A Liquid Biopsy for Pancreatic Cancer Early-detection and Disease Monitoring

NCT07700992 | Recruiting

• 1 other identifier: PANXEON/2026
• Study Type: observational
• Target: 600
• Locations: 1 country
• Sites: 1

Brief Summary

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy characterized by an asymptomatic early phase, late diagnosis, and poor survival, particularly in individuals who develop disease outside the context of early-stage detection. Early detection strategies are currently limited to imaging-based surveillance (MRI and endoscopic ultrasound) in selected high-risk populations, but these approaches are invasive, costly, and suboptimal in sensitivity. The aim of this study is to evaluate circulating cell-free and exosome-bound microRNAs as non-invasive biomarkers of PDAC risk and disease biology

Conditions

Familial Pancreatic Cancer; Familial Pancreatic Carcinoma; Hereditary Pancreatic Cancer; Hereditary Pancreatitis; Pancreas Cancer; Pancreas Neoplasm; Pancreas Adenocarcinoma; Pancreas Cyst; Pancreatic Neoplasms; Intraductal Papillary Mucinous Neoplasm

Keywords

Early detection; Liquid biopsy

Outcome Measures

Primary Outcomes (1)

• Sensitivity

  True positive rate: the probability of a positive test result, conditioned on the individual truly being positive

  Through study completion, an average of 1 year

Secondary Outcomes (2)

• Specificity

  Through study completion, an average of 1 year

• Proportion of correct predictions (true positives and true negatives) among the total number of cases (i.e., accuracy)

  Through study completion, an average of 1 year

Study Arms (3)

Familial pancreatic cancer (FPC)

This term refers to individuals who are at a higher risk of developing pancreatic cancer based on their family history. There are two main risk categories: * 2 relatives with pancreatic cancer, who are first-degree relative of each other, and at least one should be a first degree relative of the individual for whom surveillance is being considered * 3 or more relatives with pancreatic cancer, regardless of the degree

Diagnostic Test: PANXEON

Hereditary pancreatic cancer (HPC)

This terms encompasses all individuals who are at an increased risk of developing pancreatic cancer based on the presence of a pathogenic (or likely pathogenic) germline variant. More specifically: * All individuals with a pathogenic (or likely pathogenic) germline variant in Serine/Threonine Kinase 11 (STK11), cyclin-dependent kinase inhibitor 2A (CDKN2A), Ataxia-Telangiectasia Mutated (ATM), and Breast cancer type 2 (BRCA2) genes, regardless of their family history of pancreatic cancer * Individuals who have both (i) a pathogenic (or likely pathogenic) germline variant in Breast cancer type 1 (BRCA1), Partner and Localizer of BRCA2 (PALB2), Mutator L Homolog 1 (MLH1), Mutator S Homolog 2 (MSH2), Mutator S Homolog 6 (MSH6), Postmeiotic Segregation 1 Homolog 2 (PMS2), or Epithelial Cell Adhesion Molecule (EPCAM) genes; and (ii) at least one relative diagnosed with pancreatic cancer

Diagnostic Test: PANXEON

Mucinous Pancreatic Neoplasms (MPN)

This term refers collectively to cystic lesions of the pancreas that confer an increased risk of developing pancreatic cancer. Collectively, this term encompasses both Intraductal Pancreatic Mucinous Neoplasms (IPMN) and Mucinous Cystic Neoplasias (MCNs)

Diagnostic Test: PANXEON

Interventions

PANXEON DIAGNOSTIC_TEST

A panel of circulating microRNA, whose expression level is tested in cell-free and exosome-derived samples

Familial pancreatic cancer (FPC); Hereditary pancreatic cancer (HPC); Mucinous Pancreatic Neoplasms (MPN)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Selection of participants will be equitable and non-discriminatory, with no exclusion based on sex, ethnicity, or socioeconomic status. Pediatric populations are excluded due to the rarity of PDAC risk conditions in this group and the absence of relevant stored biospecimens.

You may qualify if:

• Adult men or women aged ≥18 years at the time of plasma sample collection.
• Classification as at increased risk for pancreatic ductal adenocarcinoma (PDAC) due to familial pancreatic cancer or hereditary pancreatic cancer syndrome
• Classification as at increased risk for pancreatic ductal adenocarcinoma (PDAC) due to the presence of one (or more) mucinous pancreatic cystic lesion(s).
• Availability of stored plasma samples collected as part of routine clinical care or surveillance and archived in the institutional biobank.
• Availability of relevant clinical and demographic data in institutional medical records sufficient to address study objectives.
• Prior provision of informed consent for biobanking and research use of biological samples and data

You may not qualify if:

• Absence or insufficient quality/quantity of stored plasma samples for laboratory analysis.
• Lack of clinical data required for cohort classification and/or outcome assessment.
• History of pancreatic surgery or interventional procedures prior to plasma sample collection.
• Concurrent active malignancy at the time of sample collection, other than non-melanoma skin cancer.
• Samples collected outside routine clinical care or not compliant with institutional biobanking and data protection policies.

Sponsors & Collaborators

• Università Vita-Salute San Raffaele: lead

Study Sites (1)

IRCCS San Raffaele Hospital

Milan, MI, 20132, Italy

RECRUITING

Related Publications (20)

• Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263. doi: 10.3322/caac.21834. Epub 2024 Apr 4.

  PMID: 38572751 BACKGROUND

• Henrikson NB, Aiello Bowles EJ, Blasi PR, Morrison CC, Nguyen M, Pillarisetty VG, Lin JS. Screening for Pancreatic Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2019 Aug 6;322(5):445-454. doi: 10.1001/jama.2019.6190.

  PMID: 31386140 BACKGROUND

• Rahib L, Wehner MR, Matrisian LM, Nead KT. Estimated Projection of US Cancer Incidence and Death to 2040. JAMA Netw Open. 2021 Apr 1;4(4):e214708. doi: 10.1001/jamanetworkopen.2021.4708.

  PMID: 33825840 BACKGROUND

• Singhi AD, Koay EJ, Chari ST, Maitra A. Early Detection of Pancreatic Cancer: Opportunities and Challenges. Gastroenterology. 2019 May;156(7):2024-2040. doi: 10.1053/j.gastro.2019.01.259. Epub 2019 Feb 2.

  PMID: 30721664 BACKGROUND

• Zhao B, Zhao B, Chen F. Diagnostic value of serum carbohydrate antigen 19-9 in pancreatic cancer: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol. 2022 Sep 1;34(9):891-904. doi: 10.1097/MEG.0000000000002415. Epub 2022 Jul 27.

  PMID: 35913776 BACKGROUND

• Majumder S, Taylor WR, Foote PH, Berger CK, Wu CW, Mahoney DW, Bamlet WR, Burger KN, Postier N, de la Fuente J, Doering KA, Lidgard GP, Allawi HT, Petersen GM, Chari ST, Ahlquist DA, Kisiel JB. High Detection Rates of Pancreatic Cancer Across Stages by Plasma Assay of Novel Methylated DNA Markers and CA19-9. Clin Cancer Res. 2021 May 1;27(9):2523-2532. doi: 10.1158/1078-0432.CCR-20-0235. Epub 2021 Feb 16.

  PMID: 33593879 BACKGROUND

• Mannucci A, Hernandez G, Uetake H, Yamada Y, Balaguer F, Baba H, Chen T, Chen J, Boland CR, Cavestro GM, Quintero E, Goel A. Prediction of long-term recurrence-free and overall survival in early-onset colorectal cancer: the ENCORE multi-centre study. NPJ Precis Oncol. 2025 Jun 21;9(1):202. doi: 10.1038/s41698-025-00978-7.

  PMID: 40544180 BACKGROUND

• Miyoshi J, Mannucci A, Scarpa M, Gao F, Toden S, Whitsett T, Inge LJ, Bremner RM, Takayama T, Cheng Y, Bottiglieri T, Nagtegaal ID, Shrubsole MJ, Zaidi AH, Wang X, Coleman HG, Anderson LA, Meltzer SJ, Goel A; FINBAR-EMERALD collaborative group. Liquid biopsy to identify Barrett's oesophagus, dysplasia and oesophageal adenocarcinoma: the EMERALD multicentre study. Gut. 2025 Jan 17;74(2):169-181. doi: 10.1136/gutjnl-2024-333364.

  PMID: 39562048 BACKGROUND

• Xu C, Mannucci A, Esposito F, Oliveres H, Alonso-Orduna V, Yubero A, Fernandez-Martos C, Salud A, Gallego J, Martin-Richard M, Fernandez-Plana J, Guillot M, Aparicio J, Fakih M, Kopetz S, Feliu J, Maurel J, Goel A. An Exosome-Based Liquid Biopsy Predicts Depth of Response and Survival Outcomes to Cetuximab and Panitumumab in Metastatic Colorectal Cancer: The EXONERATE Study. Clin Cancer Res. 2025 Mar 17;31(6):1002-1015. doi: 10.1158/1078-0432.CCR-24-1934.

  PMID: 39820673 BACKGROUND

• Mannucci A, Balaguer F, Yamada Y, Nagasaka T, Toiyama Y, Okugawa Y, Marti-Gallostra M, Jimenez-Toscano M, Vidal-Tocino R, Jimenez F, Perea J, Quintero E, Boland CR, Cavestro GM, Goel A; SECOC-ENCODER Collaborators. An Exosome-Based Liquid Biopsy for the Detection of Early-Onset Colorectal Cancer: The ENCODER Multicenter Study. Gastroenterology. 2026 Feb;170(2):330-343. doi: 10.1053/j.gastro.2025.08.013. Epub 2025 Dec 9.

  PMID: 41364052 BACKGROUND

• Pepe MS, Etzioni R, Feng Z, Potter JD, Thompson ML, Thornquist M, Winget M, Yasui Y. Phases of biomarker development for early detection of cancer. J Natl Cancer Inst. 2001 Jul 18;93(14):1054-61. doi: 10.1093/jnci/93.14.1054. No abstract available.

  PMID: 11459866 BACKGROUND

• Mannucci A, Puzzono M, Frattura A, Prina D, Arcidiacono PG, Cavestro GM. Novel approaches to liquid biopsy in pancreatic cancer. Dig Liver Dis. 2026 Jul 4:S1590-8658(26)00774-7. doi: 10.1016/j.dld.2026.06.008. Online ahead of print. No abstract available.

  PMID: 42401515 BACKGROUND

• Takahashi T, Mannucci A, Shigeyasu K, Kopetz S, Fakih M, Maurel J, Fujiwara T, Goel A. EXONERATE-TRaCE: A Liquid Biopsy for Tracking Response to Anti-Epidermal Growth Factor Receptor-Based Therapy in Metastatic Colorectal Cancer. JCO Precis Oncol. 2026 May;10(5):e2501229. doi: 10.1200/PO-25-01229. Epub 2026 May 18.

  PMID: 42150147 BACKGROUND

• Mannucci A, Goel A. Reply. Gastroenterology. 2026 Jul;171(1):199-200. doi: 10.1053/j.gastro.2026.03.004. Epub 2026 Mar 14. No abstract available.

  PMID: 41839380 BACKGROUND

• Noma T, Saez de Gordoa K, Daca-Alvarez M, Miyazaki K, Wada Y, Mannucci A, Onoyama T, Shimada M, Cuatrecasas M, Bujanda L, Pellise M, Goel A; part of the EpiT1 Consortium. A machine learning-based transcriptomic signature for predicting tumor recurrence after curative resection in T1 colorectal cancer: a retrospective multicenter cohort study (The Tw1CE trial). Int J Surg. 2026 Jan 28;112(4):9039-51. doi: 10.1097/JS9.0000000000004690. Online ahead of print.

  PMID: 41604539 BACKGROUND

• Zaffaroni G, Mannucci A, Koskenvuo L, de Lacy B, Maffioli A, Bisseling T, Half E, Cavestro GM, Valle L, Ryan N, Aretz S, Brown K, Buttitta F, Carneiro F, Claber O, Blanco-Colino R, Collard M, Crosbie E, Cunha M, Doulias T, Fleming C, Heinrich H, Huneburg R, Metras J, Nagtegaal I, Negoi I, Nielsen M, Pellino G, Ricciardiello L, Sagir A, Sanchez-Guillen L, Seppala TT, Siersema P, Striebeck B, Sampson JR, Latchford A, Parc Y, Burn J, Moslein G. Updated European guidelines for clinical management of familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), gastric adenocarcinoma, proximal polyposis of the stomach (GAPPS) and other rare adenomatous polyposis syndromes: a joint EHTG-ESCP revision. Br J Surg. 2024 May 3;111(5):znae070. doi: 10.1093/bjs/znae070.

  PMID: 38722804 BACKGROUND

• Mannucci A, Zuppardo RA, Crippa S, Carrera P, Patricelli MG, Russo Raucci A, Calabrese F, Lazarevic D, Giannese F, Tonon G, Ferrari M, Testoni PA, Cavestro GM. MSH6 gene pathogenic variant identified in familial pancreatic cancer in the absence of colon cancer. Eur J Gastroenterol Hepatol. 2020 Mar;32(3):345-349. doi: 10.1097/MEG.0000000000001617.

  PMID: 31851094 BACKGROUND

• Mannucci A, Goel A. Advances in pancreatic cancer early diagnosis, prevention, and treatment: The past, the present, and the future. CA Cancer J Clin. 2026 Jan-Feb;76(1):e70035. doi: 10.3322/caac.70035. Epub 2025 Sep 19.

  PMID: 40971231 RESULT

• Paiella S, Capurso G, Carrara S, Secchettin E, Casciani F, Frigerio I, Zerbi A, Archibugi L, Bonifacio C, Malleo G, Cavestro GM, Barile M, Larghi A, Assisi D, Fantin A, Milanetto AC, Fabbri C, Casadei R, Donato G, Sassatelli R, De Marchi G, Di Matteo FM, Arcangeli V, Panzuto F, Puzzono M, Dal Buono A, Pezzilli R, Salvia R, Rizzatti G, Casadio M, Franco M, Butturini G, Pasquali C, Coluccio C, Ricci C, Cicchese N, Sereni G, de Pretis N, Stigliano S, Rudnas B, Marasco M, Lionetto G, Arcidiacono PG, Terrin M, Crovetto A, Mannucci A, Laghi L, Bassi C, Falconi M. Outcomes of a 3-Year Prospective Surveillance in Individuals at High Risk of Pancreatic Cancer. Am J Gastroenterol. 2024 Apr 1;119(4):739-747. doi: 10.14309/ajg.0000000000002546. Epub 2023 Oct 3.

  PMID: 37787643 RESULT

• Mannucci A, Cavestro GM, Goel A. A DEF perspective on the METAPAC study. Lancet Gastroenterol Hepatol. 2025 Oct;10(10):879. doi: 10.1016/S2468-1253(25)00191-8. No abstract available.

  PMID: 40914176 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma samples

MeSH Terms

Conditions

Pancreatic carcinoma, familial; Hereditary pancreatitis; Pancreatic Neoplasms; Pancreatic Cyst

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Cysts

Study Officials

• Alessandro Mannucci, MD

  Università Vita-Salute San Raffaele

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alessandro Mannucci, MD

CONTACT

0226437262; mannucci.alessandro@hsr.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator (AIRCS Start-Up #32233)

Study Record Dates

• First Submitted: July 8, 2026
• First Posted: July 14, 2026
• Study Start: June 3, 2026
• Primary Completion (Estimated): December 31, 2031
• Study Completion (Estimated): January 30, 2032
• Last Updated: July 14, 2026

Record last verified: 2026-07

Locations

IT (1)