Inclusion Criteria:
- Unresectable advanced or metastatic, histologically-confirmed, gastrointestinal stromal tumor.Patients has been failed from last imatinib treatment due to disease progression or unacceptable toxicity and unable to use sunitinib.
- At least 2 weeks since the last imatinib administration
- Must have at least one measurable disease by RECIST1.1 criteria(tumour lesions ≥10mm in longest diameter, malignant lymph nodes ≥15mm in short axis, scanning layer ≤ 5 mm).
- ECOG Performance status 0-1
- Participants have adequate organ and marrow function as defined below:
neutrophils ≥ 1.5×10^9/L, platelets≥ 80×10^9/L, hemoglobin≥ 90g/L （no blood transfusion within 14 days), serum transaminase(ALT and AST ) ≤ 2.5×ULN (If liver metastases are present, serum transaminase≤5×ULN), total bilirubin ≤ 1.25×ULN, cholesterol ≤ 7.75mmol/L and triglyceride≤1 x ULN, creatinine ≤1x ULN,creatinine clearance rate > 50ml/min Urine protein ≥ + + and confirmed the 24-hour urinary protein>1.0 g normal serum calcium, potassium,magnesium, phosphorus INR≤1.5 and APTT≤1.5 ULN LVEF: ≥ 50%
- Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
- Prior therapy with tyrosine kinase -inhibitor agent targeting at VEGFR, PDGFR and c-Kit
- The toxicity from previous imatinib or other treatment has not been recovered ≤ grade 1 according to CTCAE 3.0
- Have surgery or radiotherapy within 4 weeks or have temporary radiotherapy for palliative treatment within 2 weeks
- A variety of factors that affect the oral medication (such as inability to swallow, gastrointestinal resection, chronic diarrhea and intestinal obstruction)
- Other cancer diagnosed within past 5 years or currently suffering , but other than cure basal cell carcinoma and cervical carcinoma in situ
- Within 12 months before the first treatment occurs artery / venous thromboembolic events, such as cerebral vascular accident (including transient ischemic attack), deep vein thrombosis and pulmonary embolism, etc
- Uncontrollable thyroid dysfunction, even using medical therapy
- Preexisting arrhythmia (including QT interval ≥ 450ms for male and 470ms for female) and ≥ grade I heart failure
- Patients with uncontrollable hypertension after using single agent therapy (systolic blood pressure> 140 mmHg, diastolic blood pressure> 90 mmHg).
- Known acute or chronic active hepatitis
- Immunodeficiency: HIV positive, or other acquired immunodeficiency, congenital immunodeficiency, or organ transplantation
- Less than 4 weeks from the last clinical trial
- Child bearing or pregnancy female. Potential child bearing female must have a negative urine or serum pregnancy test result before initiating.
- All subjects who are not surgically sterile or postmenopausal must agree and commit to the use of a reliable method of birth control for the duration of the study and for 6 months after the last dose of test drug.
- Evidence of significant medical illness that in the investigator's judgment will substantially increase the risk associated with the subject's participation in and completion of the study.
- Mental disorders history, or Psychotropic drug abuse history
- Abuse of Psychiatric drugs or dysphrenia
- Other reasons from investigators' judgement