Pancreatic Ductal Adenocarcinoma
Conditions
Keywords
PDAC, Exosome, miRNA, FOLFIRINOX, gemcitabine plus nab-paclitaxel, neoadjuvant chemotherapy
Brief summary
This study aims to develop and validate a predictive microRNA (miRNA) panel to assess the response to neoadjuvant chemotherapy (NACT) in patients with resectable and borderline resectable pancreatic ductal adenocarcinoma (PDAC).
Detailed description
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with a five-year overall survival rate below 12%. Surgical resection combined with systemic chemotherapy offers the best chance for cure; however, only a subset of patients truly benefits from neoadjuvant chemotherapy (NACT). Currently, there are no validated biomarkers to predict response to NACT, making treatment selection largely empirical. The PRECEPT study (PREdiction of Chemotherapy Effect in Pancreatic Cancer Treatment) aims to identify and validate microRNA (miRNA)-based biomarkers from pre-treatment plasma that can predict therapeutic response to neoadjuvant chemotherapy in patients with resectable or borderline resectable PDAC. Specifically, the study focuses on two standard regimens: FOLFIRINOX and gemcitabine plus nab-paclitaxel (GEM-NABP). This is a retrospective, non-interventional, observational study using archived plasma samples collected before the initiation of NACT. Exosomal miRNA sequencing (small RNA-seq) has been performed to identify candidate predictive miRNAs. These candidates will be validated using quantitative reverse transcription PCR (qRT-PCR) in an independent patient cohort. The association between miRNA expression levels and pathologic response (CAP grade or tumor regression score) will be analyzed. Additionally, correlations with overall survival (OS) and recurrence-free survival (RFS) will be explored.
Interventions
DIAGNOSTIC_TESTSmall RNA sequencing
High-throughput small RNA sequencing performed on pre-treatment plasma samples from PDAC patients in the Discovery cohort to identify candidate microRNAs associated with neoadjuvant chemotherapy response. Sequencing data were analyzed to detect differentially expressed miRNAs between responder (CR + PR + SD) and non-responder (PD) groups.
DIAGNOSTIC_TESTPRECEPT assay (qRT-PCR validation)
Quantitative reverse transcription PCR (qRT-PCR)-based validation assay performed on pre-treatment plasma samples in the Training and Validation cohorts. Candidate microRNAs identified in the Discovery cohort by small RNA sequencing were tested using the PRECEPT assay to develop and validate a predictive miRNA panel for neoadjuvant chemotherapy response.
Sponsors
City of Hope Medical Center
Study design
Observational model
CASE_CONTROL
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed pancreatic ductal adenocarcinoma (PDAC). * Underwent neoadjuvant chemotherapy (FOLFIRINOX or Gemcitabine/nab-paclitaxel). * Availability of pre-treatment plasma samples. * Underwent curative-intent resection (R0 or R1).
Exclusion criteria
* Inadequate plasma samples or poor RNA quality for exosomal miRNA analysis. * Non-adenocarcinoma histology. * Presence of synchronous or multiple primary malignancies. * Receipt of chemotherapy regimens other than standard FOLFIRINOX or gemcitabine plus nab-paclitaxel (GEM-NABP). * Presence of active inflammatory or autoimmune diseases.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Response Rate | up to 1 year | Proportion of patients achieving partial or complete pathologic response after neoadjuvant chemotherapy, as assessed using resected pancreatic cancer specimens. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence-Free Survival (RFS) | Up to 3 years after surgery | Time from date of surgical resection to first documented recurrence or death from any cause, whichever occurs first. |
| Overall Survival (OS) | Up to 5 years after surgery | Time from date of surgical resection to date of death from any cause. Patients alive at last follow-up will be censored. |
| Radiologic Response Rate | up to 1 year | Proportion of patients achieving partial or complete radiologic response during neoadjuvant chemotherapy, as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 using contrast-enhanced CT or MRI scans. |
Countries
United States
Contacts
CONTACTAjay Goel, PhD
PRINCIPAL_INVESTIGATORAjay Goel, PhD
City of Hope Medical Center
Outcome results
None listed