Clinical trial NCT04524208: A Trial of Cabozantinib in Patients With Advanced, Low Proliferative NEN G3
Official title: CABONEN - A Phase II Trial of Cabozantinib in Patients With Advanced, Low Proliferative NEN G3
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Neuroendocrine Tumors
Neuroendocrine Carcinoma
Lead sponsor: University Medical Center Goettingen
Sponsor class: OTHER
First posted: 2020-08-24
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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 \<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;

Primary outcomes:
measure: Evaluate the efficacy of Cabozantinib treatment via DCR after 6 months.
timeFrame: 6 months
Secondary outcomes:
measure: Evaluate short- and long term efficacy of Cabozantinib treatment via DCR.
timeFrame: 12 months
measure: Evaluate short- and long term efficacy of Cabozantinib treatment via ORR.
timeFrame: 12 months
measure: Evaluate short- and long term efficacy of Cabozantinib treatment via PFS.
timeFrame: 24 months
measure: Evaluate short- and long term efficacy of Cabozantinib treatment via OS.
timeFrame: 24 months
measure: Evaluate exposure time.
timeFrame: 12 months
measure: Assess quality-of-life during and after Cabozantinib treatment.
timeFrame: 15 months
Other outcomes:
measure: Safety of Cabozantinib via AE and SAE assessment.
timeFrame: 24 months
Locations:
city: Wien
country: Austria
facility: Medizinische Universität Wien
city: Göttingen
country: Germany
facility: University Medical Center Göttingen
state: Lower Saxony
city: Bad Berka
country: Germany
facility: Zentralklinik Bad Berka GmbH
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
city: Halle
country: Germany
facility: Universitätsklinikum Halle
city: Hamburg
country: Germany
facility: Asklepios St. Georg
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Klinikum Heidelberg
city: Mannheim
country: Germany
facility: Universitätsmedizin Mannheim
city: Marburg
country: Germany
facility: Universitätsklinikum Gießen und Marburg GmbH
city: Minden
country: Germany
facility: Johannes-Wesling-Klinikum Minden
city: Ulm
country: Germany
facility: Klinikum Ulm
city: Würzburg
country: Germany
facility: Universitätsklinik Würzburg
Study officials:
affiliation: University Medical Center Göttingen
name: Alexander König, PD Dr.
role: PRINCIPAL_INVESTIGATOR
References: