Precision Radiotherapy Using MR-linac for Pancreatic Neuroendocrine Tumours in MEN1 Patients

NCT ID: NCT05037461

Last Updated: 2024-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-05-01

Study Completion Date

2026-12-01

Brief Summary

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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

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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.

Conditions

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Neuroendocrine Tumor of Pancreas Multiple Endocrine Neoplasia Type 1

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Prospective cohort study
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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High-dose-high precision MR-guided radiotherapy

Radiotherapy for pancreatic NET will be delivered in an image-guided, hypofractionated scheme of 5 fractions of 8 Gy, prescribed to 95% of the planning target volume (PTV). Treatment is delivered on alternate days 2 or 3 times a week with a maximum overall treatment time of 14 days on the 1.5T MR-Linac (Elekta Unity MR-Linac).

The Gross Tumor Volume (GTV) is defines as the pNET visible on pre-treatment CT and MRI scan. No clinical target volume (CTV) is used. The PTV is made by adding a 3mm margin to the GTV.

The treatment plan is a 9-14 field intensity modulated radiotherapy (IMRT) plan with dose prescribed to 95% of the PTV. While respecting the dose constraints to adjacent tissues

Group Type EXPERIMENTAL

High-dose-high precision MR-guided radiotherapy

Intervention Type RADIATION

MR-guided radiotherapy as described in the group information

Interventions

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High-dose-high precision MR-guided radiotherapy

MR-guided radiotherapy as described in the group information

Intervention Type RADIATION

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Radboud University Medical Center

OTHER

Sponsor Role collaborator

Erasmus Medical Center

OTHER

Sponsor Role collaborator

Maastricht University Medical Center

OTHER

Sponsor Role collaborator

Leiden University Medical Center

OTHER

Sponsor Role collaborator

University Medical Center Groningen

OTHER

Sponsor Role collaborator

J.M. de Laat

OTHER

Sponsor Role lead

Responsible Party

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J.M. de Laat

Principal Investigator (Md, PhD)

Responsibility Role SPONSOR_INVESTIGATOR

Locations

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UMC Utrecht

Utrecht, , Netherlands

Site Status RECRUITING

Countries

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Netherlands

Central Contacts

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Joanne M de Laat, Md, PhD

Role: CONTACT

Phone: +31302507397

Email: [email protected]

Gerlof D Valk, MD, PhD

Role: CONTACT

Phone: +31302507397

Email: [email protected]

Facility Contacts

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Joanne M de Laat, MD, PhD

Role: primary

Gerlof D Valk, MD, PhD

Role: backup

Other Identifiers

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NL77809.041.21

Identifier Type: -

Identifier Source: org_study_id