Discovery of Soluble Biomarkers for Pancreatic Cancer Using Innovative All-Patient Inclusive Methodology (PanEXPEL2)

Discovery of Soluble Biomarkers for Pancreatic Cancer Using Innovative All-Patient Inclusive Methodology (PanEXPEL2)

Pancreatic ductal adenocarcinoma (PDAC) remains among cancers with a very poor prognosis (1-year survival <20%). Endoscopic ultrasound with fine needle aspiration (EUS/FNA) is the common examination for all patients with suspicious pancreatic mass. A method was recently developed : it preserves the sanitary sample, named EXPEL, which allows standard pathology examination and OMICS analyzes from the "rinse" liquid. After EUS/FNA in clinical practice, the content of the needle is rinsed in CytoLyt® preservative solution. After cytofiltration, this liquid is systematically discarded.

Based on the EXPEL concept, we hypothesise that this all-patients inclusive approach ("Modified EXPEL" procedure) combined with the methodology to access proteomic and metabolomics information in these original samples will allow us to identify a series of clinically useful marker signatures that will ultimately be measurable, non-invasively, in the patient blood.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Neoplasms
• Intervention / Treatment: Diagnostic test: Soluble Biomarkers dosage

Detailed Description

Clinical and pathological data will be prospectively collected to obtain 2 subgroups: PDAC and non-PDAC according to the final biopsy diagnosis. A combined quantitative analysis of the proteins and their peptides contained in CytoLyt® will be performed. ROC curves, AUC, sensitivity, specificity, positive predictive value and negative predictive value associated to biomarkers will be calculated to isolate combinations of diagnostic biomarkers. Candidate biomarkers will be validated by immunohistochemistry and multiple reaction monitoring. Prognostic biomarkers will be evaluated by generating 1-year overall survival curves and Cox regression.

The present research, modeled on current practice, employs novel and holistic approach - PANEXPEL methodology - to establish a new repertoire of biomarkers for pancreatic cancer. We intent to provide a comprehensive proteomic and metabolomics biomarker signature that will be measurable in the patient blood using common clinical methods. The potential for translation "from benchside to bedside" is especially high due to the involvement of clinical teams. We expect to propose a combined, robust protein/metabolite biomarker signature that can be rapidly tested in the clinics.

Necessary biological resources: Biological resources will include Cytolyt® and Blood Samples, accompanied by a signed Free and Informed Consent for each included patient.

1. CytoLyt® fluid will be first processed by Pathology Dept. of the CHU for routine PDAC diagnosis. In essence, the samples are filtered, tissue fragments and cells are kept for analysis while flow-through is kept until the diagnosis is confirmed. Once this is completed, the samples will be transferred to the lab where the proteins found in the CytoLytR fluid will be precipitated and then solubilized. The protein extracts are stored at -80°C pending proteomic analysis. The remaining CytoLytR fluid supernatant is also stored at - 80°C to be used for metabolomics.
2. Blood sample will be collected from each patient that underwent diagnostic biopsy. Dry tube for serum analysis 5 ml will be collected at the time of inclusion during the routine blood test (mandatory assessment pre-operative or pre-chemotherapy). The blood sample is centrifuged at 1500xg for 15 minutes while the resulting sera are aliquoted (500μl/aliquot; 4-5 aliquots per patient) and stored at -80°C. These samples will be stored at Biologic Resources Center (CRB Montpellier) that is labelled NF-S-96900 (AFNOR). The serum samples are intended for the validation phase (WP4) and will be exclusively dedicated to this study.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Régis SOUCHE, MD; Phone Number: +33467337069; Email: fr-souche@chu-montpellier.fr
• Study Contact Backup: Name: Eric ASSENAT, MDPhD; Phone Number: +33467330137; Email: e-assenat@chu-montpellier.fr

Study Locations

• France
  • Montpellier, France, 34280
    • Recruiting
    • UH Montpellier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patient with pancreatic mass and suspicion of pancreatic ductal adenocarcinoma requiring endoscopic ultrasound with fine needle biopsy.

Description

Inclusion Criteria:

• Patient with pancreatic mass and suspicion of pancreatic ductal adenocarcinoma requiring endoscopic ultrasound with fine needle biopsy

Exclusion Criteria:

• Vulberable person according to L1121-6 of Public health reglementation in France
• Pregnant women

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Predictive value of each protein contained in Cytolyt® for the positive diagnosis of pancreatic ductal adenocarcinoma	Predictive value of each protein contained in Cytolyt® for the positive diagnosis of pancreatic ductal adenocarcinoma Correlation with positive diagnosis of pancreatic ductal adenocarcinoma and proteins quantity in Cytolyt® samples using ROC curves (sensibility/specificity: Area Under the Curve > 0.85) and binary logistic regression method with controlling for the effects of the co-variates (such as age, disease cTNM stage, and treatment details).	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival	Disease-free survival (percentage of patients without recurrence) .Biomarkers that are prognostically significant on disease free or overall survival in patients with pancreatic cancer, identified using the survival analysis	One year
Disease-free survival	Biomarkers that are prognostically significant on disease free or overall survival in patients with pancreatic cancer, identified using the survival analysis. Disease-free survival (DFS) (time from diagnosis to time of first radiological evidence of local, regional, or distant relapse, or death due to any cause)	One year
Overall survival	Biomarkers that are prognostically significant on disease free or overall survival in patients with pancreatic cancer, identified using the survival analysis Overall survival at 1 year (percentage of patients alive)	One year
Identification of prognostically significant biomarkers	Biomarkers that are prognostically significant on disease free or overall survival in patients with pancreatic cancer, identified using the survival analysis. Kaplan Meier analysis, logrank test and Cox's proportional hazards regression model to identify biomarkers that are prognostically significant (Hazard ratio (HR) and its 95% confidence interval (CI)	One year

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2021
• Primary Completion (Anticipated): September 1, 2023
• Study Completion (Anticipated): June 1, 2024

Study Registration Dates

• First Submitted: April 28, 2020
• First Submitted That Met QC Criteria: April 28, 2020
• First Posted (Actual): May 1, 2020

Study Record Updates

• Last Update Posted (Actual): May 3, 2023
• Last Update Submitted That Met QC Criteria: May 2, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Biopsy; diagnostic imaging; Endosonography; Fine-Needle
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: RECHMPL20_0191

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No