CABONEN – a phase II trial of Cabozantinib in patients with advanced, low proliferative NEN G3

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsmedizin Goettingen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

30 Aug 2024 → 18 May 2026

Decision date (initial)

2024-09-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2024-510863-50-00

EudraCT number

2020-002541-41

ClinicalTrials.gov

NCT04524208

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy

Evaluate the efficacy of Cabozantinib treatment

Secondary objectives 4

1. Evaluate short- and long term efficacy of Cabozantinib treatment
2. Evaluate exposure time
3. Assess quality-of-life during and after Cabozantinib treatment
4. Assess general safety of Cabozantinib treatment

Conditions and MedDRA coding

Neuroendocrine Neoplasia Neuroendocrine Tumor

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 21

1. Patients with histologically confirmed diagnosis of neuroendocrine neoplasia
2. Tumor proliferation rate has to be > Ki67 20% and ≤ Ki67 60% (local assessment)
3. Male, female, or diverse patients aged ≥ 18 years without upper age limit
4. Patients with upto four different antitumoral therapies
5. At least one measurable tumor lesion in CT or MRI scan
6. Newly diagnosed or progressive disease assessed per RECIST criteria 1.1
7. Patients must have a performance status of ECOG 0-2
8. Patients must have a life expectancy of more than 3 months
9. Hb> 9 g/dl
10. Platelets >80T/µl
11. White blood cells >3T/μL
12. Total bilirubin <3mg/dl
13. AST and ALT <4xN
14. Serum creatinine <2mg/dl, eGFR >40mL/min/1.73m2
15. BUN <5xN
16. Lipase <3xN
17. Albumin ≥2.8 g/dL
18. PT/PTT ≤ 1.5 × ULN
19. Urine protein:creatinine ration ≤ 1 (Note: if proteinuria < 2g/l and increased proteinuria is ruled out by an urine teststick the protein:creatinine ratio does not need to be determined)
20. Written informed consent obtained according to international guidelines and local laws
21. Ability to understand the nature of the trial and the trial related procedures and to comply with them

Exclusion criteria 22

1. Patients with Mixed Neuroendocrine-Non-neuroendocrine Neoplasia (MINEN)
2. Patients with former treatment with TKI or VEGF receptor antagonist
3. Patients with additional malignancy <5 years in medical history (exclusion: non-invasive skin cancer)
4. Patients with symptomatic brain metastases
5. Patients with known HIV infection, acute and chronic-active hepatitis (type A, B or C) or another uncontrolled infection
6. Patients with known hypersensitivity to Cabozantinib or contraindications for treatment with Cabozantinib according to Summary of Product Characteristics (SmPC)
7. Patients with class III or IV congestive heart failure
8. Patients with prolonged QTc (for woman more than 470 ms, for men 450 ms)
9. Patients with uncontrolled hypertension (despite anti-hypertensive medication RR:>160/110 mmHg)
10. Patients with severely impaired lung function
11. Patients with history of organ transplant (exclusion: cornea transplantation)
12. Patients with clinical apparent acute or chronic gastric ulceration
13. Patients with history of hemophilia
14. Patients with surgery at the GI tract within the last 12 weeks
15. Patients with uncontrolled inflammatory bowel disease
16. Simultaneous participation in other interventional trials which could interfere with this trial; simultaneous participation in registry and diagnostic trials is allowed
17. Patient without legal capacity who is unable to understand the nature, significance and consequences of the trial
18. Previous participation in this trial
19. Concomitant use of therapeutic anticoagulation or strong CYP3A4 inducers or inhibitors (e.g. amiodarone)
20. Known or persistent abuse of medication, drugs or alcohol
21. Person who is in a relationship of dependence/employment with the sponsor or the investigator
22. Current or planned pregnancy, nursing period

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disease control rate (DCR) 6 months after treatment start (Complete Response (CR) + Partial Response (PR) + Stable Disease (SD))

Secondary endpoints 6

1. Disease control rate 3 and 12 months after treatment start
2. Objective response rate (ORR) 3 months after treatment start and best objective response rate
3. Progression free survival (PFS) and overall survival (OS)
4. Time on drug (TOD)
5. EORTC QLQ-C30 Quality of Life Questionnaire monthly for 12 months after treatment start and after 15 months
6. Serious adverse events and adverse events, Data Safety Monitoring Board (DSMB)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsmedizin Goettingen

Sponsor organisation

Universitaetsmedizin Goettingen

Address

Robert-Koch-Strasse 40, Weende Weende

City

Goettingen

Postcode

37075

Country

Germany

Scientific contact point

Organisation

Universitaetsmedizin Goettingen

Contact name

Nicole Kirchhof

Public contact point

Organisation

Universitaetsmedizin Goettingen

Contact name

Nicole Kirchhof

Locations

2 EU/EEA countries · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications