Clinical trial NCT05037461: Precision Radiotherapy Using MR-linac for Pancreatic Neuroendocrine Tumours in MEN1 Patients
Official title: PRIME Study: Precision Radiotherapy Using MR-linac for Pancreatic Neuroendocrine Tumours in MEN1 Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Neuroendocrine Tumor of Pancreas
Multiple Endocrine Neoplasia Type 1
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: Radboud University Medical Center
name: Erasmus Medical Center
name: Maastricht University Medical Center
name: Leiden University Medical Center
name: University Medical Center Groningen
First posted: 2021-09-08
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective cohort study
Primary purpose: TREATMENT

Brief summary: Patients with the Multiple Endocrine Neoplasia type 1 (MEN1) syndrome are genetically predisposed for developping multiple pancreatic neuro-endocrine tumours (pNET). The management of small (pNET) in both MEN1 and sporadic cases, pose a major clinical challenge. At present, pancreatic surgery is the only curative treatment but it is associated with high morbidity. To reduce the morbidity ascosiated with surgery and thereby potentially improve quality of life for MEN1 patients introduction of less invasive techniques for treatment of pNET is important. High-dose-high precision MR-guided radiotherapy (MRgRT) holds promise as a new less invasive treatment option for pNET. The aim of this study is to assess efficiacy and safety of MRgRT for treatment of pNET in MEN1 patients.

Detailed description: Background Patients with the Multiple Endocrine Neoplasia type 1 (MEN1) syndrome are genetically predisposed for developping multiple pancreatic neuro-endocrine tumours (pNET), with a cumulative pNET incidence of over 80% at an age of 80 years. In MEN1 patients, metastatic pNET is the primary cause of premature death.

The management of small (pNET) in both MEN1 and sporadic cases, pose a major clinical challenge. At present, pancreatic surgery is the only curative treatment. Since surgery is associated with significant short- and long-term morbidity the management of small pNET depends on carefully outweighing the risk of liver metastasis leading to premature death and the morbidity of pancreatic surgery. Guidelines advocate that for tumours smaller than 2 cm an intensive watchful waiting strategy seems to be safe. However, although most pNETs remain indolent for years, many lesions eventually progress and metastasize. To prevent the development of metastases for growing tumours or tumours above 2 cm a surgical resection is advised. Due to the high incidence of pNET in the MEN1 population many MEN1 patients receive surgery for pNET in their lifespan and cope with the morbidity of pancreatic surgery. To reduce the morbidity ascosiated with surgery and thereby potentially improve quality of life for MEN1 patients introduction of less invasive techniques for treatment of pNET is important.

High-dose-high precision MR-guided radiotherapy (MRgRT) holds promise as a new less invasive treatment option for pNET. With MRgRT accurate and precise delivery of high irradiation dose levels to the pNET is possible, while monitoring the tumor with MR imaging. The UMC Utrecht has pioneered the development of this technology, and gained experience with MRgRT treatments for patients with pancreatic adenocarcinoma and other upper abdominal malignancies.

Aim Aim of this project is to assess the safety and efficacy of high-dose-high precision MRgRT for pNET in a cohort of MEN1 patients that will require surgery in the near future.

Methods Efficacy and safety of MRgRT will be explored in a prospective cohort study of MEN1 patients with pNET, the Precision Radiotherapy using MRLInac for Pancreatic Neuroendocrine Tumours in MEN1 patients (PRIME)study. The PRIME study is a single arm interventional cohort study, recruiting 20 MEN1 patients enrolled in the Dutch MEN1 Study Groups (DMSG) longitudinal cohort. Eligible patients are patients with pNET surpassing 2.0 cm, and patients with a growing pNET measuring between 1.0- 2.0 cm. Patients who give informed consent will receive MRgRT with a minimum dose to the tumour bed of 40 Gy in 5 fractions delivered within 2 weeks. The primary outcome will be the change in maximum diameter of pNET at follow-up MRI scan at 12 months after diagnosis. Secondary outcome parameters include incidence of surgical resection following MRgRT, toxicity of radiotherapy, quality of life, endocrine and exocrine pancreatic functioning, metastases free survival, overall survival and tumour characteristics on follow-up MRI.

Eligibility criteria: All patients meeting the following criteria will be assessed for in the tumour board:

* lesions measuring between 2cm and 3cm.
* pNET lesions with a size between 1.0 and 2.0 cm and moderate growth of the lesion (2-4 mm/ year) on sequential follow-up scans.
* pNET lesions with a size between 1.0 and 2.0 cm and minimal growth of the lesion (1 mm/ year) reconfirmed on 3 or more sequential follow-up scans.
* Patients with in situ remaining 1.0 - 2.0 cm lesions after previous resection of a larger lesion.

All patients with such lesion and an indication for surgery are considered eligible for participation in the PRIME study.

Exclusion Criteria:

* Suspected malignant pNET as per the tumour board assessment, including the criteria:
* pNET lesions of more than 3 cm in size
* rapid growth of pNET lesions with more than 4mm per year
* Symptomatic pNET because of hormone production, with the exception of gastrinomas which are located in the submucosa of the duodenum
* concurrent treatment with a somatostatin analog
* concurrent treatment with chemotherapy
* peptide receptor radionuclide therapy in the past 12 months
* history of radiotherapy in the upper abdominal region
* MRI contraindications as per usual clinical care, such as claustrophobia and metal or electronic implants not compatible with MRI.
* Pregnancy
* (Other) metastatic disease
* WHO performance score 3-4

Primary outcomes:
measure: Change in tumor size
timeFrame: 12 months
Secondary outcomes:
measure: Tumour progression
timeFrame: 12 months
measure: Pancreatic surgery
timeFrame: 12 months
measure: Toxicity of radiotherapy
timeFrame: 12 months
measure: Health-related quality of life by SF-36
timeFrame: 6 months, 12 months
measure: Health-related quality of life by Eq5D
timeFrame: 6 months, 12 months
measure: Health-related quality of life by PROMIS-29
timeFrame: 6 months, 12 months
measure: fasting glucose
timeFrame: 12 months
measure: blood cell count,
timeFrame: 12 months
measure: serum iron
timeFrame: 12 month in evaluation of endocrine and exocrine pancreatic function
measure: vitamin B12
timeFrame: 12 months
measure: folate
timeFrame: 12 months
measure: faecal fat test
timeFrame: 12 months
measure: faecal trypsin
timeFrame: 12 months
measure: faecal elastase
timeFrame: 12 months
measure: metastases free survival
timeFrame: 12 months
measure: overall survival
timeFrame: 12 months
Other outcomes:
Locations:
city: Utrecht
country: Netherlands
facility: UMC Utrecht
Study officials:
References: