Prediction of Neoadjuvant Chemotherapy Response in Pancreatic Cancer

NCT ID: NCT07226154

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

200 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-11-15

Study Completion Date

2026-06-18

Brief Summary

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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

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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.

Conditions

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Pancreatic Ductal Adenocarcinoma

Keywords

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PDAC Exosome miRNA FOLFIRINOX gemcitabine plus nab-paclitaxel neoadjuvant chemotherapy

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

RETROSPECTIVE

Study Groups

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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.

PRECEPT assay (qRT-PCR validation)

Intervention Type DIAGNOSTIC_TEST

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.

PRECEPT assay (qRT-PCR validation)

Intervention Type DIAGNOSTIC_TEST

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.

PRECEPT assay (qRT-PCR validation)

Intervention Type DIAGNOSTIC_TEST

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.

PRECEPT assay (qRT-PCR validation)

Intervention Type DIAGNOSTIC_TEST

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.

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.

Small RNA sequencing

Intervention Type DIAGNOSTIC_TEST

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 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.

Small RNA sequencing

Intervention Type DIAGNOSTIC_TEST

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.

Interventions

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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.

Intervention Type 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.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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City of Hope Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ajay Goel, PhD

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Locations

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City of Hope Medical Center

Duarte, California, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Ajay Goel, PhD

Role: CONTACT

Phone: 626-218-3452

Email: [email protected]

Facility Contacts

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Ajay Goel, PhD

Role: primary

References

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Mannucci A, Goel A. Advances in pancreatic cancer early diagnosis, prevention, and treatment: The past, the present, and the future. CA Cancer J Clin. 2025 Sep 19. doi: 10.3322/caac.70035. Online ahead of print.

Reference Type BACKGROUND
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Hu ZI, O'Reilly EM. Therapeutic developments in pancreatic cancer. Nat Rev Gastroenterol Hepatol. 2024 Jan;21(1):7-24. doi: 10.1038/s41575-023-00840-w. Epub 2023 Oct 5.

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Sha M, Gao Y, Yin X, Li X, Liu C, Li S. Engineered exosomes: a promising approach for overcoming challenges in pancreatic cancer therapy. J Nanobiotechnology. 2025 Sep 29;23(1):619. doi: 10.1186/s12951-025-03697-0.

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Wang C, Tan G, Zhang J, Fan B, Chen Y, Chen D, Yang L, Chen X, Duan Q, Maimaiti F, Du J, Lin Z, Gu J, Luo H. Neoadjuvant Therapy for Pancreatic Ductal Adenocarcinoma: Where Do We Go? Front Oncol. 2022 Jun 16;12:828223. doi: 10.3389/fonc.2022.828223. eCollection 2022.

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Preis M, Gardner TB, Gordon SR, Pipas JM, Mackenzie TA, Klein EE, Longnecker DS, Gutmann EJ, Sempere LF, Korc M. MicroRNA-10b expression correlates with response to neoadjuvant therapy and survival in pancreatic ductal adenocarcinoma. Clin Cancer Res. 2011 Sep 1;17(17):5812-21. doi: 10.1158/1078-0432.CCR-11-0695. Epub 2011 Jun 7.

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Kunzmann V, Siveke JT, Algul H, Goekkurt E, Siegler G, Martens U, Waldschmidt D, Pelzer U, Fuchs M, Kullmann F, Boeck S, Ettrich TJ, Held S, Keller R, Klein I, Germer CT, Stein H, Friess H, Bahra M, Jakobs R, Hartlapp I, Heinemann V; German Pancreatic Cancer Working Group (AIO-PAK) and NEOLAP investigators. Nab-paclitaxel plus gemcitabine versus nab-paclitaxel plus gemcitabine followed by FOLFIRINOX induction chemotherapy in locally advanced pancreatic cancer (NEOLAP-AIO-PAK-0113): a multicentre, randomised, phase 2 trial. Lancet Gastroenterol Hepatol. 2021 Feb;6(2):128-138. doi: 10.1016/S2468-1253(20)30330-7. Epub 2020 Dec 16.

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Labori KJ, Bratlie SO, Andersson B, Angelsen JH, Biorserud C, Bjornsson B, Bringeland EA, Elander N, Garresori H, Gronbech JE, Haux J, Hemmingsson O, Liljefors MG, Myklebust TA, Nymo LS, Peltola K, Pfeiffer P, Sallinen V, Sandstrom P, Sparrelid E, Stenvold H, Soreide K, Tingstedt B, Verbeke C, Ohlund D, Klint L, Dueland S, Lassen K; Nordic Pancreatic Cancer Trial-1 study group. Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1): a multicentre, randomised, phase 2 trial. Lancet Gastroenterol Hepatol. 2024 Mar;9(3):205-217. doi: 10.1016/S2468-1253(23)00405-3. Epub 2024 Jan 15.

Reference Type BACKGROUND
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Yeung KTD, Kumar S, Cunningham D, Jiao LR, Bhogal RH. Surgical Outcomes Following Neoadjuvant Treatment for Locally Advanced and Borderline Resectable Pancreatic Ductal Adenocarcinoma. Ann Surg Open. 2024 Sep 4;5(3):e486. doi: 10.1097/AS9.0000000000000486. eCollection 2024 Sep.

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Leonhardt CS, Hank T, Pils D, Gustorff C, Sahora K, Schindl M, Verbeke CS, Strobel O, Klaiber U. Prognostic impact of resection margin status on survival after neoadjuvant treatment for pancreatic cancer: systematic review and meta-analysis. Int J Surg. 2024 Jan 1;110(1):453-463. doi: 10.1097/JS9.0000000000000792.

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Springfeld C, Ferrone CR, Katz MHG, Philip PA, Hong TS, Hackert T, Buchler MW, Neoptolemos J. Neoadjuvant therapy for pancreatic cancer. Nat Rev Clin Oncol. 2023 May;20(5):318-337. doi: 10.1038/s41571-023-00746-1. Epub 2023 Mar 17.

Reference Type BACKGROUND
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Other Identifiers

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19288/PRECEPT

Identifier Type: -

Identifier Source: org_study_id