Clinical trial NCT05848154: Application of ctDNA in Evaluation of Neoadjuvant Chemotherapy Efficacy and Exploration of Chemoresistance Mechanisms in Pancreatic Cancer
Official title: A Single-center, Observational, Prospective Cohort Study of ctDNA Testing in Evaluation of Neoadjuvant Chemotherapy Efficacy and Exploration of Chemoresistance Mechanisms in Pancreatic Cancer
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Patients With Non-metastatic Pancreatic Cancer
Evaluation of Tumor Resectability Shall be Made in Consensus at Multidisciplinary Meetings, According to NCCN Guideline Version 1.2022 Pancreatic Adenocarcinoma
Keywords: Pancreatic Neoplasms
Circulating tumor DNA
Neoadjuvant Therapy
Treatment Outcome
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
Collaborators: name: Fudan University
name: Amoy Diagnostics
First posted: 2023-05-08
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with non-metastatic pancreatic cancer. Evaluation of tumor resectability should be made in consensus at multidisciplinary meetings/discussions, according to NCCN guideline of pancreatic adenocarcinoma, Version 1.2022.

Brief summary: The purpose of this study is to evaluate the value of ctDNA detection in the assessment of response rate to neoadjuvant chemotherapy in pancreatic cancer and to explore the correlation between ctDNA clearance and prognosis at different time points. Meanwhile, whole exome sequencing (WES) and RNA Sequencing (RNA-seq) of samples of responders and non-responders to neoadjuvant chemotherapy before and after treatment are performed to explore the mechanisms of drug resistance and provide guidance for clinical decision making.

Detailed description: Pancreatic cancer is highly malignant with poor prognosis, and the overall 5-year survival rate is only about 9%. The value of neoadjuvant therapy in pancreatic cancer has been demonstrated by many studies, and a scientific and accurate evaluation of the efficacy of neoadjuvant therapy is crucial to its implementation and achieving the best outcomes. Circulating tumor DNA (ctDNA) analysis provides a non-invasive way to repeatedly assess the genomic profile of tumor. With improvements in detection techniques providing higher levels of sensitivity, ctDNA analysis is rapidly being accepted as a reliable tool in oncology. The purpose of this study is to evaluate the value of ctDNA detection in the assessment of response rate to neoadjuvant chemotherapy in pancreatic cancer and to explore the correlation between ctDNA clearance and prognosis at different time points. Meanwhile, whole exome sequencing (WES) and RNA Sequencing (RNA-seq) of samples of responders and non-responders to neoadjuvant chemotherapy before and after treatment are performed to explore the mechanisms of drug resistance and provide guidance for clinical decision making.

Eligibility criteria: Inclusion Criteria:

* Newly diagnosed patients with non-metastatic pancreatic cancer;
* The pathological features were identified as pancreatic ductal carcinoma;
* Patients with clinical risk factors including significantly elevated CA19-9 levels at diagnosis, large primary tumor volume, large regional lymph node diameter, significant weight loss, and extreme pain;
* Patients accept neoadjuvant chemotherapy voluntarily with the regimen of modified FOLFIRINOX, and disease evaluation should be conducted every two courses, surgery should be performed without delay if resection criteria have been met, and at least two courses of chemotherapy should be completed;
* Age ≥18 years old;
* No other tumor treatment within 4 weeks prior to enrollment;
* Complete clinical data, including basic information, pathological information, treatment information;
* The subjects voluntarily join the study and sign the informed consent with good compliance, and cooperate with the acquisition of tissue samples and regular blood samples.

Exclusion Criteria:

* Any other systemic antitumor therapy priorly;
* Concomitant malignancies under treatment;
* Patients with a history of allergy to relevant chemotherapy agents;
* Failure to comply with the requirements of the visit plan;
* Patients who may be absent from the visit period for 2 weeks or more during the treatment period;
* The researchers determine that the subjects have other factors that could have caused the study to be discontinued.

Primary outcomes:
measure: Objective response rate (ORR) of neoadjuvant therapy in patients with non-metastatic pancreatic cancer
timeFrame: Up to 24 months
Secondary outcomes:
measure: Rate of adverse reactions
timeFrame: One week during therapy and 3 months thereafter up to 24 months.
measure: The correlation between detection of blood ctDNA and mutation characteristics before treatment and the rate of adverse reactions
timeFrame: One week during therapy and 3 months thereafter up to 24 months.
measure: The correlation between postoperative ctDNA in blood and clearance of ctDNA after adjuvant therapy and overall survival (OS) in patients with operable pancreatic cancer
timeFrame: One week during therapy and 3 months thereafter up to 48 months.
measure: The recurrence of pancreatic cancer
timeFrame: One week during therapy and 3 months thereafter up to 24 months.
measure: The timeliness and accuracy of ctDNA with CA19-9 and medical imaging in the detection of disease recurrence
timeFrame: Up to 24 months.
measure: The mechanisms of drug resistance to neoadjuvant chemotherapy
timeFrame: One week during therapy and 3 months thereafter up to 24 months.
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Zhongshan Hospital
state: Shanghai
Study officials:
affiliation: Shanghai Zhongshan Hospital
name: Wen-hui Wen-hui, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Shanghai Zhongshan Hospital
name: Wen-Quan Wang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: