A Trial of Cabozantinib in Patients With Advanced, Low Proliferative NEN G3

Inclusion Criteria: 1. Patient with histologically confirmed diagnosis of neuroendocrine neoplasia; 2. Tumor proliferation rate has to be between Ki67 20% to 60% (local assessment); 3. Male, female, or diverse patients aged \> 18 years without upper age limit; 4. At least one measurable tumor lesions in CT or MRI scan; 5. Newly diagnosed or progressive disease assessed per RECIST criteria 1.1; 6. Patients must have a performance status of ECOG 0-2; 7. Patients must have a life expectancy of more than 3 months; 8. Hb\> 9 mg/dl; 9. platelets \>80T/µl; 10. white blood cells \>3T/μL; 11. total bilirubin \<3mg/dl; 12. AST and ALT \<4xN; 13. Serum creatinine \<2mg/dl, eGFR \>40mL/min/1.73m2; 14. BUN \<5xN; 15. lipase \<3xN; 16. albumin ≥2.8 g/dL; 17. PT/PTT ≤ 1.5 × ULN; 18. urine protein: creatinine ratio ≤ 1; 19. Written informed consent obtained according to international guidelines and local laws; 20. Ability to understand the nature of the trial and the trial related procedures and to comply with them; Exclusion Criteria: 1. Patients younger than 18 years; 2. Patients with Mixed Neuroendocrine-Non-neuroendocrine Neoplasia (MINEN); 3. Patients with former treatment with TKI or VEGF receptor antagonist; 4. Patients with additional malignancy \<5 years in medical history (exclusion: non-invasive skin cancer); 5. Patients with symptomatic brain metastases; 6. Patients with Known HIV infection, infectious hepatitis (type A, B or C) or another uncontrolled infection; 7. Patients with Known hypersensitivity to Cabozantinib or contraindications for treatment with Cabozantinib according to Summary of Product Characteristics (SmPC); 8. Patients with class III or IV congestive heart failure; 9. Patients with QTc more than 500 ms or 140% of normal range according to age; 10. Patients with uncontrolled hypertension; 11. Patients with severely impaired lung function; 12. Patients with history of organ transplant (exclusion: cornea transplantation); 13. Patients with clinical apparent acute or chronic gastric ulceration; 14. Patients with history of hemophilia; 15. Patients with surgery at the GI tract within the last 12 weeks; 16. Patients with patients with uncontrolled inflammatory bowel disease; 17. Simultaneous participation in other interventional trials which could interfere with this trial; simultaneous participation in registry and diagnostic trials is allowed 18. Patient without legal capacity who is unable to understand the nature, significance and consequences of the trial; 19. Previous participation in this trial 20. concomitant use of therapeutic anticoagulation or strong CYP3A4 inducers or inhibitors (e.g. amiodarone); 21. Known or persistent abuse of medication, drugs or alcohol; 22. Person who is in a relationship of dependence/employment with the sponsor or the investigator; 23. Patients who cannot give informed consent; 24. Current or planned pregnancy, nursing period;