
            "criterions": [
                {
                    "exact_snippets": "Within previous 4 weeks treated by systemic anti-tumor therapy",
                    "criterion": "systemic anti-tumor therapy",
                    "requirements": [
                        {
                            "requirement_type": "treatment timing",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Within previous 4 weeks treated by ... radiotherapy",
                    "criterion": "radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "treatment timing",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Within previous 4 weeks treated by ... immune therapy",
                    "criterion": "immune therapy",
                    "requirements": [
                        {
                            "requirement_type": "treatment timing",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Within previous 4 weeks treated by ... biological ... therapy",
                    "criterion": "biological therapy",
                    "requirements": [
                        {
                            "requirement_type": "treatment timing",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Within previous 4 weeks treated by ... hormonal therapy",
                    "criterion": "hormonal therapy",
                    "requirements": [
                        {
                            "requirement_type": "treatment timing",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Within previous 4 weeks treated by ... clinical trials",
                    "criterion": "participation in clinical trials",
                    "requirements": [
                        {
                            "requirement_type": "participation timing",
                            "expected_value": {
                                "operator": "<=",
                                "value": 4,
                                "unit": "weeks"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Prostate cancer treated by hormonal therapy such as GnRH analogue or antagonist",
                    "criterion": "hormonal therapy for prostate cancer",
                    "requirements": [
                        {
                            "requirement_type": "treatment exclusion",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Hormone replacement therapy or oral contraceptive",
                    "criterion": "hormone replacement therapy or oral contraceptive",
                    "requirements": [
                        {
                            "requirement_type": "treatment exclusion",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Palliative radiotherapy for bone metastasis within 2 weeks",
                    "criterion": "palliative radiotherapy for bone metastasis",
                    "requirements": [
                        {
                            "requirement_type": "treatment timing",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prior documental evidence of resistance to(epidermal growth factor receptor-tyrosine kinase inhibitors)",
            "criterions": [
                {
                    "exact_snippets": "Prior documental evidence of resistance to(epidermal growth factor receptor-tyrosine kinase inhibitors)",
                    "criterion": "resistance to epidermal growth factor receptor-tyrosine kinase inhibitors",
                    "requirements": [
                        {
                            "requirement_type": "evidence",
                            "expected_value": "documental"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Unrecovered from any previous therapy related toxicity to≤ CTCAE(Common Toxicity Criteria for Adverse Effects) 0 or 1or unrecovered from any previous surgery",
            "criterions": [
                {
                    "exact_snippets": "Unrecovered from any previous therapy related toxicity to≤ CTCAE(Common Toxicity Criteria for Adverse Effects) 0 or 1",
                    "criterion": "therapy related toxicity",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": "<=",
                                        "value": 1,
                                        "unit": "CTCAE"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "unrecovered from any previous surgery",
                    "criterion": "recovery from previous surgery",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "unrecovered"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any CNS(central nervous system) metastasis with uncontrolled symptoms",
            "criterions": [
                {
                    "exact_snippets": "CNS(central nervous system) metastasis",
                    "criterion": "CNS metastasis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled symptoms",
                    "criterion": "CNS metastasis symptoms",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Known dysphagia or drug malabsorption",
            "criterions": [
                {
                    "exact_snippets": "Known dysphagia",
                    "criterion": "dysphagia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "drug malabsorption",
                    "criterion": "drug malabsorption",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Active infections such as acute pneumonia, hepatitis B active period",
            "criterions": [
                {
                    "exact_snippets": "Active infections such as acute pneumonia",
                    "criterion": "acute pneumonia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Active infections such as ... hepatitis B active period",
                    "criterion": "hepatitis B",
                    "requirements": [
                        {
                            "requirement_type": "active period",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* ocular surface diseases or dry eye syndrome",
            "criterions": [
                {
                    "exact_snippets": "ocular surface diseases",
                    "criterion": "ocular surface diseases",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "dry eye syndrome",
                    "criterion": "dry eye syndrome",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* skin disease with obvious symptoms and signs",
            "criterions": [
                {
                    "exact_snippets": "skin disease",
                    "criterion": "skin disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "obvious symptoms and signs",
                    "criterion": "symptoms and signs",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "obvious"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* significant cardiovascular disease, including II-IV atrioventricular block, acute myocardial infarction within 6 months, significant angina or Coronary artery bypass graft",
            "criterions": [
                {
                    "exact_snippets": "significant cardiovascular disease",
                    "criterion": "cardiovascular disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "significant"
                        }
                    ]
                },
                {
                    "exact_snippets": "II-IV atrioventricular block",
                    "criterion": "atrioventricular block",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": [
                                "II",
                                "III",
                                "IV"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "acute myocardial infarction within 6 months",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "recency",
                            "expected_value": {
                                "operator": "<=",
                                "value": 6,
                                "unit": "months"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "significant angina",
                    "criterion": "angina",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "significant"
                        }
                    ]
                },
                {
                    "exact_snippets": "Coronary artery bypass graft",
                    "criterion": "Coronary artery bypass graft",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Known existing interstitial lung disease",
            "criterions": [
                {
                    "exact_snippets": "Known existing interstitial lung disease",
                    "criterion": "interstitial lung disease",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Female patients who are pregnant or feeding, or childbearing potential patient with pregnant testing positive",
            "criterions": [
                {
                    "exact_snippets": "Female patients who are pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "feeding",
                    "criterion": "breastfeeding",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "childbearing potential patient with pregnant testing positive",
                    "criterion": "pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "positive"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Any abnormal of clinical and laboratory so that patients unsuitable to attend the trial sine in the opinion of the investigator",
            "criterions": [
                {
                    "exact_snippets": "Any abnormal of clinical and laboratory",
                    "criterion": "clinical and laboratory abnormalities",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients unable to comply with the protocol since significant psychological or psychogenic abnormal",
            "criterions": [
                {
                    "exact_snippets": "significant psychological or psychogenic abnormal",
                    "criterion": "psychological or psychogenic condition",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "significant"
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [
        {
            "line": "* APTT (activated partial thromboplastin time) and/or INR(international normalized ratio), PT≥2 ULN (the upper limit of normal)(not including patients treated by anticoagulation treatment)",
            "criterions": [
                {
                    "exact_snippets": "APTT (activated partial thromboplastin time)",
                    "criterion": "APTT",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "INR (international normalized ratio)",
                    "criterion": "INR",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "PT ≥ 2 ULN (the upper limit of normal)",
                    "criterion": "PT",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "ULN"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "not including patients treated by anticoagulation treatment",
                    "criterion": "anticoagulation treatment",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": false
                        }
                    ]
                }
            ]
        }
    ],
    "failed_miscellaneous": []
}