a study of anlotinib in patients with gastroenteropancreatic neuroendocrine tumor g3

Conditions: Gastroenteropancreatic Neuroendocrine Tumor G3

Summary: to assess the primary effects and safety of anlotinib in patients with gastroenteropancreatic neuroendocrine tumor g3.


Eligibility criteria:
inclusion criteria: * patients should participate in the study voluntarily and sign informed consent; * 18-75 years old; * histopathological proven diagnosis of high grade (g3) advanced gastroenteropancreatic neuroendocrine tumor(unresectable locally advanced or distant metastatic). the classification is based on the ki-67 proliferative index \>20%(who 2010),and provision of qualified pathological tissue for central review; * progression during or after treatment with first-line systematic chemotherapy; * at least one measurable nidus (by recist1.1); * main organs function is normal; * eastern cooperative oncology group(ecog) performance status(ps):0-1,life expectancy of more than 12 weeks; * women of childbearing potential should agree to use and utilize an adequate method of contraception (such as intrauterine device，contraceptive and condom) throughout treatment and for at least 6 months after study is stopped；the result of serum or urine pregnancy test should be negative within 7 days prior to study enrollment，and the patients required to be non-lactating；man participants should agree to use and utilize an adequate method of contraception throughout treatment and for at least 6 months after study is stopped; exclusion criteria: * diagnosed with low or intermediate (g1,g2) neuroendocrine tumors, manec, adenocarcinoma; * functional neuroendocrine tumors(nets) which need to be treated with long acting somatostatin analogue(ssas) to control disease related syndromes, such as insulinoma, gastrinoma, glucagonoma, somatostatinoma, accompanied by carcinoid syndrome, zollinger-ellison syndrome or other active symptoms; * other malignancies diagnosed within the previous 5 years, except basal cell carcinoma or cervical carcinoma in situ after radical resection； * have received anti-vascular endothelial growth factor（vegf）/vegfr targeted drugs and progressed upon these drugs； * patients with factors that could affect oral medication (such as dysphagia，chronic diarrhea, intestinal obstruction etc.) * patients with any severe and/or unable to control diseases，including： 1. blood pressure unable to be controlled ideally(systolic pressure≥150 mmhg，diastolic pressure≥100 mmhg); 2. patients with grade 1 or higher myocardial ischemia, myocardial infarction or malignant arrhythmias(including qt≥480ms) and patients with grade 1 or higher congestive heart failure (nyha classification); 3. patients with active or unable to control serious infections; 4. patients with cirrhosis, decompensated liver disease, or active hepatitis; 5. patients with poorly controlled diabetes (fasting blood glucose(fbg)\>10mmol/l) 6. urine protein ≥ ++，and 24-hour urinary protein excretion\>1.0g confirmed; * patients had surgery (except biopsy) within 28 days or the surgical incision has not fully healed before the first study drug implementation; * patients with brain metastasis or spinal cord compression which had not surgical and / or radiation therapy,or which had previous treatment but there is no clinical imaging evidence proving the condition is stable; * anti-tumor therapy was performed within 4 weeks prior to initiation of the study treatment, including but not limited to chemotherapy, radical radiotherapy, bio-targeted therapy, immunotherapy, anti-tumor treatment of traditional chinese medicine, hepatic artery embolization, hepatic metastatic cryoablation or radiofrequency ablation surgery.palliative radiotherapy for a bone metastasis lesion within 2 weeks prior to the initiation of the investigational treatment; * the toxic reaction of previous anticancer treatment has not been restored to grade 0 or 1 (except hair loss); * patients with arterial or venous thromboembolic events occurred within 6 months, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis and pulmonary embolism; * imaging showed tumors have involved important blood vessels or by investigators determine likely during the follow-up study and cause fatal hemorrhage; * patients with drug abuse history and unable to get rid of or patients with mental disorders; * patients participated in other anticancer drug clinical trials within 4 weeks; * history of immunodeficiency; * pregnancy(positive detection of pregnancy before drug use)or lactation; * patients with concomitant diseases which could seriously endanger their own safety or could affect completion of the study according to investigators' judgment;