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

Study Overview
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Brief Summary
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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%.

Official Title
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CABONEN - A Phase II Trial of Cabozantinib in Patients With Advanced, Low Proliferative NEN G3

Conditions
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Neuroendocrine Tumors, Neuroendocrine Carcinoma

Intervention / Treatment
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* Drug: Cabozantinib


Participation Criteria
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Eligibility Criteria
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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;

Ages Eligible for Study
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Minimum Age: 18 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: Treatment-Arm<br> | Drug: Cabozantinib<br>* Cabozantinib is administered orally at the dose of 60 mg per day..<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the efficacy of Cabozantinib treatment via DCR after 6 months. | Disease control rate (DCR) 6 months after treatment start . | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate short- and long term efficacy of Cabozantinib treatment via DCR. | DCR 3 and 12 months after treatment start. | 12 months | 
| Evaluate short- and long term efficacy of Cabozantinib treatment via ORR. | Objective response rate (ORR) 3, 6 and 12 months after treatment start and best objective response rate. | 12 months | 
| Evaluate short- and long term efficacy of Cabozantinib treatment via PFS. | Progression free survival (PFS). | 24 months | 
| Evaluate short- and long term efficacy of Cabozantinib treatment via OS. | Overall survival (OS). | 24 months | 
| Evaluate exposure time. | Time on drug (TOD). | 12 months | 
| Assess quality-of-life during and after Cabozantinib treatment. | EORTC QLQ-C30 Quality of Life Questionnaire monthly for 12 months after treatment start and after 15 months. Different questions regarding Quality of Life on a scale of 1 - 4. The lower the numbers, the better the quality of Life. | 15 months |