Plasma cfDNA Fragmentomics for Early pNET Detection and Differential Diagnosis of Solid Pancreatic Tumors

NCT05847855 | Recruiting DMC

• 1 other identifier: CSPAC-NEN-4
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 2

Brief Summary

This prospective study aims to evaluate the sensitivity and specificity of an integrated model using fragmentomic profiles of plasma cell-free DNA for early detection of pancreatic neuroendocrine tumors and differential diagnosis of solid pancreatic tumors.

Conditions

Pancreatic Neuroendocrine Tumor; Solid Pancreatic Neoplasms

Keywords

Pancreatic neuroendocrine tumor; cell-free DNA; fragmentomics; early detection; Solid pancreatic neoplasms

Outcome Measures

Primary Outcomes (2)

• Sensitivity and specificity of the integrated fragmentomic model for detecting pNETs

  Sensitivity and specificity of the integrated model using fragmentomic profiles of plasma cfDNA for early detection of pNETs

  From date of first blood draw until first documented pNETs diagnosis, assessed up to 3 years.

• Sensitivity and specificity of the model for differential diagnosis among solid pancreatic tumors

  Sensitivity and specificity of the model for differential diagnosis among PDAC, pNET and SPT.

  From first blood draw until histopathological diagnosis, up to 3 years

Secondary Outcomes (2)

• Positive predictive value and negative predictive value

  From date of first blood draw until first documented pNETs diagnosis, assessed up to 3 years

• Accuracy of the model in predicting AJCC stage (where applicable) and tumor grade

  From date of first blood draw until first documented histopathological diagnosis, assessed up to 3 years

Study Arms (4)

pNETs

Patients with pancreatic neuroendocrine tumors (pNETs). The prospective cases enrolled by the sub-center shall strictly comply with the study's inclusion/exclusion criteria, consistent with the main center, and no independent adjustment of the enrollment criteria is allowed.

Diagnostic Test: Blood collection

Healthy

Healthy volunteers. The prospective cases enrolled by the sub-center shall strictly comply with the study's inclusion/exclusion criteria, consistent with the main center, and no independent adjustment of the enrollment criteria is allowed.

Diagnostic Test: Blood collection

PDAC

Patients with pancreatic ductal adenocarcinoma (PDAC) . The prospective cases enrolled by the sub-center shall strictly comply with the study's inclusion/exclusion criteria, consistent with the main center, and no independent adjustment of the enrollment criteria is allowed.

Diagnostic Test: Blood collection

SPT

Patients with solid pseudopapillary tumor (SPT) of pancreas. The prospective cases enrolled by the sub-center shall strictly comply with the study's inclusion/exclusion criteria, consistent with the main center, and no independent adjustment of the enrollment criteria is allowed.

Diagnostic Test: Blood collection

Interventions

Blood collection DIAGNOSTIC_TEST

Blood collection for fragmentomic profiles of plasma cell-free DNA. The sub-center shall use the same blood collection consumables (EDTA anticoagulant vacutainer tubes) and blood collection volume (10ml) as the main center; plasma separation shall be completed within 2 hours after blood collection, and all operations shall comply with the study's unified SOP.

Healthy; PDAC; SPT; pNETs

Eligibility Criteria

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

Study Population

The study population enrolled by the main center and the sub-center is uniformly divided into four groups with the same enrollment criteria for all. 1. pNET Group: Not receiving anti-tumor treatment before surgery, and were histopathologically confirmed pancreatic neuroendocrine tumors. 2. PDAC group: Patients with histopathologically confirmed pancreatic ductal adenocarcinoma (PDAC) who have not received any anti-tumor treatment before surgery. 3. SPT group: Patients with histopathologically confirmed solid pseudopapillary tumor (SPT) of the pancreas who have not received any anti-tumor treatment before surgery. 4. Healthy group: Healthy volunteers without a history of tumors and no pancreatic organic diseases.

You may qualify if:

• Age 18 and above, regardless of gender;
• Histopathological diagnosis with non-functional pancreatic neuroendocrine tumor, pancreatic ductal adenocarcinoma or solid pseudopapillary tumor;
• Not receiving any anti-tumor treatment before surgery, including chemotherapy, embolization, ablation, radiotherapy, and molecular targeted therapy;
• No obvious surgical contraindications;
• Able to comply with research plans, follow-up plans, and other protocol requirements;
• Voluntary participation and signed informed consent.

You may not qualify if:

• Pathological diagnosis was not pancreatic neuroendocrine tumor, pancreatic ductal adenocarcinoma or solid pseudopapillary tumor;
• Currently diagnosed with other types of tumors or any cancer history;
• Diagnosed with familial syndromes;
• Receiving anti-tumor treatment before surgery, including chemotherapy, embolization, ablation, radiotherapy, and molecular targeted therapy;
• Ongoing fever or recipient of anti-inflammation therapy within 14 days prior to study blood draw;
• Recipient of blood transfusion within 30 days prior to study blood draw;
• Recipient of organ transplant or prior non-autologous (allogeneic) bone marrow or stem cell transplant;
• Poor health condition and not suitable for blood draw;
• Any other disease/condition deemed not suitable for study enrollment by researcher.

Sponsors & Collaborators

• Fudan University: lead
• West China Hospital: collaborator

Study Sites (2)

Fudan University shanghai cancer center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

Related Publications (9)

• Fischer L, Bergmann F, Schimmack S, Hinz U, Priess S, Muller-Stich BP, Werner J, Hackert T, Buchler MW. Outcome of surgery for pancreatic neuroendocrine neoplasms. Br J Surg. 2014 Oct;101(11):1405-12. doi: 10.1002/bjs.9603. Epub 2014 Aug 13.

  PMID: 25132004 BACKGROUND

• 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: 28448665 BACKGROUND

• Zhang X, Wang Z, Tang W, Wang X, Liu R, Bao H, Chen X, Wei Y, Wu S, Bao H, Wu X, Shao Y, Fan J, Zhou J. Ultrasensitive and affordable assay for early detection of primary liver cancer using plasma cell-free DNA fragmentomics. Hepatology. 2022 Aug;76(2):317-329. doi: 10.1002/hep.32308. Epub 2022 Jan 26.

  PMID: 34954829 BACKGROUND

• Fece de la Cruz F, Corcoran RB. Methylation in cell-free DNA for early cancer detection. Ann Oncol. 2018 Jun 1;29(6):1351-1353. doi: 10.1093/annonc/mdy134. No abstract available.

  PMID: 29668834 BACKGROUND

• Mathios D, Johansen JS, Cristiano S, Medina JE, Phallen J, Larsen KR, Bruhm DC, Niknafs N, Ferreira L, Adleff V, Chiao JY, Leal A, Noe M, White JR, Arun AS, Hruban C, Annapragada AV, Jensen SO, Orntoft MW, Madsen AH, Carvalho B, de Wit M, Carey J, Dracopoli NC, Maddala T, Fang KC, Hartman AR, Forde PM, Anagnostou V, Brahmer JR, Fijneman RJA, Nielsen HJ, Meijer GA, Andersen CL, Mellemgaard A, Bojesen SE, Scharpf RB, Velculescu VE. Detection and characterization of lung cancer using cell-free DNA fragmentomes. Nat Commun. 2021 Aug 20;12(1):5060. doi: 10.1038/s41467-021-24994-w.

  PMID: 34417454 BACKGROUND

• Snyder MW, Kircher M, Hill AJ, Daza RM, Shendure J. Cell-free DNA Comprises an In Vivo Nucleosome Footprint that Informs Its Tissues-Of-Origin. Cell. 2016 Jan 14;164(1-2):57-68. doi: 10.1016/j.cell.2015.11.050.

  PMID: 26771485 BACKGROUND

• Guo W, Chen X, Liu R, Liang N, Ma Q, Bao H, Xu X, Wu X, Yang S, Shao Y, Tan F, Xue Q, Gao S, He J. Sensitive detection of stage I lung adenocarcinoma using plasma cell-free DNA breakpoint motif profiling. EBioMedicine. 2022 Jul;81:104131. doi: 10.1016/j.ebiom.2022.104131. Epub 2022 Jun 30.

  PMID: 35780566 BACKGROUND

• Bao H, Wang Z, Ma X, Guo W, Zhang X, Tang W, Chen X, Wang X, Chen Y, Mo S, Liang N, Ma Q, Wu S, Xu X, Chang S, Wei Y, Zhang X, Bao H, Liu R, Yang S, Jiang Y, Wu X, Li Y, Zhang L, Tan F, Xue Q, Liu F, Cai S, Gao S, Peng J, Zhou J, Shao Y. Letter to the Editor: An ultra-sensitive assay using cell-free DNA fragmentomics for multi-cancer early detection. Mol Cancer. 2022 Jun 11;21(1):129. doi: 10.1186/s12943-022-01594-w.

  PMID: 35690859 BACKGROUND

• Ma X, Chen Y, Tang W, Bao H, Mo S, Liu R, Wu S, Bao H, Li Y, Zhang L, Wu X, Cai S, Shao Y, Liu F, Peng J. Multi-dimensional fragmentomic assay for ultrasensitive early detection of colorectal advanced adenoma and adenocarcinoma. J Hematol Oncol. 2021 Oct 26;14(1):175. doi: 10.1186/s13045-021-01189-w.

  PMID: 34702327 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Plasma samples

MeSH Terms

Conditions

Adenoma, Islet Cell

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Xianjun Yu, MD, PhD

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xianjun Yu, MD, PhD

CONTACT

021-64175590-88503; yuxianjun@fudanpci.org

Shunrong Ji, MD, PhD

CONTACT

13788993956; jishunrong@fudanpci.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: President of Shanghai Pancreatic Cancer Institute

Study Record Dates

• First Submitted: April 27, 2023
• First Posted: May 8, 2023
• Study Start: February 27, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: March 25, 2026

Record last verified: 2026-03

Locations

CN (2)