Pancreatic Neuroendocrine Tumor
Conditions
Keywords
Pan-NET, Stage 4, Debulking surgery, Non-functional Pan-NET, GI-WHO grade 1-2 Pan-NET
Brief summary
Pancreatic neuroendocrine tumours (pan-NETs) are neoplasms arising from the endocrine cells of the pancreas. Although pan-NET are quite rare, the incidence is on the rise and together with other abdominal neuroendocrine tumours an approximate incidence in Sweden would be 850 patients per year extrapolating from Norwegian data. Pan-NET are divided into symptomatic hormone producing tumours (such as insulinomas/glucagonomas/VIPomas) or non-functioning tumours that often are asymptomatic. As early symptoms often are lacking in non-functioning-pan-NET, many patients present with distant metastases and are thus beyond a curative surgical approach at the time of diagnosis. Metastatic non-functioning pan-NETs present a significant challenge and the optimal management remains a subject of debate. This is a prospective, two armed, parallel, randomised, controlled, international multi-centre study, aiming to investigate if a near-total tumour debulking (intervention) in metastatic (stage 4) GI-WHO grade 1-2 pan- NET, with or without oncologic treatment, is superior to oncologic treatment alone (control), with regards to overall survival, health-related quality of life, participant performance status, time until hospitalisation, adverse event characteristics and cost in the short and long term.
Interventions
PROCEDUREDebulking surgery
All subjects are divided into STRATUM 1 and STRATUM 2 prior to randomisation. For subjects in STRATUM 1, the surgical resection, alone or in combination with ablative procedures, aim to achieve at least 70% debulking of the total tumour volume, with acceptable risk and acceptable functional liver remnant (FLR). For subjects in STRATUM 2 the aim is to resect or ablate all FluDeoxyGlucose-Positron emission tomography (FDG-PET) avid disease with acceptable risk and acceptable FLR.
Sponsors
Uppsala University
Uppsala Clinical Research Center, Sweden
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Prospective, two armed, parallel, randomised, controlled, international multi-centre study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pan- NET, ENETS/AJCC stage 4 determined by CT or PET/CT * Primary tumour or metastases confirmed as Pancreatic NET GI-WHO grade 1-2 pan-NET by histology or cytology * Age ≥ 18 years * Written informed consent obtained
Exclusion criteria
* Subject not fit for surgery due to comorbidity or advanced age (reason to be specified) * Risk of surgery deemed too high by MDT or Surgeon (reason to be specified) * Previous surgery for pan-NET. * Hormonal symptoms caused by a functional pan-NET, not controllable by medical therapy, indicating debulking surgery. * Previously included in the current study. * Pregnancy * The study subject does not fit into either STRATA: a) STRATUM 1: Less than 70% of the total tumour volume can be debulked, b) STRATUM 2: no FDG-PET avid disease is observed OR all (100%) FDG-PET avid tumour is not resectable. * Other reason in the opinion of the Principal Investigator (reason to be specified).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | Five years or until death. | Time from randomisation to death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Health economics | Until end of trial. | Estimation of total health economic costs for hospitalisation, ICU stay, and treatments given for the pan-NET disease in each group during follow-up. |
| Health-related quality of life | The questionnaire will be filled in by the study subject before randomisation, at 3 months (+/2weeks), 6 months, and at 1, 2, 3, 4 and 5 years (+/4weeks) after randomisation. | Data on health-related quality of life will be gathered with the EORTC Core Quality of Life questionnaire (EORTC QLQ-C30). The questionnaire is designed to measure cancer subjects' physical, psychological and social functions. It is composed of multi-item scales and single items. |
| Performance status | Assessed at screening, at 3 months (+/2weeks), 6 months, and at 1, 2, 3, 4 and 5 years (+/4weeks) after randomisation. | Performance status is measured using the Karnofsky performance status scale The scale ranges from 100 to 0, with higher scores indicating better functional status. |
| Days out of hospital | Assessed at 3 months (+/2weeks), 6 months, and at 1, 2, 3, 4 and 5 years (+/4weeks) after randomisation. | Total number of days alive outside hospital. |
| Days out of intensive care unit | Assessed at 1 and 5 years. | Total number of days alive outside intensive care unit. |
| Adverse events | From randomisation until the end of the study period. | Severe, life threatening and fatal adverse events possibly or probably related to pan-NET treatment during follow-up. |
Countries
Sweden
Contacts
CONTACTOlov Norlén, Professor and Consultant, MD, PhD
CONTACTCarina Alvfors, Project Manager
PRINCIPAL_INVESTIGATOROlov Norlén, MD, PhD
Uppsala University Hospital
Outcome results
None listed