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

Inclusion criteria

• Patient with histologically confirmed diagnosis of neuroendocrine neoplasia;
• Tumor proliferation rate has to be between Ki67 20% to 60% (local assessment);
• Male, female, or diverse patients aged > 18 years without upper age limit;
• At least one measurable tumor lesions in CT or MRI scan;
• Newly diagnosed or progressive disease assessed per RECIST criteria 1.1;
• Patients must have a performance status of ECOG 0-2;
• Patients must have a life expectancy of more than 3 months;
• Hb> 9 mg/dl;
• platelets >80T/µl;
• white blood cells >3T/μL;
• total bilirubin <3mg/dl;
• AST and ALT <4xN;
• Serum creatinine <2mg/dl, eGFR >40mL/min/1.73m2;
• BUN <5xN;
• lipase <3xN;
• albumin ≥2.8 g/dL;
• PT/PTT ≤ 1.5 × ULN;
• urine protein: creatinine ratio ≤ 1;
• Written informed consent obtained according to international guidelines and local laws;
• Ability to understand the nature of the trial and the trial related procedures and to comply with them;

Exclusion criteria

• Patients younger than 18 years;
• Patients with Mixed Neuroendocrine-Non-neuroendocrine Neoplasia (MINEN);
• Patients with former treatment with TKI or VEGF receptor antagonist;
• Patients with additional malignancy <5 years in medical history (exclusion: non-invasive skin cancer);
• Patients with symptomatic brain metastases;
• Patients with Known HIV infection, infectious hepatitis (type A, B or C) or another uncontrolled infection;
• Patients with Known hypersensitivity to Cabozantinib or contraindications for treatment with Cabozantinib according to Summary of Product Characteristics (SmPC);
• Patients with class III or IV congestive heart failure;
• Patients with QTc more than 500 ms or 140% of normal range according to age;
• Patients with uncontrolled hypertension;
• Patients with severely impaired lung function;
• Patients with history of organ transplant (exclusion: cornea transplantation);
• Patients with clinical apparent acute or chronic gastric ulceration;
• Patients with history of hemophilia;
• Patients with surgery at the GI tract within the last 12 weeks;
• Patients with patients with uncontrolled inflammatory bowel disease;
• Simultaneous participation in other interventional trials which could interfere with this trial; simultaneous participation in registry and diagnostic trials is allowed
• Patient without legal capacity who is unable to understand the nature, significance and consequences of the trial;
• Previous participation in this trial
• concomitant use of therapeutic anticoagulation or strong CYP3A4 inducers or inhibitors (e.g. amiodarone);
• Known or persistent abuse of medication, drugs or alcohol;
• Person who is in a relationship of dependence/employment with the sponsor or the investigator;
• Patients who cannot give informed consent;
• Current or planned pregnancy, nursing period;