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PDAC - Pancreatic Ductal AdenocarcinomaFORESIGHTNCT07224802

Forecasting Occult liveR Metastasis Using an Exosomal Signature for Intelligent Guided Hepatic Targeting

An observational study of PDAC - Pancreatic Ductal Adenocarcinoma, run by City of Hope Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Early liver metastasis (Early-LiM) is the most significant prognostic factor in pancreatic ductal adenocarcinoma (PDAC) and is thought to originate from occult micrometastases present at the time of surgery. Reliable preoperative detection of such lesions remains an unmet clinical need. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
PDAC - Pancreatic Ductal Adenocarcinoma
What is being tested?
EXELiM assay (qRT-PCR validation) and EXELiM small RNA sequencing
How many people
372 participants
Where
1 siteUnited States
Study dates
21 Jun 2024to 18 Feb 2026
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: Patients with histologically confirmed pancreatic ductal adenocarcinoma (PDAC) who have undergone curative-intent pancreatectomy with available preoperative plasma samples.

Who may be able to join

  • Histologically confirmed pancreatic ductal adenocarcinoma (PDAC)
  • Undergoing curative-intent pancreatectomy
  • Availability of preoperative plasma samples
  • Complete clinical and follow-up data
  • Written informed consent obtained

Who cannot join

  • Synchronous or secondary malignancies
  • Non-adenocarcinoma histology
  • Lack of informed consent
  • Incomplete plasma sample data

Trial locations and contacts

1 site in 1 country.

United States1 site

  • City of Hope Medical Center

    Duarte, California, 91016

Other trials in United States

About this study

Official title: An Exosome-based Liquid Biopsy Signature for Preoperative Identification of Occult Liver Metastasis in Patients With Pancreatic Ductal Adenocarcinoma

Early liver metastasis (Early-LiM) is the most significant prognostic factor in pancreatic ductal adenocarcinoma (PDAC) and is thought to originate from occult micrometastases present at the time of surgery. Reliable preoperative detection of such lesions remains an unmet clinical need.

The EXELiM study aims to develop and validate a circulating exosomal microRNA (exo-miRNA)-based liquid biopsy assay to accurately identify PDAC patients at high risk of occult liver metastasis before surgery. By integrating machine learning with multi-institutional plasma exosome profiling, this study seeks to enable biology-driven patient stratification and guide treatment sequencing toward precision oncology.

Read the detailed description

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest human malignancies, with a 5-year overall survival rate below 10%. Even after curative-intent pancreatectomy, over 70% of patients experience disease recurrence, with early liver metastasis (within six months postoperatively) representing the most aggressive and fatal pattern.

Emerging evidence indicates that pancreatic tumors release exosomes that modulate the liver microenvironment, establishing a premetastatic niche that facilitates early colonization. We hypothesize that circulating exosomal microRNAs reflect these biological processes and can serve as non-invasive biomarkers for detecting occult liver metastasis.

In this multi-center observational study, preoperative plasma-derived exosomes from PDAC patients are analyzed using next-generation small RNA sequencing and validated by RT-qPCR. A machine learning model is employed to integrate exo-miRNA expression profiles and clinical variables, yielding a predictive score for early liver metastasis risk.

The study evaluates the diagnostic accuracy, prognostic utility, and clinical benefit of the exo-miRNA panel compared to conventional biomarkers such as CA19-9.

Being tested
EXELiM assay (qRT-PCR validation), EXELiM small RNA sequencing
Keywords
pancreatic ductal adenocarcinoma, exosomal miRNA, early liver metastasis, liquid biopsy, exosome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EXELiM assay (qRT-PCR validation)Diagnostic test

    Quantitative reverse-transcription PCR (qRT-PCR)-based validation assay performed on preoperative plasma samples from PDAC patients in the training and validation cohorts.

    Candidate microRNAs identified by small RNA sequencing were tested using the EXELiM assay to validate their predictive accuracy for occult liver metastasis detection prior to surgery.

  • EXELiM small RNA sequencingDiagnostic test

    High-throughput small RNA sequencing performed on preoperative plasma samples from PDAC patients in the discovery cohort to identify exosome-derived microRNAs associated with occult liver metastasis or early postoperative hepatic recurrence.

Study groups in NCT07224802
Study groupRoleWhat they receive
Training Cohort - PDAC with Occult Liver MetastasisPatients with PDAC who were found to have occult liver metastases at the time of or shortly after curative-intent pancreatectomy (within 6 months post-surgery), in the first cohort (training set).
Receives: Diagnostic Test: EXELiM assay (qRT-PCR validation)
Training Cohort - PDAC without Occult Liver MetastasisPatients with PDAC who did not develop liver metastasis for at least 6 months after curative-intent surgery in the first cohort (training set).
Receives: Diagnostic Test: EXELiM assay (qRT-PCR validation)
Validation Cohort - PDAC with Occult Liver MetastasisPatients with PDAC who were found to have occult liver metastases (early postoperative hepatic recurrence within 6 months) in the second cohort (validation set).
Receives: Diagnostic Test: EXELiM assay (qRT-PCR validation)
Validation Cohort - PDAC without Occult Liver MetastasisPatients with PDAC who did not develop liver metastasis for at least 6 months after curative-intent surgery in the second cohort (validation set).
Receives: Diagnostic Test: EXELiM assay (qRT-PCR validation)
Discovery Cohort - PDAC with Occult Liver MetastasisPatients with PDAC who were found to have occult liver metastases at the time of or shortly after curative-intent pancreatectomy (within 6 months post-surgery), in the discovery cohort.
Receives: Diagnostic Test: EXELiM small RNA sequencing
Discovery Cohort - PDAC without Occult Liver MetastasisPatients with PDAC who did not develop liver metastasis for at least 6 months after curative-intent surgery in the discovery cohort.
Receives: Diagnostic Test: EXELiM small RNA sequencing

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Specificity

    True Negative Rate: probability of a negative test result conditioned on absence of early liver metastasis

    Measured: Through study completion, an average of 3 year

Secondary outcomes (2)

  1. Sensitivity

    True Positive Rate: probability of a positive test result conditioned on the presence of early liver metastasis

    Measured: Through study completion, an average of 3 year

  2. Area Under the Receiver Operating Characteristic Curve (AUC)

    Description: AUC representing the overall discriminative ability of the circRNA-based model.

    Measured: Through study completion, an average of 3 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Nov 2025
  2. Study start21 Jun 2024
  3. Primary completion18 Jan 2026
  4. Study completion18 Feb 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case-control
Time perspective
Retrospective
Enrolment
372 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07224802
Sponsor's protocol ID
19288/FORESIGHT
Acronym
FORESIGHT
Status last verified
Mar 2026
First submitted
3 Nov 2025
Last updated
13 Mar 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Data collected for the study will be made available to others, including de-identified participant data, at publication, via a signed data access agreement and at the discretion of the investigators' approval of the proposed use of such data.

Publications

  • Costa-Silva B, Aiello NM, Ocean AJ, Singh S, Zhang H, Thakur BK, Becker A, Hoshino A, Mark MT, Molina H, Xiang J, Zhang T, Theilen TM, Garcia-Santos G, Williams C, Ararso Y, Huang Y, Rodrigues G, Shen TL, Labori KJ, Lothe IM, Kure EH, Hernandez J, Doussot A, Ebbesen SH, Grandgenett PM, Hollingsworth MA, Jain M, Mallya K, Batra SK, Jarnagin WR, Schwartz RE, Matei I, Peinado H, Stanger BZ, Bromberg J, Lyden D. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat Cell Biol. 2015 Jun;17(6):816-26. doi: 10.1038/ncb3169. Epub 2015 May 18.

    PubMed 25985394

  • Hoshino A, Costa-Silva B, Shen TL, Rodrigues G, Hashimoto A, Tesic Mark M, Molina H, Kohsaka S, Di Giannatale A, Ceder S, Singh S, Williams C, Soplop N, Uryu K, Pharmer L, King T, Bojmar L, Davies AE, Ararso Y, Zhang T, Zhang H, Hernandez J, Weiss JM, Dumont-Cole VD, Kramer K, Wexler LH, Narendran A, Schwartz GK, Healey JH, Sandstrom P, Labori KJ, Kure EH, Grandgenett PM, Hollingsworth MA, de Sousa M, Kaur S, Jain M, Mallya K, Batra SK, Jarnagin WR, Brady MS, Fodstad O, Muller V, Pantel K, Minn AJ, Bissell MJ, Garcia BA, Kang Y, Rajasekhar VK, Ghajar CM, Matei I, Peinado H, Bromberg J, Lyden D. Tumour exosome integrins determine organotropic metastasis. Nature. 2015 Nov 19;527(7578):329-35. doi: 10.1038/nature15756. Epub 2015 Oct 28.

    PubMed 26524530

  • Bojmar L, Zambirinis CP, Hernandez JM, Chakraborty J, Shaashua L, Kim J, Johnson KE, Hanna S, Askan G, Burman J, Ravichandran H, Zheng J, Jolissaint JS, Srouji R, Song Y, Choubey A, Kim HS, Cioffi M, van Beek E, Sigel C, Jessurun J, Velasco Riestra P, Blomstrand H, Jonsson C, Jonsson A, Lauritzen P, Buehring W, Ararso Y, Hernandez D, Vinagolu-Baur JP, Friedman M, Glidden C, Firmenich L, Lieberman G, Mejia DL, Nasar N, Mutvei AP, Paul DM, Bram Y, Costa-Silva B, Basturk O, Boudreau N, Zhang H, Matei IR, Hoshino A, Kelsen D, Sagi I, Scherz A, Scherz-Shouval R, Yarden Y, Oren M, Egeblad M, Lewis JS, Keshari K, Grandgenett PM, Hollingsworth MA, Rajasekhar VK, Healey JH, Bjornsson B, Simeone DM, Tuveson DA, Iacobuzio-Donahue CA, Bromberg J, Vincent CT, O'Reilly EM, DeMatteo RP, Balachandran VP, D'Angelica MI, Kingham TP, Allen PJ, Simpson AL, Elemento O, Sandstrom P, Schwartz RE, Jarnagin WR, Lyden D. Multi-parametric atlas of the pre-metastatic liver for prediction of metastatic outcome in early-stage pancreatic cancer. Nat Med. 2024 Aug;30(8):2170-2180. doi: 10.1038/s41591-024-03075-7. Epub 2024 Jun 28.

    PubMed 38942992

  • Tang D, Wang D, Yuan Z, Xue X, Zhang Y, An Y, Chen J, Tu M, Lu Z, Wei J, Jiang K, Miao Y. Persistent activation of pancreatic stellate cells creates a microenvironment favorable for the malignant behavior of pancreatic ductal adenocarcinoma. Int J Cancer. 2013 Mar 1;132(5):993-1003. doi: 10.1002/ijc.27715. Epub 2012 Oct 5.

    PubMed 22777597

  • Grunwald B, Harant V, Schaten S, Fruhschutz M, Spallek R, Hochst B, Stutzer K, Berchtold S, Erkan M, Prokopchuk O, Martignoni M, Esposito I, Heikenwalder M, Gupta A, Siveke J, Saftig P, Knolle P, Wohlleber D, Kruger A. Pancreatic Premalignant Lesions Secrete Tissue Inhibitor of Metalloproteinases-1, Which Activates Hepatic Stellate Cells Via CD63 Signaling to Create a Premetastatic Niche in the Liver. Gastroenterology. 2016 Nov;151(5):1011-1024.e7. doi: 10.1053/j.gastro.2016.07.043. Epub 2016 Aug 6.

    PubMed 27506299

  • Houg DS, Bijlsma MF. The hepatic pre-metastatic niche in pancreatic ductal adenocarcinoma. Mol Cancer. 2018 Jun 14;17(1):95. doi: 10.1186/s12943-018-0842-9.

    PubMed 29903049

  • Lee JW, Stone ML, Porrett PM, Thomas SK, Komar CA, Li JH, Delman D, Graham K, Gladney WL, Hua X, Black TA, Chien AL, Majmundar KS, Thompson JC, Yee SS, O'Hara MH, Aggarwal C, Xin D, Shaked A, Gao M, Liu D, Borad MJ, Ramanathan RK, Carpenter EL, Ji A, de Beer MC, de Beer FC, Webb NR, Beatty GL. Hepatocytes direct the formation of a pro-metastatic niche in the liver. Nature. 2019 Mar;567(7747):249-252. doi: 10.1038/s41586-019-1004-y. Epub 2019 Mar 6.

    PubMed 30842658

  • Chikhladze S, Lederer AK, Kousoulas L, Reinmuth M, Sick O, Fichtner-Feigl S, Wittel UA. Adjuvant chemotherapy after surgery for pancreatic ductal adenocarcinoma: retrospective real-life data. World J Surg Oncol. 2019 Nov 9;17(1):185. doi: 10.1186/s12957-019-1732-3.

    PubMed 31706323

  • Merkow RP, Bilimoria KY, Tomlinson JS, Paruch JL, Fleming JB, Talamonti MS, Ko CY, Bentrem DJ. Postoperative complications reduce adjuvant chemotherapy use in resectable pancreatic cancer. Ann Surg. 2014 Aug;260(2):372-7. doi: 10.1097/SLA.0000000000000378.

    PubMed 24374509

  • Powell-Brett S, Pande R, Roberts KJ. Achieving 'Marginal Gains' to Optimise Outcomes in Resectable Pancreatic Cancer. Cancers (Basel). 2021 Apr 1;13(7):1669. doi: 10.3390/cancers13071669.

    PubMed 33916294

  • Zambirinis CP, Midya A, Chakraborty J, Chou JF, Zheng J, McIntyre CA, Koszalka MA, Wang T, Do RK, Balachandran VP, Drebin JA, Kingham TP, D'Angelica MI, Allen PJ, Gonen M, Simpson AL, Jarnagin WR. Recurrence After Resection of Pancreatic Cancer: Can Radiomics Predict Patients at Greatest Risk of Liver Metastasis? Ann Surg Oncol. 2022 Aug;29(8):4962-4974. doi: 10.1245/s10434-022-11579-0. Epub 2022 Apr 3.

    PubMed 35366706

  • Seelen LWF, Floortje van Oosten A, Brada LJH, Groot VP, Daamen LA, Walma MS, van der Lek BF, Liem MSL, Patijn GA, Stommel MWJ, van Dam RM, Koerkamp BG, Busch OR, de Hingh IHJT, van Eijck CHJ, Besselink MG, Burkhart RA, Borel Rinkes IHM, Wolfgang CL, Molenaar IQ, He J, van Santvoort HC. Early Recurrence After Resection of Locally Advanced Pancreatic Cancer Following Induction Therapy: An International Multicenter Study. Ann Surg. 2023 Jul 1;278(1):118-126. doi: 10.1097/SLA.0000000000005666. Epub 2022 Aug 11.

    PubMed 35950757

  • Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A. Cancer statistics, 2025. CA Cancer J Clin. 2025 Jan-Feb;75(1):10-45. doi: 10.3322/caac.21871. Epub 2025 Jan 16.

    PubMed 39817679

  • McGuigan A, Kelly P, Turkington RC, Jones C, Coleman HG, McCain RS. Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes. World J Gastroenterol. 2018 Nov 21;24(43):4846-4861. doi: 10.3748/wjg.v24.i43.4846.

    PubMed 30487695

  • Kleeff J, Korc M, Apte M, La Vecchia C, Johnson CD, Biankin AV, Neale RE, Tempero M, Tuveson DA, Hruban RH, Neoptolemos JP. Pancreatic cancer. Nat Rev Dis Primers. 2016 Apr 21;2:16022. doi: 10.1038/nrdp.2016.22.

    PubMed 27158978

Questions about this trial

What is this clinical trial studying?

An observational study of PDAC - Pancreatic Ductal Adenocarcinoma, run by City of Hope Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Specificity (time frame: Through study completion, an average of 3 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07224802, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2026; AzTrials last refreshed its copy on 26 Oct 2026.

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