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

Neuroendocrine Tumors Clinical Trial

— CABONEN  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04524208
• Other study ID #: 02679
• Status: Recruiting
• Phase: Phase 2
• Start date: March 1, 2021
• Est. completion date: October 31, 2024

Study information

• Verified date: March 2024
• Source: University Medical Center Goettingen
• Contact: Kristina Lang, Dr.
• Phone: +49 (0)511 39 60824
• Email: cabonen[@]med.uni-goettingen.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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%.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: October 31, 2024
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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;

Related Conditions & MeSH terms

• Carcinoma, Neuroendocrine
• Neuroendocrine Carcinoma
• Neuroendocrine Tumors

Intervention

Drug:
• Cabozantinib
Cabozantinib is administered orally at the dose of 60 mg per day..

Locations

Country	Name	City	State
Austria	Medizinische Universität Wien	Wien
Germany	Zentralklinik Bad Berka GmbH	Bad Berka
Germany	Universitätsklinikum Carl Gustav Carus	Dresden
Germany	Universitätsklinikum Erlangen	Erlangen
Germany	Universitätsklinikum Freiburg	Freiburg
Germany	University Medical Center Göttingen	Göttingen	Lower Saxony
Germany	Universitätsklinikum Halle	Halle
Germany	Asklepios St. Georg	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Klinikum Heidelberg	Heidelberg
Germany	Universitätsmedizin Mannheim	Mannheim
Germany	Universitätsklinikum Gießen und Marburg GmbH	Marburg
Germany	Johannes-Wesling-Klinikum Minden	Minden
Germany	Klinikum Ulm	Ulm
Germany	Universitätsklinik Würzburg	Würzburg

Sponsors (1)

Lead Sponsor	Collaborator
Karsten Gavenis

Countries where clinical trial is conducted

Austria,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety of Cabozantinib via AE and SAE assessment.	Adverse events and serious adverse events will be assessed in contingency tables.	24 months
Primary	Evaluate the efficacy of Cabozantinib treatment via DCR after 6 months.	Disease control rate (DCR) 6 months after treatment start .	6 months
Secondary	Evaluate short- and long term efficacy of Cabozantinib treatment via DCR.	DCR 3 and 12 months after treatment start.	12 months
Secondary	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
Secondary	Evaluate short- and long term efficacy of Cabozantinib treatment via PFS.	Progression free survival (PFS).	24 months
Secondary	Evaluate short- and long term efficacy of Cabozantinib treatment via OS.	Overall survival (OS).	24 months
Secondary	Evaluate exposure time.	Time on drug (TOD).	12 months
Secondary	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