A Study of Famitinib in Patients With Advanced or Metastatic Gastroenteropancreatic Neuroendocrine Tumor

Inclusion Criteria:

* Unresectable advanced or metastatic, histologically-confirmed, gastroenteropancreatic neuroendocrine tumor. Tumors must be considered well-differentiated grade G1 or grade G2 in accordance with WHO 2010 classification.
* 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).
* First-line therapy or second-line treatment (second-line treatment i.e. chemotherapy or cytokine therapy as first-line treatment failure or resistant patients).
* No previously received targeted therapy of gastroenteropancreatic neuroendocrine tumor (such as everolimus, sunitinib, or other tyrosine kinase or VEGF inhibitor treatment).
* Age between 18 and 75 years.
* ECOG Performance status ≤ 1.
* Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

* Patients with small-cell carcinoma, pheochromocytoma, paraganglioma or Merkel cell carcinoma
* Past or suffering from other cancer, but other than cure basal cell carcinoma and cervical carcinoma in situ
* Participated in other clinical trials within four weeks
* Concurrent therapy with somatostatin analogs(such as octreotide, lanreotide,etc.)
* A variety of factors that affect the oral medication (such as inability to swallow, gastrointestinal resection, chronic diarrhea and intestinal obstruction)
* Known brain metastases, spinal cord compression, cancer, meningitis, or screening CT or MRI examination revealed brain or leptomeningeal disease
* Subjects received surgery, chemotherapy, radiation therapy, cytokines treatment caused the damage has not been restored, the time interval ≤ 4 weeks, and the wound has not completely healed
* Participants have inadequate organ and marrow function as defined below:

  * hemoglobin \< 90g/L
  * platelets \< 100×10\^9/L
  * neutrophils \< 1.5×10\^9/L
  * total bilirubin ≥ 1.25×ULN
  * serum transaminase(ALT and AST ) ≥ 1.5×ULN (If liver metastases are present, serum transaminase≥ 2.5×ULN)
  * creatinine clearance rate ≤ 60ml/min
  * cholesterol ≥ 1.5×ULN and triglyceride≥ 2.5 x ULN,
  * LVEF: \< 50% by Color Doppler Ultrasonography
* Patients with uncontrollable hypertension after using single agent therapy (systolic blood pressure\> 140 mmHg, diastolic blood pressure\> 90 mmHg). Patients with more than Class I, myocardial ischemia or myocardial infarction, arrhythmia (including QT interval ≥ 450ms for male and 470ms for female) and class I heart failure.
* Urine protein ≥ + + and confirmed the 24-hour urinary protein\>1.0 g
* Long-term untreated wounds or fractures
* Coagulopathy with bleeding tendency (such as active peptic ulcer)
* Previous artery / venous thromboembolic events, such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis and pulmonary embolism
* Application of anticoagulants or vitamin K antagonists such as warfarin, heparin or its analogues; If the prothrombin time international normalized ratio (INR) ≤ 1.5, with the purpose of prevention, the use of small doses of warfarin (1mg orally, once daily) or low-dose aspirin (less than 100mg daily) is allowed
* Female: 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 article. Child bearing potential, a negative urine or serum pregnancy test result before initiating Famitinib. Male: 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 article.
* Preexisting thyroid dysfunction, even using medical therapy, thyroid function cannot maintain in the normal range
* Abuse of psychiatric drugs or dysphrenia
* Immunodeficiency: HIV positive, or other acquired immunodeficiency, congenital immunodeficiency, or organ transplantation
* 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.