A Phase I Study of Subutinib Maleate Capsules on Toleration and Pharmacokinetics

Inclusion Criteria:

• Subjects who have histologically or cytologically confirmed solid tumors
• Subjects who have failed standard effective therapy or have a diagnosis for which no standard effective treatment is available;
• Aged 18 to 70 years old; Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2; Life expectancy greater than 3 months;
• If the subject has been given other chemotherapy drugs, it's necessary to discontinue them more than 4 weeks. If the chemotherapy drugs are Nitrosoureas and Mitomycin C, it's necessary to discontinue them more than 6 weeks. If the subject has accepted major surgery, it's necessary to wait more than 4 weeks before the subject participating in this study.
• Blood test: Hb≥100g/L(no blood transfusion within 14 days); ANC≥1.5×109/L, PLT≥100×109/L
• Biochemistry: TBIL and ALT and AST and Cr are in normal range, or creatinine clearance ≥60ml/min; Triglyceride≤3.0mmol/L; Cholesterol ≤7.75mmol/L.
• Doppler ultrasound measurement: LVEF ≥ LLN
• Female subjects should agree to take contraceptives during the study and within 6 months after the study (such as intrauterine device [IUD], contraceptive drugs or condoms); within 7 days before they enter the study, their serum or human chorionic gonadotropin should be negative, and must be in the non-lactation period; male subjects should agree to take contraceptives during the study and within 6 months after the study.
• The subject is willing to participate in this study, and he/she has signed the Informed Consent Form, with good compliance.

Exclusion Criteria:

• The subject has participated in other drug clinical research in the past 4 weeks.
• The subject is accompanied with several factors which will influence the investigational drug administration orally, such as inability to swallow or after gastrointestinal resection or chronic diarrhea or intestinal obstruction.
• Central nervous system metastasis definitely.
• The subject is suffering from hypertension or myocardial ischemia or myocardial infarction or arrhythmia (including QT interval≥440ms) or Grade I heart failure.
• If the subject's systolic BP is over 140mmhg, with diastolic BP over 90mmhg, or the subject's blood pressure is well-controlled, he/she is not permitted to enroll in this study as well.
• The subject's urinalysis displays that urinary protein ≥ ++ , combined with 24-hour urinary protein > 1.0g.
• The subject's is suffering from wounds or fractures which can not be cured for long time.
• Abnormal coagulation: The subject has bleeding tendency such as active peptic ulcer or the subject is receiving thrombolytic or anticoagulant therapy.
• There are pre-dosing arterial/venous thrombotic events on this subject, such as cerebrovascular accident (including TIA) or deep vein thrombosis or pulmonary embolism.
• The subject is accepting anticoagulants or vitamin K antagonists such as warfarin or heparin or analogue therapy; If the subject's INR ≤ 1.5, he/she is allowed to use small doses of warfarin (1mg oral q d) or small doses of aspirin(less than 100mg each day), and the purpose of the treatment should be prevention.
• Abnormal thyroid function.
• There is history of mental drug abuse occurred in the subject, or the subject is suffering from mental disorders.
• There is history of immunodeficiency occurred in the subject, including HIV positive or other acquired or congenital immunodeficiency diseases, or the subject has accepted organ transplant before.
• Lung squamous cell carcinoma.
• The subject has received small molecule targeted drug therapy of inhibition of VEGFR-2 and PDGFRβ
• According to the investigator's judgment, there are concomitant diseases which will seriously do harm to the subject's safety or obstruct the subject to complete the study.