A phase II trial of Cabozantinib medication in patients with advanced, high-grade neuroendocrine neoplasms, which are either well-differentiated neuroendocrine tumors or poor-differentiated neuroendocrine carcinoma but with a low proliferation rate. Both neuroendocrine neoplasms are insensitive against the available chemotherapy choice, making the newly investigated medication a new hope for better management of these subtypes.
- Conditions
- We will include patients with NET G3 and upto four prior antitumoral treatment lines and NEC Ki67 low after failure of standard treatment with conventional chemotherapy.Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-002541-41-DE
- Lead Sponsor
- niversitätsmedizin Göttingen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 0
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 up to 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 28
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 17
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 women 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 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Evaluate the efficacy of Cabozantinib treatment;Secondary Objective: Evaluate short- and long term efficacy of Cabozantinib treatment, evaluate necessary exposure time, assess quality-of-life during and after Cabozantinib treatment, and to assess general safety of Cabozantinib treatment <br>;Primary end point(s): Disease control rate (DCR) (Complete Response, CR + Partial Response, PR + Stable Disease, SD);Timepoint(s) of evaluation of this end point: 6 months after treatment start
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Disease control rate (DCR).<br>Progression free survival (PFS) and overall survival (OS).<br>Time on drug (TOD).<br>EORTC QLQ-C30 Quality of Life Questionnaire monthly.<br>Serious adverse events and adverse events, Data Safety Monitoring Board (DSMB) after 20 patients.;Timepoint(s) of evaluation of this end point: 3 and 12 months after treatment start.<br>For the QoL: monthly for 12 months after treatment start and after 15 months