Clinical trial NCT06151691: Assessment of Early Pancreatic Cancer Prognosis by Minimal Residual Disease Using Multi-omics Approach
Official title: 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
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Pancreatic Ductal Adenocarcinoma
Lead sponsor: Fudan University
Sponsor class: OTHER
Collaborators: name: Shanghai Weihe Medical Laboratory Co., Ltd.
First posted: 2023-11-30
Enrollment: 51
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 1.5-year disease-free survival
timeFrame: 18 months
Secondary outcomes:
measure: Sensitivity of the multi-omics prognostic model
timeFrame: 18 months
measure: Specificity of the multi-omics prognostic model
timeFrame: 18 months
measure: Area under the receiver operating characteristic curve (AUROC) of the multi-omics prognostic model
timeFrame: 18 months
measure: Sensitivity of the multi-omics prognostic model in different subgroups
timeFrame: 18 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center; Pancreatic Cancer Institute, Fudan University; 270 Dong An Road, Shanghai 200032, China
Study officials:
References: