Early Screening of Pancreatic Lesions : Development of New Imaging Tools

Pancreatic Cancer Clinical Trial

— PAIR-PANCREAS  

Official title:

Early Stages of Pancreatic Cancer Associated With Obesity and Metabolic Syndrome: Prevention and Screening Tools - Imaging of Fatty Pancreas in Humans: Correlation With Pathological Analysis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04007640
• Other study ID #: 2018-A02712-53
• Status: Recruiting
• Phase: N/A
• Start date: June 18, 2019
• Est. completion date: October 27, 2023

Study information

• Verified date: July 2022
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Anne COUVELARD, MD
• Phone: 140258012
• Email: anne.couvelard[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Obesity, diabetes and metabolic syndrome (MS) have all been associated with increase of pancreatic cancer (PK) risk. The precise role of obesity and diabetes and the pathways involved in the early oncogenic phases of PK associated with MS are not well known. The investigators hypothesize that it is possible to decipher this specific "fat-fibrosis-neoplastic sequence", to develop new imaging tools adapted to follow its progression, to test the benefit of treatments to slow this sequence and prevent the development of PK in obese and diabetic patients.This project is in line with a prevention strategy, by planning to understand the physiopathological pathways involved in MS leading to PK, to develop tools useful to screen early precancerous lesions in order to diagnose and treat patients at high risk, before cancer involvement.

This clinical trial is part of the INCA PAIR PANCREAS project : Early stages of pancreatic cancer associated with obesity and metabolic syndrome:

prevention and screening tools - Imaging of fatty pancreas in humans: correlation with pathological analysis, which includes 3 main coordinated objectives an in vitro approach an in vivo approach and this study (clinical approach).

Description:

Translational approach with direct application to humans, to test specific imaging MRI sequences in obese patients.

Obesity and metabolic syndrome are a well-known risk factor of pancreatic cancer. Obesity is associated with about 30% increased risk in all studies, but the proportion of obese people varies considerably from one country to another. Therefore, the proportion of cancer attributable to obesity could range from 3% to 16%. Numerous epidemiological studies confirmed that obesity is a risk factor of pancreatic cancer in obese men and women (BMI, kg/m2≥30.0), with a relative risk estimated to 1.76 (95% CI, 0.90-3.45) and 1.70 (95% CI, 1.09-2.64), respectively. As previously demonstrated by partners 9 and 10, obesity is associated with fat pancreatic infiltration and precancerous lesions, such as PanIN lesions in humans. Pancreatic lesions such as adipose infiltration, iron deposits, extent of fibrosis, acino-ductal metaplasia and Pan-IN are involved in pancreatic oncogenesis.

The goal of this study is to be able to diagnose early precancerous states in patients, such as acino-ductal metaplasia (and also PanIN lesions which are more frequently observed in humans,) inflammatory process (iron deposits, fibrosis lesions) and adipose involvement in the context of obesity and metabolic syndrome. Investigators hypothesis is that specific MR imaging sequences, adapted from previous studies in rodents, could be a relevant tool to diagnose early pancreatic lesions and follow their evolution in the context of obesity and metabolic syndrome.

To this aim, the investigators will conduct a study to assess the relevance of MR imaging sequences to diagnose specific pancreatic lesions in obese patients, validated at the microscopic level. The investigators will analyze MR imaging of obese patients (BMI>30)/non obese patients (BMI<25) with a planned pancreatic surgery. It will be possible to compare imaging with histology performed on resected parenchyma. The investigators propose a proof-of-concept study aiming at assessing the relevance of specific MR imaging to diagnose early pancreatic lesions in humans and in obese patients especially. MR imaging will be performed in both obese and non obese patients with a planned pancreatic surgery in hospital to resect a benign lesion (such as neuroendocrine tumour or IPMN...). MRI are performed in the normal course of care; their sequences will be adapted for this study. It will be possible to compare imaging with histology of the resected parenchyma.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 59
• Est. completion date: October 27, 2023
• Est. primary completion date: October 27, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 1st stage : Volunteers without history of known pancreatic disorders

• Adults

• 2nd stage : Obese Volunteers

• Adults with planned hepatic MRI

• Obese (BMI =30)

• 3rd stage : Patients

• Adults (aged 18-65 years) with a planned pancreatic surgery for benign pancreatic lesions (IPMN, cystic lesions or neuroendocrine tumors)

• Obese (BMI=30), overweight (25=BMI=29.9) or non-obese patients (18.5<BMI<24.9)

Exclusion Criteria:

For volunteers without history of known pancreatic disorders (1st stage):

• Symptoms or past medical history suggesting pancreatic disorders

For all participants (1st, 2nd and 3rd stages) :

• Patients with contraindication to MRI (pacemaker, claustrophobia…)

• Inability to undergo MRI due to weight excess

• Pregnant or breastfeeding woman

• Absence of free and informed consent

• Non affiliation to a social security regime or CMU

• Subject deprived of freedom, subject under a legal protective measure

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Radiation:
• MRI with additional sequences
MRI with 15 min additional sequences to validate and assess pancreatic MRI sequences
• MRI
MRI with 15 min additional sequences to validate and assess pancreatic MRI sequences

Procedure:
• Left pancreatectomy or pancreaticoduodenectomy
Histological analysis :

Radiation:
• MRI with additional sequences
MRI with 15 min additional sequences to assess the relevance of MRI to diagnose specific pancreatic lesions in obese patients

Locations

Country	Name	City	State
France	Hôpital Beaujon	Clichy
France	Hôpital Beaujon	Clichy

Sponsors (4)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Fondation ARC, Ligue contre le cancer, France, National Cancer Institute, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Quantitative MRI parameters	Pancreatic fat content	Day 1
Primary	Quantitative MRI parameters	Diffusion coefficients (10-4 mm2/s)	Day 1
Primary	Quantitative MRI parameters	transverse magnetization relaxation rate	Day 1
Primary	Quantitative MRI parameters	longitudinal relaxation rate	Day 1
Primary	Quantitative MRI parameters	visco-elastic parameters by measure of tissue stiffness (kPa)	Day 1
Primary	fibroinflammatory lesions at histology in obese patients	% surface of fibrosis	2 months
Primary	fibroinflammatory lesions at histology in obese patients	% surface of acinoductal metaplasia	2 months
Primary	fibroinflammatory lesions at histology in obese patients	number of acinoductal metaplasia lesions	2 months
Secondary	Histologic parameters	% surface of fat pancreatic infiltration	2 months
Secondary	Histologic parameters	% surface of iron deposit	2 months
Secondary	Histologic parameters	% surface of fibrosis	2 months
Secondary	Histologic parameters	% surface of acinoductal metaplasia	2 months
Secondary	Histologic parameters	number of PanIN lesions	2 months y
Secondary	MRI parameters	pancreatic fat content	Day 1
Secondary	MRI parameters	Diffusion coefficients (10-4 mm2/s)	Day 1
Secondary	MRI parameters	transverse magnetization relaxation rate	Day 1I
Secondary	MRI parameters	longitudinal magnetization relaxation rate	Day 1
Secondary	MRI parameters	visco-elastic parameters by measure of tissue stiffness (kPa)	Day 1
Secondary	Biomarkers of pathways activation measured by immunohistochemistry on resected pancreatic parenchyma	% expression of molecules involved in TGFb and orexin signaling	2 months
Secondary	Biomarkers of pathways activation measured by immunohistochemistry on resected pancreatic parenchyma	% expression of the markers in inflammatory cells (CD8, IL6, Caspase, HNF6)	2 months
Secondary	Biomarkers of pathways activation measured by immunohistochemistry on resected pancreatic parenchyma	% surface of acinoductal metaplasia	2 months
Secondary	Biomarkers of pathways activation measured by immunohistochemistry on resected pancreatic parenchyma	% of stained cells	2 months