A Study of Anlotinib in Patients With Gastroenteropancreatic Neuroendocrine Tumor G3

Study Overview
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Brief Summary
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To assess the primary effects and safety of Anlotinib in patients with Gastroenteropancreatic Neuroendocrine Tumor G3.

Official Title
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A Single Group, Open Label, Multi-center Clinical Trial to Assess the Efficacy and Safety of Anlotinib in Patients With Gastroenteropancreatic Neuroendocrine Tumor G3

Conditions
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Gastroenteropancreatic Neuroendocrine Tumor G3

Intervention / Treatment
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* Drug: Anlotinib


Participation Criteria
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Eligibility Criteria
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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： Blood pressure unable to be controlled ideally(systolic pressure≥150 mmHg，diastolic pressure≥100 mmHg); 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); Patients with active or unable to control serious infections; Patients with cirrhosis, decompensated liver disease, or active hepatitis; Patients with poorly controlled diabetes (fasting blood glucose(FBG)>10mmol/L) 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;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anlotinib<br> | Drug: Anlotinib<br>* Anlotinib is followed Day 1 to day 14 by 7 days off treatment in a 21-day cycle） and it should be continued until disease progression or intolerable toxicity or patients withdrawal of consent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival(PFS) |  | From randomization，each 42 days up to progressive disease(PD) or death(up to 24 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate(ORR) |  | each 42 days up to intolerance the toxicity or PD (up to 24 months) | 
| Overall survival(OS) |  | From randomization until death (up to 24 months) | 
| Disease Control Rate(DCR) |  | each 42 days up to intolerance the toxicity or PD (up to 24 months) |