Prediction of Neoadjuvant Chemotherapy Response in Pancreatic Cancer (PRECEPT)

City of Hope

Status: Enrolling

Conditions: Pancreatic Ductal Adenocarcinoma

Treatments: Diagnostic Test: PRECEPT assay (qRT-PCR validation); Diagnostic Test: Small RNA sequencing

Study type: Observational

Funder types: Other

Identifiers

NCT07226154

19288/PRECEPT

Details and patient eligibility

About

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).

Full 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.

Enrollment: 200 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

200 participants in 6 patient groups

Discovery Cohort - NAC Responder Group

Description:

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.

Treatment:

Diagnostic Test: Small RNA sequencing

Discovery Cohort - NAC Non-Responder Group

Description:

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.

Treatment:

Diagnostic Test: Small RNA sequencing

Training Cohort - NAC Responder Group

Description:

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.

Treatment:

Diagnostic Test: PRECEPT assay (qRT-PCR validation)

Training Cohort - NAC Non-Responder Group

Description:

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.

Treatment:

Diagnostic Test: PRECEPT assay (qRT-PCR validation)

Validation Cohort - NAC Responder Group

Description:

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.

Treatment:

Diagnostic Test: PRECEPT assay (qRT-PCR validation)

Validation Cohort - NAC Non-Responder Group

Description:

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.

Treatment:

Diagnostic Test: PRECEPT assay (qRT-PCR validation)