An Exosome-based and Machine-learning-powered Liquid Biopsy for Pancreatic Cancer Early-detection and Disease Monitoring
| Registry | NCT07700992, acronym PANXEON |
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| Status | Recruiting |
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| Study type | Observational |
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| Enrollment | 600 (Estimated) |
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| Sponsor | Università Vita-Salute San Raffaele (Other) |
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| 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 |
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| Interventions | PANXEON (Diagnostic test) |
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| Dates | start 2026-06-03, primary completion 2031-12-31 (estimated), completion 2032-01-30 (estimated), first posted 2026-07-14, last updated 2026-07-14 |
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| Locations | 1 site in Italy |
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Related Papers Related Patents Related Grants Related Experts
All trials for Familial Pancreatic Cancer All trials for Familial Pancreatic Carcinoma All trials of PANXEON
-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
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+Detailed description
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-including individuals with hereditary or familial pancreatic cancer and those with mucinous pancreatic cystic lesions-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, with the hypothesis that combined microRNA profiling can improve molecular risk stratification and potentially anticipate disease progression compared with standard imaging-based surveillance alone. The study population will include adult men and women (≥18 years) at increased risk for PDAC due to familial or hereditary predisposition or mucinous pancreatic cysts, with generally stable health status and existing clinical follow-up; no vulnerable populations are specifically targeted.
No medicinal products or medical devices are administered in this study. The procedure under investigation consists exclusively of laboratory-based measurement of microRNA expression from previously collected plasma samples, using validated exosome isolation and quantification techniques, with no impact on clinical management. Available preliminary and published data demonstrate that combined cell-free and exosomal microRNA signatures can detect early-stage PDAC with high accuracy and show dynamic behavior during disease progression and treatment, supporting their relevance for risk stratification and disease monitoring. Clinical, demographic, and laboratory data will be retrieved.
+Arms and interventions
| Arm | Type | Interventions | Description |
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| Familial pancreatic cancer (FPC) | | Diagnostic Test: PANXEON | 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 |
| Hereditary pancreatic cancer (HPC) | | Diagnostic Test: PANXEON | 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 |
| Mucinous Pancreatic Neoplasms (MPN) | | Diagnostic Test: PANXEON | 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) |
- PANXEON (Diagnostic test): A panel of circulating microRNA, whose expression level is tested in cell-free and exosome-derived samples
+Outcome measures
Primary outcomes
- Sensitivity [Through study completion, an average of 1 year]: True positive rate: the probability of a positive test result, conditioned on the individual truly being positive
Secondary outcomes
- Specificity [Through study completion, an average of 1 year]: True negative rate: the probability of a negative test result, conditioned on the individual truly being negative
- 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]: A measure of trueness: proportion of correct predictions (both true positives and true negatives) among the total number of cases examined
+Eligibility
Sex: All, ages: 18 Years to 99 Years
Inclusion Criteria:
* 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
Exclusion Criteria:
* 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.
+Locations (1)
| Facility | City | Country | Status |
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| IRCCS San Raffaele Hospital | Milan, MI | Italy | Recruiting |
+Publications
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Results publication: 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
- Results publication: 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
- Results publication: 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
+Investigators