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b'Signed Informed Consent Form.' |
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b'Men or women aged more than or equal to (\\u2265) 18 years, and less than (<) 75 years.' |
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b'Histologically or cytologically confirmed solid tumor, either refractory to standard' |
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b'therapy or for which no effective standard therapy is available.' |
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b'ECOG performance status of 0-1, estimated life expectancy greater than (>) three' |
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b'months.' |
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b'At least 1 lesion that has not previously been irradiated, that has not been chosen' |
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b'for biopsy during the study screening period, and that can be accurately measured at' |
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b'Baseline as \\u2265 10 mm in the longest diameter (except lymph nodes, which must have short' |
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b'axis \\u2265 15mm) with computerized tomography (CT) or magnetic resonance imaging (MRI),' |
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b'whichever is suitable for accurately repeated measurements.' |
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b'Females should be using adequate contraceptive measures throughout the study; should' |
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b'not be breastfeeding at the time of screening, during the study and until 3 months' |
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b'after completion of the study; and must have a negative pregnancy test prior to start' |
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b'of dosing if of childbearing potential or must have evidence of non-childbearing' |
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b'potential by fulfilling 1 of the following criteria at Screening:' |
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b'Postmenopausal defined as age more than 50 years and amenorrheic for at least 12' |
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b'months following cessation of all exogenous hormonal treatments.' |
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b'Women under 50 years old would be considered postmenopausal if they have been' |
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b'amenorrheic for 12 months or more, following cessation of exogenous hormonal' |
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b'treatments, and with luteinizing hormone (LH) and follicle-stimulating hormone' |
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b'(FSH) levels in the postmenopausal range for the laboratory.' |
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b'Documentation of irreversible surgical sterilization by hysterectomy, bilateral' |
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b'oophorectomy, or bilateral salpingectomy, but not by tubal ligation.' |
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b'Male patients should be willing to use barrier contraception (i.e., condoms).' |
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b'Treatment with any of the following:'
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b'Any cytotoxic chemotherapy, investigational agents, or anticancer drugs for the'
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b'treatment of advanced solid tumor used for a previous treatment regimen or'
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b'clinical study within 14 days of the first dose of study drug.'
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b'Drugs with immunoregulatory indications within 7 days of the first dose of study'
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b'drug.'
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b'Medications that are predominantly CYP3A4 strong inhibitors or inducers or'
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b'ensitive substrates of CYP3A4 with a narrow therapeutic range within 7 days of'
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b'the first dose of study drug.'
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b'Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) ,'
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b'unrecovered wound, ulcer, or fracture within 4 weeks of the first dose of study'
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b'drug.'
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b'Radiotherapy with a limited field of radiation for palliation within 1 week of'
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b'the first dose of study drug, with the exception of patients receiving radiation'
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b'to > 30% of the bone marrow or with a wide field of radiation within 4 weeks of'
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b'the first dose of study drug.'
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b'Previous or current treatment with drugs targeting the c-MET/HGF pathway.'
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b'Any unresolved toxicities from prior therapy greater than Common Terminology Criteria'
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b'for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment, with the'
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b'exception of alopecia.'
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b'Spinal cord compression or brain metastases unless asymptomatic, stable, and not'
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b'requiring steroids for at least 2 weeks prior to start of study treatment. Meningeal'
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b'or brainstem metastases.'
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b'Pleural or peritoneal effusion requiring clinical intervention (except for effusion'
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b'table at least 1 week after clinical intervention). Pericardial effusion (except for'
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b'non-tumorous micro pericardial effusions).'
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b'The tumor compresses or invades important surrounding organs (such as trachea,'
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b'esophagus, superior vena cava, heart, and aorta, etc), or causes significant'
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b'mediastinal displacement.'
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b'Any evidence of severe or uncontrolled systemic diseases, including uncontrolled'
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b"hypertension or active bleeding diatheses, which, in the investigator's opinion, makes"
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b'it undesirable for the patient to participate in the trial or which would jeopardize'
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b'compliance with the protocol such as active infection (e.g., hepatitis B, hepatitis C,'
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b'or human immunodeficiency virus [HIV]). Screening for chronic conditions is not'
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b'required.'
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b'Any active infection requiring treatment or systemic anti-infective agent used in one'
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b'week prior to first dose administration.'
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b'Active hemoptysis, active diverticulitis, peritoneal abscess, gastrointestinal'
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b'obstruction that requires clinical intervention.'
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b'Medical history of arterial thrombosis, embolism or ischemia, such as myocardial'
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b'infarction, unstable angina, cerebrovascular accident or transient ischemic attack,'
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b'within 6 months prior to screening. Medical history of deep vein thrombosis, pulmonary'
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b'embolism, or any other serious thromboembolism within 3 months prior to screening.'
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b'Varices of the esophagus or stomach that require immediate intervention (e.g.,'
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b'clerotherapy).'
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b'Any life-threatening bleeding events or Grade 3 or 4 gastrointestinal/varicose'
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b'bleeding events requiring blood transfusion, endoscopy, or surgical treatment occurred'
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b'within 3 months prior to enrollment.'
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b'Hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh Grade B or more severe'
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b'cirrhosis.'
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b'Any of the following cardiac criteria:'
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b'Resting corrected QT interval (QTc) > 470 ms obtained from electrocardiogram'
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b"(ECG), using the screening clinic's ECG machine and Fridericia's formula for QT"
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b'interval correction (QTcF).'
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b'Any clinically important abnormalities in rhythm, conduction, or morphology of'
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b'the resting ECG (e.g., complete left bundle branch block, third-degree heart'
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b'block, second-degree heart block, PR interval > 250 ms).'
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b'Any factors that increase the risk of QTc prolongation or risk of arrhythmic'
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b'events, such as heart failure, hypokalemia, congenital long QT syndrome, family'
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b'history of long QT syndrome, or unexplained sudden death under 40 years of age in'
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b'first degree relatives or any concomitant medication known to prolong the QT'
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b'interval.'
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b'Left ventricular ejection fraction (LVEF) \\u2264 40%.'
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b'Any newly diagnosed clinically important arrhythmia which is no reasonable reason'
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b'other than tumor to explain within 3 months prior to enrollment.'
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b'Past medical history of interstitial lung disease, drug-induced interstitial lung'
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b'disease, radiation pneumonitis that required steroid treatment, or any evidence of'
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b'clinically active interstitial lung disease.'
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b'Inadequate bone marrow reserve or organ function, as demonstrated by any of the'
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b'following laboratory values:'
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b'Absolute neutrophil count (ANC) <1.5\\xd7109 / L'
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b'Platelet count <100\\xd7109 / L'
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b'Hemoglobin <90 g/L\\uff08<9 g/dL\\uff09'
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b'Alanine aminotransferase (ALT) > 2.5 \\xd7 upper limit of normal (ULN) if no'
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b'demonstrable liver metastases or > 5 \\xd7 ULN in the presence of liver metastases.'
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b'Aspartate aminotransferase (AST) > 2.5 \\xd7 ULN if no demonstrable liver metastases'
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b'or > 5 \\xd7 ULN in the presence of liver metastases.'
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b'Total bilirubin (TBL) > 1.5 \\xd7 ULN if no liver metastases or > 3 \\xd7 ULN in the'
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b"presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or"
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b'liver metastases.'
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b'Serum albumin (ALB) < 28 g/L, patients corrected by supplementation with human'
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b'albumin should to exclude.'
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b'Creatinine > 1.5 \\xd7 ULN concurrent with creatinine clearance < 50 mL/min (measured'
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b'or calculated by the Cockcroft-Gault equation); confirmation of creatinine'
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b'clearance is only required when creatinine is > 1.5 \\xd7 ULN.'
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b'Urine protein \\u2265 2+. When the Urine protein \\u2265 2+ at baseline, 24-hour urine for'
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b'collection, if the protein content in urine is less than 1g for 24 hours,'
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b'Refractory nausea, vomiting, or chronic gastrointestinal diseases, inability to'
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b'wallow the study drug, or previous significant bowel resection that would preclude'
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b'adequate absorption of HS-10241.'
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b'History of hypersensitivity to any active or inactive ingredient of HS-10241 or to'
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b'drugs with a similar chemical structure or class to HS-10241.'
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b'Judgment by the investigator that the patient should not participate in the study if'
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b'the patient is unlikely to comply with study procedures, restrictions, and'
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b'requirements.'
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b'Any disease or condition that, in the opinion of the investigator, would compromise'
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b'the safety of the patient or interfere with study assessments.'
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b'History of other primary malignancies, excluding:'
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b'Malignancies that have been recovered, have been inactive for \\u22655 years prior to'
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b'Non-melanoma skin cancer or malignant freckle mole with adequate treatment and no'
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b'evidence of disease recurrence.'
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b'Carcinoma in situ with adequate treatment and no evidence of disease recurrence.'
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b'Women who are breastfeeding or have a positive serum pregnancy test at Screening.'
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b'Any uncontrolled metabolic dysfunction, local or systemic disease that is not caused'
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b'by a malignant tumor, disease or symptoms secondary to the tumor, can lead to higher'
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b'medical risk and/or uncertainty in the evaluation of survival.'
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