Prediction of Neoadjuvant Chemotherapy Response in Pancreatic Cancer

Purpose

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).

Condition

  • Pancreatic Ductal Adenocarcinoma

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts 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.

Study Design

Phase
Study Type
Observational
Observational Model
Case-Control
Time Perspective
Retrospective

Arm Groups

ArmDescriptionAssigned Intervention
Discovery Cohort - NAC Responder Group Patients with resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC) who received neoadjuvant chemotherapy (FOLFIRINOX or gemcitabine plus nab-paclitaxel) and achieved a clinical or pathological response. Responders were defined as patients showing complete response (CR), partial response (PR), or stable disease (SD) according to radiologic or pathologic assessment after NACT. Pre-treatment plasma samples from these patients were analyzed by small RNA sequencing to identify microRNAs associated with favorable chemotherapy response.
  • Diagnostic Test: Small 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.
Discovery Cohort - NAC Non-Responder Group Patients with resectable or borderline resectable PDAC who received neoadjuvant chemotherapy but demonstrated progressive disease (PD) on radiologic or pathologic evaluation. Pre-treatment plasma samples from these patients were analyzed in parallel by small RNA sequencing to identify differential miRNA expression compared with responders.
  • Diagnostic Test: Small 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.
Training Cohort - NAC Responder Group PDAC patients treated with neoadjuvant chemotherapy (FOLFIRINOX or gemcitabine plus nab-paclitaxel) who achieved CR, PR, or SD responses. Candidate microRNAs identified in the Discovery cohort were validated using qRT-PCR (PRECEPT assay). Responder group data were used to train and optimize the predictive miRNA panel.
  • Diagnostic Test: PRECEPT 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.
Training Cohort - NAC Non-Responder Group PDAC patients who received neoadjuvant chemotherapy but exhibited progressive disease (PD). Plasma miRNA expression was measured using the PRECEPT assay and compared with responders to refine the predictive model for chemotherapy response.
  • Diagnostic Test: PRECEPT 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.
Validation Cohort - NAC Responder Group A separate validation cohort of PDAC patients treated with neoadjuvant chemotherapy who achieved CR, PR, or SD. The established PRECEPT miRNA panel (qRT-PCR) was applied to evaluate predictive accuracy in this independent responder group.
  • Diagnostic Test: PRECEPT 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.
Validation Cohort - NAC Non-Responder Group Independent PDAC patients who received neoadjuvant chemotherapy and demonstrated progressive disease (PD). This cohort was used to confirm the predictive performance and robustness of the PRECEPT miRNA assay compared with responders.
  • Diagnostic Test: PRECEPT 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.

Recruiting Locations

City of Hope Medical Center
Duarte, California 91016
Contact:
Ajay Goel, PhD
626-218-3452
ajgoel@coh.org

More Details

Status
Recruiting
Sponsor
City of Hope Medical Center

Study Contact

Ajay Goel, PhD
626-218-3452
ajgoel@coh.org

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.