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

Phase 2

Active, not recruiting

• Conditions: Neuroendocrine Tumors; Neuroendocrine Carcinoma
• Interventions: Drug: Cabozantinib

• Registration Number: NCT04524208
• Lead Sponsor: Karsten Gavenis

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%.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-08-18
• Study First Submitted QC: 2020-08-21
• Study First Posted: 2020-08-24
• Study Start: 2021-03-01
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-12
• Last Update Posted: 2024-08-13
• Primary Completion: 2024-09-30
• Study Completion: 2024-10-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 45

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;

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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;

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment-Arm	Cabozantinib	-

Primary Outcome Measures

Name	Time	Method
Evaluate the efficacy of Cabozantinib treatment via DCR after 6 months.	6 months	Disease control rate (DCR) 6 months after treatment start .

Secondary Outcome Measures

Name	Time	Method
Evaluate short- and long term efficacy of Cabozantinib treatment via DCR.	12 months	DCR 3 and 12 months after treatment start.
Evaluate short- and long term efficacy of Cabozantinib treatment via ORR.	12 months	Objective response rate (ORR) 3, 6 and 12 months after treatment start and best objective response rate.
Evaluate exposure time.	12 months	Time on drug (TOD).
Assess quality-of-life during and after Cabozantinib treatment.	15 months	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.
Evaluate short- and long term efficacy of Cabozantinib treatment via PFS.	24 months	Progression free survival (PFS).
Evaluate short- and long term efficacy of Cabozantinib treatment via OS.	24 months	Overall survival (OS).

Trial Locations

Locations (15)

Medizinische Universität Wien; 🇦🇹 Wien, Austria

University Medical Center Göttingen; 🇩🇪 Göttingen, Lower Saxony, Germany

Universitätsklinikum Carl Gustav Carus; 🇩🇪 Dresden, Germany

Universitätsklinikum Erlangen; 🇩🇪 Erlangen, Germany

Universitätsklinikum Freiburg; 🇩🇪 Freiburg, Germany

Universitätsklinikum Halle; 🇩🇪 Halle, 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, Germany

Asklepios St. Georg; 🇩🇪 Hamburg, Germany

Zentralklinik Bad Berka GmbH; 🇩🇪 Bad Berka, Germany