Pancreatic Neuroendocrine Tumour - Optimal Surgical Debulking or Not

Official title

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

Overview

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

• 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.

Primary outcome measures

• Overall survival [Time frame: Five years or until death.]

Secondary outcome measures (6)

• Health economics [Time frame: Until end of trial.]
• Health-related quality of life [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: Assessed at 1 and 5 years.]
• Adverse events [Time frame: From randomisation until the end of the study period.]

Eligibility criteria

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Sweden · 4 centers

• Sahlgrenska University Hospital — Gothenburg
• Skåne University Hospital — Lund
• Karolinska University Hospital — Stockholm
• Uppsala University Hospital — Uppsala

Identifiers

NCT: NCT07273409 · PANTODON/2025

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗