Pancreatic Neuroendocrine Tumour - Optimal Surgical Debulking or Not (PANTODON)

PANcreatic Neuroendocrine Tumour - Optimal Surgical Debulking Or Not (PANTODON). A Prospective, Two Armed, Parallel, Randomised, Controlled International Multicentre Study on WHO Grade 1-2, Stage 4 Pancreatic NET

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.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Neuroendocrine Tumor
• Intervention / Treatment: Procedure: Debulking surgery

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Olov Norlén, Professor and Consultant, MD, PhD; Phone Number: +46 18 611 00 00; Email: olov.norlen@uu.se
• Study Contact Backup: Name: Carina Alvfors, Project Manager; Phone Number: +46 18 611 00 00; Email: Carina.Alvfors@ucr.uu.se

Study Locations

• Sweden
  • Gothenburg, Sweden
    • Recruiting
    • Sahlgrenska University Hospital
    • Contact: Anders Thornell, MD, PhD; Phone Number: +46 31 342 10 00; Email: anders.thornell@vgregion.se
  • Lund, Sweden
    • Not yet recruiting
    • Skane University Hospital
    • Contact: Erik Nordenström, MD, PhD; Phone Number: +46 46 17 23 05; Email: erik.nordenstrom@med.lu.se
  • Stockholm, Sweden
    • Recruiting
    • Karolinska University Hospital
    • Contact: Carolina Nylen, MD, PhD; Phone Number: +46 8- 23 700 00; Email: carolina.nylen@ki.se
  • Uppsala, Sweden
    • Recruiting
    • Uppsala University Hospital
    • Contact: Olov Norlén, MD, PhD; Phone Number: +46 18 611 00 00; Email: olov.norlen@uu.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Surgical group; Debulking surgery followed by oncologic treatment according to standard routine. Further debulking surgery or ablation may be continued during follow-up to reduce tumour load.	Procedure: Debulking 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.
No Intervention: Non-surgical group; Oncologic treatment alone. No surgical or thermal ablative treatments will be planned after randomisation. Any surgical or ablative procedure for pan-NET that is performed after randomisation in the Non-surgical group is considered as a protocol deviation. However, such procedures may be carried out if clinically indicated and no other equivalent or better oncological options for treatment are available. The surgery is then documented as oncological treatment in eCRF and the subject will continue follow-up in the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Time from randomisation to death.	Five years or until death.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health economics	Estimation of total health economic costs for hospitalisation, ICU stay, and treatments given for the pan-NET disease in each group during follow-up.	Until end of trial.
Health-related quality of life	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.	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.
Performance status	Performance status is measured using the Karnofsky performance status scale The scale ranges from 100 to 0, with higher scores indicating better functional status.	Assessed at screening, at 3 months (+/2weeks), 6 months, and at 1, 2, 3, 4 and 5 years (+/4weeks) after randomisation.
Days out of hospital	Total number of days alive outside hospital.	Assessed at 3 months (+/2weeks), 6 months, and at 1, 2, 3, 4 and 5 years (+/4weeks) after randomisation.
Days out of intensive care unit	Total number of days alive outside intensive care unit.	Assessed at 1 and 5 years.
Adverse events	Severe, life threatening and fatal adverse events possibly or probably related to pan-NET treatment during follow-up.	From randomisation until the end of the study period.

Collaborators and Investigators

• Sponsor: Uppsala University
• Collaborators: Uppsala Clinical Research Center, Sweden
• Investigators: Principal Investigator: Olov Norlén, MD, PhD, Uppsala University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2026
• Primary Completion (Estimated): May 31, 2033
• Study Completion (Estimated): May 31, 2033

Study Registration Dates

• First Submitted: September 24, 2025
• First Submitted That Met QC Criteria: November 27, 2025
• First Posted (Actual): December 9, 2025

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 21, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Stage 4; Debulking surgery; Pan-NET; Non-functional Pan-NET; GI-WHO grade 1-2 Pan-NET
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Neoplasms, Glandular and Epithelial; Adenoma; Pancreatic Neoplasms; Adenoma, Islet Cell; Surgical Procedures, Operative; Cytoreduction Surgical Procedures
• Other Study ID Numbers: PANTODON/2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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