NCT07817225

Brief Summary

Non-functioning pancreatic neuroendocrine tumors (NF-PanNETs) are heterogeneous neoplasms of the pancreatic endocrine tissue, displaying variable clinical behavior from indolent to highly aggressive forms. Their often asymptomatic nature and lack of reliable preoperative biomarkers make clinical management particularly challenging. This exploratory study will investigate cell-free DNA (cfDNA) as a potential non-invasive biomarker in NF-PanNETs. cfDNA samples from approximately 30 patients, representing distinct clinical courses (active surveillance, indolent post-surgical, and aggressive post-surgical cases), will be analyzed using advanced methylome and nucleosome footprinting techniques. The aim is to evaluate cfDNA's diagnostic and prognostic potential to improve disease monitoring and support personalized therapeutic strategies in NF-PanNET patients.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at below P25 for all trials

Timeline
14mo left

Started Sep 2026

Geographic Reach
1 country

1 active site

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress5%
Sep 2026Dec 2027

First Submitted

Initial submission to the registry

September 8, 2026

Completed
4 days until next milestone

Study Start

First participant enrolled

September 12, 2026

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 14, 2026

Completed
12 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 12, 2027

Expected
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 12, 2027

Last Updated

September 16, 2026

Status Verified

September 1, 2026

Enrollment Period

1 year

First QC Date

September 8, 2026

Last Update Submit

September 11, 2026

Conditions

Pancreatic Neuroendocrine Tumor

Keywords

cfDNAPanNETprognostic signaturesbiomarkerliquid biopsy

Outcome Measures

Primary Outcomes (1)

  • cfDNA Molecular Profiling

    To investigate the feasability of circulating-free DNA (cfDNA) assessment as a non- invasive biomarker for non-functioning pancreatic neuroendocrine tumors (NF-PanNETs). cfDNA concentrations and cfDNA epigenetic and fragmentomic signatures in plasma samples will be analysed.

    From enrollment until the day before surgery, or during scheduled visits for patients under active surveillance.

Secondary Outcomes (1)

  • Predictive Value of cfDNA for Tumor Aggressiveness

    From enrollment until the day before surgery, or during scheduled visits for patients under active surveillance.

Study Arms (3)

histological indolent PanNET

patients submitted to surgical resection for pancreatic neuroendocrine tumor (PanNET) with histopathological diagnosis of indolent disease

Other: cfDNA molecular profiling

histological aggressive PanNET

patients submitted to surgical resection for pancreatic neuroendocrine tumor (PanNET) with histopathological diagnosis of aggressive disease

Other: cfDNA molecular profiling

PanNET under active surveillance

patients currently under active surveillance for small indolent pancreatic neuroendocrine tumor (PanNET)

Other: cfDNA molecular profiling

Interventions

cfDNA molecular profilingOTHER

Circulating-free DNA (cfDNA) will be extracted from plasma samples previously collected and currently stored at the San Raffaele Hospital (HSR) NETBank biobank. cfDNA profiling will be performed using methylome and nucleosome footprinting techniques. No therapeutic or experimental intervention will be performed.

PanNET under active surveillancehistological aggressive PanNEThistological indolent PanNET

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

The study population will include approximately 30 adult patients diagnosed with non-functioning pancreatic neuroendocrine tumors (NF-PanNETs) whose biological samples are available through the HSR NETBank biobank. Participants will represent three distinct clinical subgroups: patients under active surveillance and patients who underwent surgical resection with a histopathological diagnosis of either indolent or aggressive disease. All included patients have provided informed consent for the use of their biological material and clinical data for research purposes.

You may qualify if:

  • Age ≥18 years.
  • Diagnosis of sporadic, well-differentiated, non-functioning pancreatic neuroendocrine tumor (NF-PanNET).
  • Signed informed consent for the use of plasma samples stored in the "NETbank" biobank.
  • Availability of pre-operative or surveillance plasma samples.

You may not qualify if:

  • Genetic syndromes associated with NF-PanNETs (e.g., MEN1, VHL).
  • Functioning PanNETs.
  • Inadequate quality or quantity of circulating-free DNA (cfDNA) extracted from plasma samples.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

IRCCS San Raffaele

Milan, MI, 20132, Italy

Location

Related Publications (8)

  • Loyfer N, Magenheim J, Peretz A, Cann G, Bredno J, Klochendler A, Fox-Fisher I, Shabi-Porat S, Hecht M, Pelet T, Moss J, Drawshy Z, Amini H, Moradi P, Nagaraju S, Bauman D, Shveiky D, Porat S, Dior U, Rivkin G, Or O, Hirshoren N, Carmon E, Pikarsky A, Khalaileh A, Zamir G, Grinbaum R, Abu Gazala M, Mizrahi I, Shussman N, Korach A, Wald O, Izhar U, Erez E, Yutkin V, Samet Y, Rotnemer Golinkin D, Spalding KL, Druid H, Arner P, Shapiro AMJ, Grompe M, Aravanis A, Venn O, Jamshidi A, Shemer R, Dor Y, Glaser B, Kaplan T. A DNA methylation atlas of normal human cell types. Nature. 2023 Jan;613(7943):355-364. doi: 10.1038/s41586-022-05580-6. Epub 2023 Jan 4.

    PMID: 36599988BACKGROUND

  • Vaisvila R, Ponnaluri VKC, Sun Z, Langhorst BW, Saleh L, Guan S, Dai N, Campbell MA, Sexton BS, Marks K, Samaranayake M, Samuelson JC, Church HE, Tamanaha E, Correa IR Jr, Pradhan S, Dimalanta ET, Evans TC Jr, Williams L, Davis TB. Enzymatic methyl sequencing detects DNA methylation at single-base resolution from picograms of DNA. Genome Res. 2021 Jul;31(7):1280-1289. doi: 10.1101/gr.266551.120. Epub 2021 Jun 17.

    PMID: 34140313BACKGROUND

  • Cowzer D, Shah RH, Chou JF, Kundra R, Punn S, Fiedler L, DeMore A, Capanu M, Berger MF, Reidy-Lagunes D, Raj N. Clinical utility of plasma cell-free DNA in pancreatic neuroendocrine neoplasms. Endocr Relat Cancer. 2024 Mar 4;31(4):e230292. doi: 10.1530/ERC-23-0292. Print 2024 Apr 1.

    PMID: 38252063BACKGROUND

  • Oversoe SK, Sorensen BS, Tabaksblat EM, Gronbaek H, Kelsen J. Cell-Free DNA and Clinical Characteristics in Patients with Small Intestinal or Pancreatic Neuroendocrine Tumors. Neuroendocrinology. 2022;112(1):43-50. doi: 10.1159/000514457. Epub 2021 Jan 18.

    PMID: 33461190BACKGROUND

  • Boons G, Vandamme T, Peeters M, Beyens M, Driessen A, Janssens K, Zwaenepoel K, Roeyen G, Van Camp G, Op de Beeck K. Cell-Free DNA From Metastatic Pancreatic Neuroendocrine Tumor Patients Contains Tumor-Specific Mutations and Copy Number Variations. Front Oncol. 2018 Nov 1;8:467. doi: 10.3389/fonc.2018.00467. eCollection 2018.

    PMID: 30443491BACKGROUND

  • Partelli S, Battistella A, Andreasi V, Muffatti F, Tamburrino D, Pecorelli N, Crippa S, Balzano G, Falconi M. Critical appraisal of the adequacy of surgical indications for non-functioning pancreatic neuroendocrine tumours. BJS Open. 2024 Jul 2;8(4):zrae083. doi: 10.1093/bjsopen/zrae083.

    PMID: 39107074BACKGROUND

  • Partelli S, Giannone F, Schiavo Lena M, Muffatti F, Andreasi V, Crippa S, Tamburrino D, Zamboni G, Rubini C, Doglioni C, Falconi M. Is the Real Prevalence of Pancreatic Neuroendocrine Tumors Underestimated? A Retrospective Study on a Large Series of Pancreatic Specimens. Neuroendocrinology. 2019;109(2):165-170. doi: 10.1159/000499606. Epub 2019 May 22.

    PMID: 31117106BACKGROUND

  • Dasari A, Shen C, Halperin D, Zhao B, Zhou S, Xu Y, Shih T, Yao JC. Trends in the Incidence, Prevalence, and Survival Outcomes in Patients With Neuroendocrine Tumors in the United States. JAMA Oncol. 2017 Oct 1;3(10):1335-1342. doi: 10.1001/jamaoncol.2017.0589.

    PMID: 28448665BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Plasma samples

MeSH Terms

Conditions

Adenoma, Islet Cell

Condition Hierarchy (Ancestors)

AdenomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsPancreatic NeoplasmsDigestive System NeoplasmsNeoplasms by SiteEndocrine Gland NeoplasmsDigestive System DiseasesPancreatic DiseasesEndocrine System Diseases

Study Officials

  • Stefano Partelli, MD, PhD

    IRCCS San Raffaele

    PRINCIPAL INVESTIGATOR

  • Daniela Cesana, PhD

    San Raffaele Telethon Institute for Gene Therapy

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
RETROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Director of Pancreatic and Transplant Surgery Unit

Study Record Dates

First Submitted

September 8, 2026

First Posted

September 14, 2026

Study Start

September 12, 2026

Primary Completion (Estimated)

September 12, 2027

Study Completion (Estimated)

December 12, 2027

Last Updated

September 16, 2026

Record last verified: 2026-09

Locations

IT(1)