Assessment of Early Pancreatic Cancer Prognosis by Minimal Residual Disease Using Multi-omics Approach

Explorations of Cell-free DNA Multi-omics Technology in Detection of Minimal Residual Disease and Disease Prognosis After Surgery in Early Pancreatic Ductal Adenocarcinoma: A Single-center, Prospective, Observational Case Study

This trial aims to develop a minimal residual disease (MRD) detection model for predicting recurrence of patients with stage I-II pancreatic ductal adenocarcinoma after surgery and adjuvant therapy, based on cfDNA fragmentation and methylation signal.

Study Overview

• Status: Not yet recruiting
• Conditions: Pancreatic Ductal Adenocarcinoma
• Intervention / Treatment: Other: Blood collection and Pancreatic ductal adenocarcinoma minimal residual disease detection test

Detailed Description

The entire study is divided into two stages. Stage one is the enrollment period. 51 subjects with pancreatic ductal adenocarcinoma in stages I-II who have not received neoadjuvant therapy and have undergone radical surgery were enrolled. Blood samples at the time point before surgical treatment (T0) were collected and fresh tissue specimens (cancerous tissue and adjacent normal tissue) were collected. Blood samples were subjected to methylation, fragment group, and CNV multi-omics testing, and tissue samples were subjected to target methylation area testing. Stage two is the follow-up period. Blood samples from the fifth week after surgery to before adjuvant therapy (T1) and blood samples from 4-8 weeks after adjuvant therapy (T2) were collected. Blood samples were subjected to methylation, fragment group, and CNV multi-omics testing with different techniques. The subjects were followed up for 1.5 years. According to progression and recurrence, the subjects were divided into progression group and non-progression group. Methylation and multi-omics prognosis models were trained and compared for their performance in residual detection and recurrence prediction.

• Study Type: Observational
• Enrollment (Estimated): 51

Contacts and Locations

• Study Contact: Name: Xian-Jun Yu, M.D., Ph.D.; Phone Number: +86 21 64175590; Email: yuxianjun@fudanpci.org
• Study Contact Backup: Name: Si Shi, M.D., Ph.D.; Phone Number: +86 21 64175590

Study Locations

• China
  • Shanghai, China, 200032
    • Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center; Pancreatic Cancer Institute, Fudan University; 270 Dong An Road, Shanghai 200032, China

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Eligible participants will be recruited from clinic and medical centers. Participants are defined as new diagnosis cancer patients with pancreatic ductal adenocarcinoma. Demographic and cancer risk-related characteristics (eg, age, gender, smoking status, diabetes) will be collected from all enrolled subjects.

Description

Inclusion criteria:

1. Patients with clinically and/or pathologically diagnosis of stage I/II pancreatic ductal adenocarcinoma;
2. Aged ≥ 40 years and < 75 years, both sexes;
3. Patients receive radical resection with curative intent, followed by adjuvant therapy;
4. Tumour size not less than 1 cm * 1 cm * 1 cm and be able to provide surgical tissue samples for molecular testing after pathological evaluation;
5. Eastern Cooperative Oncology Group (ECOG) score of 0-2;
6. Negative margins (R0 or R1) by naked eye or no recurrence/metastasis detected on imaging after surgery or before adjuvant therapy, and CA 19-9<37 U/ml;
7. Patients understand and voluntarily sign the informed consent form and follow the sampling, assessment and visit requirements of this study.

Exclusion criteria:

1. Pregnant and lactating (by self-report);
2. Any tumor history of malignancies;
3. Positive cutting margins (R2);
4. Received neoadjuvant therapy before surgery;
5. Not be able to receive radical surgery;
6. Organ transplantation history;
7. Organ dysfunction (moderate or severe renal impairment with absolute centrocyte count < 1.0 x 10^9/L, platelet count < 75 x 10^9/L, haemoglobin < 80 g/L, AST/ALT > 2.5 times upper limit of normal);
8. Other conditions deemed unsuitable for enrollment by the investigator.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Case-Cancer arm; Blood collection and Pancreatic ductal adenocarcinoma minimal residual disease detection test	Other: Blood collection and Pancreatic ductal adenocarcinoma minimal residual disease detection test; Blood samples of participants meet the inclusion/exclusion criteria will be collected. Pancreatic ductal adenocarcinoma minimal residual disease detection test.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1.5-year disease-free survival	1.5-year disease-free survival of patients with pancreatic ductal adenocarcinoma receiving post-operative adjuvant chemotherapy.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity of the multi-omics prognostic model	Sensitivity of the multi-omics prognostic model for pancreatic ductal adenocarcinoma based on cfDNA methylation, fragmentation group, and CNV features in patients with recurrence at 95% confidence interval	18 months
Specificity of the multi-omics prognostic model	Specificity of the multi-omics prognostic model for pancreatic ductal adenocarcinoma patients without recurrence at 95% confidence intervals.	18 months
Area under the receiver operating characteristic curve (AUROC) of the multi-omics prognostic model	Area under the receiver operating characteristic curve (AUROC) of the multi-omics prognostic model for predicting patient recurrence of pancreatic ductal adenocarcinoma at 95% confidence intervals.	18 months
Sensitivity of the multi-omics prognostic model in different subgroups	Sensitivity of the multi-omics prognostic model for predicting pancreatic ductal adenocarcinoma recurrence in different subgroups (age, underlying medical history, tumour differentiation, tumour diameter, etc.) at 95% confidence intervals.	18 months

Collaborators and Investigators

• Sponsor: Fudan University
• Collaborators: Shanghai Weihe Medical Laboratory Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2023
• Primary Completion (Estimated): September 30, 2025
• Study Completion (Estimated): November 30, 2025

Study Registration Dates

• First Submitted: November 22, 2023
• First Submitted That Met QC Criteria: November 29, 2023
• First Posted (Actual): November 30, 2023

Study Record Updates

• Last Update Posted (Actual): November 30, 2023
• Last Update Submitted That Met QC Criteria: November 29, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplastic Processes; Adenocarcinoma; Neoplasm, Residual
• Other Study ID Numbers: PC-MRD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No