CABONEN – a phase II trial of Cabozantinib in patients with advanced, low proliferative NEN G3

Prior treatment

• Patients with surgery at the GI tract within the last 12 weeks
• Previous participation in this trial
• Concomitant use of therapeutic anticoagulation or strong CYP3A4 inducers or inhibitors (e.g. amiodarone)
• Patients with former treatment with TKI or VEGF receptor antagonist
• Known or persistent abuse of medication, drugs or alcohol

Other illness

• Patients with history of organ transplant (exclusion: cornea transplantation)
• Patients with history of hemophilia
• Patients with uncontrolled inflammatory bowel disease
• Patients with known HIV infection, acute and chronic-active 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 uncontrolled hypertension (despite anti-hypertensive medication RR:>160/110 mmHg)

Lab values

• Patients with prolonged QTc (for woman more than 470 ms, for men 450 ms)

Age

• Patients with additional malignancy <5 years in medical history (exclusion: non-invasive skin cancer)

Other

• Patients with Mixed Neuroendocrine-Non-neuroendocrine Neoplasia (MINEN)
• Patients with severely impaired lung function
• Patients with clinical apparent acute or chronic gastric ulceration
• 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
• Person who is in a relationship of dependence/employment with the sponsor or the investigator
• Current or planned pregnancy, nursing period
• Patients with symptomatic brain metastases

• Patients with histologically confirmed diagnosis of neuroendocrine neoplasia
• 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 ration ≤ 1 (Note: if proteinuria < 2g/l and increased proteinuria is ruled out by an urine teststick the protein:creatinine ratio does not need to be determined)
• Tumor proliferation rate has to be > Ki67 20% and ≤ Ki67 60% (local assessment)
• 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
• Male, female, or diverse patients aged ≥ 18 years without upper age limit
• Patients with upto four different antitumoral therapies
• At least one measurable tumor lesion 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 g/dl