Prediction of Neoadjuvant Chemotherapy Response in Pancreatic Cancer

NCT07226154 | Recruiting

• 1 other identifier: 19288/PRECEPT
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

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).

Conditions

Pancreatic Ductal Adenocarcinoma

Keywords

PDAC; Exosome; miRNA; FOLFIRINOX; gemcitabine plus nab-paclitaxel; neoadjuvant chemotherapy

Outcome Measures

Primary Outcomes (1)

• Pathological Response Rate

  Proportion of patients achieving partial or complete pathologic response after neoadjuvant chemotherapy, as assessed using resected pancreatic cancer specimens.

  up to 1 year

Secondary Outcomes (3)

• Recurrence-Free Survival (RFS)

  Up to 3 years after surgery

• Overall Survival (OS)

  Up to 5 years after surgery

• Radiologic Response Rate

  up to 1 year

Study Arms (6)

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

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

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)

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)

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)

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)

Interventions

Small RNA sequencing 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 Non-Responder Group; Discovery Cohort - NAC Responder Group

PRECEPT assay (qRT-PCR validation) 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; Training Cohort - NAC Responder Group; Validation Cohort - NAC Non-Responder Group; Validation Cohort - NAC Responder Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC) who received neoadjuvant chemotherapy (FOLFIRINOX or Gemcitabine + Nab-paclitaxel) followed by surgery.

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• City of Hope Medical Center: lead

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91016, United States

RECRUITING

Related Publications (11)

• Mannucci A, Goel A. Advances in pancreatic cancer early diagnosis, prevention, and treatment: The past, the present, and the future. CA Cancer J Clin. 2026 Jan-Feb;76(1):e70035. doi: 10.3322/caac.70035. Epub 2025 Sep 19.

  PMID: 40971231 BACKGROUND

• 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.

  PMID: 37798442 BACKGROUND

• 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.

  PMID: 41024179 BACKGROUND

• 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.

  PMID: 35785193 BACKGROUND

• 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.

  PMID: 21652542 BACKGROUND

• Philip PA, Lacy J, Portales F, Sobrero A, Pazo-Cid R, Manzano Mozo JL, Kim EJ, Dowden S, Zakari A, Borg C, Terrebonne E, Rivera F, Sastre J, Bathini V, Lopez-Trabada D, Asselah J, Saif MW, Shiansong Li J, Ong TJ, Nydam T, Hammel P. Nab-paclitaxel plus gemcitabine in patients with locally advanced pancreatic cancer (LAPACT): a multicentre, open-label phase 2 study. Lancet Gastroenterol Hepatol. 2020 Mar;5(3):285-294. doi: 10.1016/S2468-1253(19)30327-9. Epub 2020 Jan 14.

  PMID: 31953079 BACKGROUND

• 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.

  PMID: 33338442 BACKGROUND

• 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.

  PMID: 38237621 BACKGROUND

• 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.

  PMID: 39310355 BACKGROUND

• 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.

  PMID: 38315795 BACKGROUND

• 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.

  PMID: 36932224 BACKGROUND

Study Officials

• Ajay Goel, PhD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ajay Goel, PhD

CONTACT

626-218-3452; ajgoel@coh.org

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2025
• First Posted: November 10, 2025
• Study Start: November 15, 2024
• Primary Completion (Estimated): June 18, 2026
• Study Completion (Estimated): June 18, 2026
• Last Updated: November 21, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)