Clinical trial NCT04370574: Discovery of Soluble Biomarkers for Pancreatic Cancer Using Innovative All-Patient Inclusive Methodology
Official title: Discovery of Soluble Biomarkers for Pancreatic Cancer Using Innovative All-Patient Inclusive Methodology (PanEXPEL2)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Pancreatic Neoplasms
Keywords: Biopsy
Fine-Needle
diagnostic imaging
Endosonography
Lead sponsor: University Hospital, Montpellier
Sponsor class: OTHER
First posted: 2020-05-01
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patient with pancreatic mass and suspicion of pancreatic ductal adenocarcinoma requiring endoscopic ultrasound with fine needle biopsy.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Predictive value of each protein contained in Cytolyt® for the positive diagnosis of pancreatic ductal adenocarcinoma
timeFrame: Baseline
Secondary outcomes:
measure: Disease-free survival
timeFrame: One year
measure: Disease-free survival
timeFrame: One year
measure: Overall survival
timeFrame: One year
measure: Identification of prognostically significant biomarkers
timeFrame: One year
Other outcomes:
Locations:
city: Montpellier
country: France
facility: Uh Montpellier
Study officials:
References: