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

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

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%.

Study Overview

• Status: Active, not recruiting
• Conditions: Neuroendocrine Tumors; Neuroendocrine Carcinoma
• Intervention / Treatment: Drug: Cabozantinib

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria
    • Medizinische Universitat Wien
• Germany
  • Bad Berka, Germany, 99437
    • Zentralklinik Bad Berka GmbH
  • Dresden, Germany, 01307
    • Universitätsklinikum Carl Gustav Carus
  • Erlangen, Germany
    • Universitatsklinikum Erlangen
  • Freiburg, Germany, 79106
    • Universitatsklinikum Freiburg
  • Halle, Germany
    • Universitatsklinikum Halle
  • Hamburg, Germany
    • Asklepios St. Georg
  • Hannover, Germany
    • Medizinische Hochschule Hannover
  • Heidelberg, Germany
    • Klinikum Heidelberg
  • Mannheim, Germany
    • Universitätsmedizin Mannheim
  • Marburg, Germany, 35043
    • Universitätsklinikum Gießen und Marburg GmbH
  • Minden, Germany
    • Johannes-Wesling-Klinikum Minden
  • Ulm, Germany
    • Klinikum Ulm
  • Würzburg, Germany
    • Universitätsklinik Würzburg
  • Lower Saxony
    • Göttingen, Lower Saxony, Germany, 37075
      • University Medical Center Göttingen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment-Arm	Drug: Cabozantinib; Cabozantinib is administered orally at the dose of 60 mg per day..

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of Cabozantinib via AE and SAE assessment.	Adverse events and serious adverse events will be assessed in contingency tables.	24 months

Collaborators and Investigators

• Sponsor: Karsten Gavenis
• Investigators: Principal Investigator: Alexander König, PD Dr., University Medical Center Göttingen

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Estimated): September 30, 2024
• Study Completion (Estimated): October 31, 2024

Study Registration Dates

• First Submitted: August 18, 2020
• First Submitted That Met QC Criteria: August 21, 2020
• First Posted (Actual): August 24, 2020

Study Record Updates

• Last Update Posted (Actual): August 13, 2024
• Last Update Submitted That Met QC Criteria: August 12, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Carcinoma, Neuroendocrine; Neuroendocrine Tumors
• Other Study ID Numbers: 02679

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No