Clinical trial NCT03834701: Endoscopic Ultrasound-guided RadioFrequency Ablation for the Treatment Pancreatic NeuroEndocrine Neoplasms
Official title: Safety and Efficacy of Endoscopic Ultrasound-guided RadioFrequency Ablation for the Treatment of Functional and Non-functional Pancreatic NeuroEndocrine Neoplasms: A Multicenter Prospective Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Neuroendocrine Tumors
Neuroendocrine Carcinoma
Pancreas Neoplasm
Neuroendocrine Tumor Gastrointestinal, Hormone-Secreting
Lead sponsor: Catholic University of the Sacred Heart
Sponsor class: OTHER
First posted: 2019-02-08
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study evaluates the possibility and the safety of performing local therapy for Pancreatic neuroendocrine neoplasms (PanNENs) using radiofrequency ablation of the tumor under ultrasonography (EUS) guidance.

Detailed description: Pancreatic neuroendocrine neoplasms (PanNENs) are rare, but their incidence has significantly increased in the last decades. The mainstay treatment of PanNENs is surgery, which is associated with a significant benefit in term of survival but also with significant short- and long-term adverse events.

Based on the above data, less invasive alternative therapeutic interventions to avoid short- and long-term adverse events of surgery are needed.

In this context radiofrequency ablation has been reported to be effective in the treatment of these tumors in absence of major adverse events. However, the available studies on the matter are limited by small sample size and lack of standardized criteria for patient selection.

Eligibility criteria: Inclusion Criteria:

For all patients

* Age ≥18 years and \<80 years
* Signed written informed consent
* Distance from the main pancreatic duct ≥2mm
* Able to undergo endoscopic ultrasound examination
* Homogeneous enhancement at contrast harmonic EUS (CH-EUS)

For patients with functional pancreatic neuroendocrine neoplasms (F-PanNENs), almost all insulinomas

* Definitive diagnosis of a clinical syndrome related to excessive insulin secretion fasting test, insulin blood levels, C-peptide blood levels)
* Single lesion visualized at CT, and/or MRI, and/or EUS
* Size \< 20mm

For patients with non functional pancreatic neuroendocrine neoplasms (NF-PanNENs)

* EUS fine needle biopsy (FNB) proven NF-PanNENs
* 68Ga-DOTATATE PET/CT positive for a pancreatic lesion and negative for lymph nodes, liver, and other distant metastases
* Hyper- or Iso-enhancing pattern at MRI and/or CT with negative lymph nodes, liver, and other distant metastases
* G1 or G2 ≤ 5% on histological examination of EUS-guided biopsy samples utilizing EUS-FNB needles
* Diameter between 15mm and 25mm,
* Absence of symptoms
* Absence of inner calcifications

Exclusion Criteria:

* For all patients
* Known bleeding disorder that cannot be sufficiently corrected with co-fact or fresh frozen plasma (FFP)
* Use of anticoagulants that cannot be discontinued
* INR \>1.5 or platelet count \<50.000
* Previous inclusion in other studies
* Pregnancy
* Minimal distance from the main pancreatic duct \<1mm
* Inability to sign the informed consent
* Heterogeneous enhancement at contrast harmonic EUS (CH-EUS)

For patients with F-PanNENs (almost all insulinomas)

* Diagnosis work up negative excessive hormone secretion syndrome
* Multiple lesions visualized at CT, and/or MRI, and/or EUS
* Size \> 20mm
* For patients with NF-PanNENs
* G2\>5% or G3 on histological examination of EUS-guided biopsy samples
* Diameter \<15 mm and \>25 mm
* Presence of symptoms
* Presence of calcifications
* Hypo-enhancing pattern at MRI and/or CT
* 68Ga-DOTATATE PET/CT positive for lymph nodes, liver, and other distant metastasis
* Diagnosis on multiple endocrine neoplasia type 1 (MEN1) syndrome or Von Hippel Lindau syndrome
* Previous inclusion in other studies

Primary outcomes:
measure: Incidence of adverse events (AEs) after EUS-guided radiofrequency ablation (RFA)
timeFrame: 1 year
Secondary outcomes:
measure: Rates of secondary surgery
timeFrame: 1 year
Other outcomes:
Locations:
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli
state: RM
city: Rome
country: Italy
facility: Universita' del Sacro Cuore
Study officials:
affiliation: Fondazione Policlinico Universitario Agostino Gemelli
name: Alberto Larghi, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hofland J, de Herder WW, Kann PH. Turning Up the Heat: Endoscopic Ablation of Pancreatic Neuroendocrine Neoplasms. J Clin Endocrinol Metab. 2019 Nov 1;104(11):5053-5055. doi: 10.1210/jc.2019-00954. No abstract available.