a trial of cabozantinib in patients with advanced, low proliferative nen g3

Conditions: Neuroendocrine Tumors; Neuroendocrine Carcinoma

Summary: the main objective of this clinical trial represents the evaluation of efficacy of the tyrosine kinase inhibitor cabozantinib in patients with nen g3 with a proliferation rate of ki67 20 - 60%.


Eligibility criteria:
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 \ 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;