Pancreatic CancerPeRFormanCeNCT05298722
Prediction of Surgical Resectability After FOLFIRINOX Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: the Role of Diffusion Weighted Magnetic Resonance Imaging, Radiomics and Liquid Biopsy (PeRFormanCe Trial)
A study testing Imaging analysis of CT-scan and MRI with radiomics and genetic analysis of peripheral blood samples and questionnaires. in people with Pancreatic Cancer, run by University Hospital, Ghent at 8 sites in 2 countries.
Trial summary
In this prospective study, new diagnostic tools will be explored for patients with borderline resectable and locally advanced pancreatic ductal adenocarcinoma (BR or LAPDA) who undergo neoadjuvant chemotherapy with FOLFIRINOX. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Pancreatic Cancer
- What is being tested?
- Imaging analysis of CT-scan and MRI with radiomics and genetic analysis of peripheral blood samples and questionnaires.
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 8 sitesin 2 countries
- Study dates
- 12 Dec 2022to Mar 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male or female patients, aged 18 years and above
- Diagnosis of BR or LA PDAC according to NCCN guidelines (version 1.2020)
- Histologic diagnosis of PDAC
- No medical or anesthetic contra-indication for surgery
- Able to understand nature of the study procedures
- Willing to participate and give written informed consent
Who cannot join
- Age < 18 years
- Distant metastases
- Histologic diagnosis of cholangiocarcinoma, duodenal carcinoma or neuroendocrine tumor
- Known hypersensitivity for MRI contrast
- Pacemaker or prosthesis with incompatibility for MRI
- Claustrophobia
Show all 9Show fewer
- Pregnancy or breastfeeding
- Not able to understand nature of the study procedure
- Performance status ECOG score: >2
Trial locations and contacts
8 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
8 sites in 2 countries
Belgium7 sites, 7 recruiting
- Recruiting
AZ Sint Blasius Dendermonde
Dendermonde, 9200
Lars Triest, MD, +32 5 225 2011, Lars.Triest@azsintblasius.be
- Recruiting
AZ Alma Eeklo
Eeklo, 9900
Barbara Claerhout, MD, +32 9 310 0000, Barbara.Claerhout@azalma.be
- Recruiting
Ghent University Hospital
Ghent, East Flanders, 9000
Luis Filipe Abreu de Carvalho, MD, +32 9 332 5519, luis.abreudecarvalho@uzgent.be
betsy Van Loo, nurse, +32 9 332 4183, HBSurgeryStudy@uzgent.be
- Recruiting
AZ Jan Palfijn Ghent
Ghent, 9000
Steven Sas, MD, +32 9 224 7111, steven.sas@skynet.be
- Recruiting
AZ Sint Lucs Ghent
Ghent, 9000
Johan Van Ongeval, MD, +32 9 224 6480, johan.vanongeval@azstlucas.be
- Recruiting
AZ Oudenaarde
Oudenaarde, 9700
Carolien Beyls, MD, +32 5 533 6111, Carolien.Beyls@azoudenaarde.be
- Recruiting
AZ Vitaz Sint Niklaas - Lokeren
Sint-Niklaas, 9100
Willem Lybaert, MD, +32 3 7606060, willem.lybaert@telenet.be
Koen Gorleer, MD
Netherlands1 site, 1 recruiting
- Recruiting
ZorgSaam ZH DeHonte Terneuzen
Terneuzen, Zeeland, 4535 PA
Mark Sie, M.D. Ph.D. M.Sc., +31 115 688 000, m.sie@zzv.nl
Marjan van Dijk, MD
About this study
Official title: Prediction of Surgical Resectability After FOLFIRINOX Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: the Role of Diffusion Weighted Magnetic Resonance Imaging, Radiomics and Liquid Biopsy
In this prospective study, new diagnostic tools will be explored for patients with borderline resectable and locally advanced pancreatic ductal adenocarcinoma (BR or LAPDA) who undergo neoadjuvant chemotherapy with FOLFIRINOX. The diagnostic work-up and therapy for the study population will not differ from the gold standard during the study; only additional diagnostic tools will be implemented, and their value will be analyzed post hoc.
The 5-year survival rate of pancreatic cancer is 9%, but this can be drastically improved if surgery is possible. With its increasing incidence and poor prognosis, pancreatic cancer is becoming a global oncologic challenge where major breakthroughs are still required to improve patient outcomes. Patients with BR or LAPDA typically undergo neoadjuvant treatment with FOLFIRINOX chemotherapy, followed by referral for surgery if a response is observed. In these cases, surgical resectability is difficult to predict based on CT imaging due to the tumor's desmoplastic reaction, which obscures tumor-vessel contact without clear morphological changes. Consequently, patients without tumor progression on CT and with a decreased tumor marker (CA 19-9) are considered for surgical exploration to ensure that no potentially curative treatment is denied. However, the non-specific nature of CA 19-9 and the unreliable spatial changes on CT do not allow for accurate patient stratification. Therefore, alternative diagnostic strategies are needed to better predict resectability, minimizing unnecessary laparotomies while ensuring that potentially curative approaches are not overlooked.
Read more
In this project, the investigator will apply diffusion-weighted magnetic resonance imaging (DW-MRI), as it has been shown to be useful in assessing tumor response beyond morphological parameters. DW-MRI enables the detection of functional tumor changes, variations in vascularization, and fibrosis without modifications in shape. The statistical evaluation of visual information using radiomics optimizes data analysis, allowing comparisons over time (before and after chemotherapy) and correlation with operative findings (resectable or unresectable tumor).
The investigator will focus on patients with BR and LAPDA and assess whether a combination of clinical and genetic factors can predict successful surgical resection. To this end, DW-MRI imaging will be complemented by multi-omics profiling in liquid biopsies. Furthermore, the investigator aims to validate, in a prospective patient cohort, the predictive value of recently published single nucleotide polymorphisms (SNPs) in genes that regulate cancer progression, invasion, and metastasis. Some alleles of these SNPs have been associated with an increased risk of tumor-related mortality compared to protective genotypes.
Read the detailed description
Study Aim The aim of this study is to assess whether the combination of radiomics, diffusion-weighted magnetic resonance imaging (DW-MRI), and multi-omics profiling in liquid biopsies-both before and after neoadjuvant chemotherapy-can predict the probability of achieving successful surgical excision in patients with borderline resectable (BR) and locally advanced pancreatic ductal adenocarcinoma (LAPDA).
Additionally, a subgroup analysis will be performed, taking into account risk alleles of single nucleotide polymorphisms (SNPs) that have recently been associated with worse survival outcomes.
The primary endpoint of this study is to improve the prediction of surgical resectability following neoadjuvant chemotherapy with FOLFIRINOX in patients with BR and LAPDA. The focus is on increasing diagnostic specificity to better identify patients with unresectable tumors, thereby avoiding unnecessary exploratory laparotomies that may delay further chemotherapy.
Secondary endpoints include the evaluation of postoperative complications, cost minimization, and disease-free and overall survival.
Background \& Rationale All factors evaluated in this study-DW-MRI, radiomics, genetic markers (SNPs), and multi-omics profiling in liquid biopsies-have individually shown promise for early diagnosis, prognosis assessment, and correlation with tumor response to chemotherapy in pancreatic cancer. However, these modalities have never been combined in an innovative study such as this, where they are integrated to enhance clinical decision-making.
This project aims to apply existing knowledge to have an immediate impact on therapeutic decision-making, reducing unnecessary surgical explorations and ultimately improving patient quality of life while optimizing treatment efficiency.
Patients with BR or LAPDA typically undergo neoadjuvant treatment with FOLFIRINOX, followed by referral for surgery if they respond to chemotherapy. However, surgical resectability is challenging to predict using CT imaging alone, as the tumor's desmoplastic reaction can obscure tumor-vessel contact without clear morphological changes. As a result, patients with stable disease on CT and a decreased CA 19-9 level are considered for surgical exploration to ensure that no potentially curative treatment is withheld.
Since CA 19-9 is non-specific and CT lacks reliable spatial resolution for detecting subtle tumor changes, alternative strategies are needed to improve resectability predictions and avoid negative laparotomies. DW-MRI has demonstrated its value in evaluating tumor response beyond morphological parameters, while radiomics can enhance data analysis. Additionally, multi-omics profiling using liquid biopsies has shown a correlation with tumor response to chemotherapy in pancreatic cancer, though its utility in the neoadjuvant setting remains unclear.
Objective This multicenter prospective study aims to assess the utility of DW-MRI, radiomics, and liquid biopsy in predicting tumor resectability after neoadjuvant treatment with FOLFIRINOX in patients with BR and LAPDA.
When chemotherapy results in a reduction of CA 19-9 but no significant morphological change on CT, some tumors may still be eligible for an R0 resection. The investigator hypothesizes that these cases can be preoperatively identified by detecting a reduction in multi-omics markers in liquid biopsies, along with decreased vascularity and cellularity in the tumor-vessel interface on DW-MRI.
Study Design A prospective interventional study with a single study arm.
Study Population Patients with BR or LAPDA scheduled for neoadjuvant chemotherapy with FOLFIRINOX and without contraindications for pancreatic surgery.
A minimum sample size of 45 patients undergoing surgical exploration has been calculated (80% power, α = 0.05, two-tailed).
Intervention Patients with BR and LAPDA will be discussed in a multidisciplinary oncologic meeting and will receive standard-of-care treatment. In addition to routine clinical evaluation, CT imaging, and CA 19-9 assessment before and after chemotherapy, participants will undergo DW-MRI and provide a peripheral blood sample for multi-omics profiling in liquid biopsies.
If no tumor progression is observed on imaging and CA 19-9 levels decrease post-chemotherapy, patients will be considered for surgical exploration. During surgery, a blood sample will be collected from the supra-pancreatic portal vein to measure circulating tumor cells (CTCs) before and after tumor resection-if an R0 resection is feasible.
Additionally, a peripheral blood sample will be taken at the first postoperative consultation to analyze multi-omics profiling in liquid biopsies and CA 19-9 levels.
Burden, Risks, and Benefits of Participation Compared to standard care, participants in this study will undergo two additional DW-MRI scans and provide extra peripheral blood samples.
DW-MRI is a widely used, safe imaging modality, and blood samples are routinely collected as part of oncologic treatment. The study aims to refine surgical decision-making, minimizing unnecessary procedures and ultimately improving patient outcomes.
- Conditions
- Pancreatic Cancer
- Being tested
- Imaging analysis of CT-scan and MRI with radiomics and genetic analysis of peripheral blood samples and questionnaires.
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Imaging analysis of CT-scan and MRI with radiomics and genetic analysis of peripheral blood samples and questionnaires.Diagnostic test
Also called Analysis of imaging with radiomics and genetic analysis of peripheral blood samples (liquid biopsy)
- The images from CT scans and MRI with DWI will be processed using specialized software to determine the direction of diffusion tensors. This will indicate the diffusion direction using color coding (red, green, and blue for the x, y, and z components of the vector) and the intensity using anisotropy (brightness of voxels). Further analysis will be performed using fiber tracking, which provides a clear representation of the functional connectivity of adjacent tissues.
- Genetic profiling of liquid biopsies: Multi-omics profiling of liquid biopsies (blood samples) will be conducted, followed by cell phenotyping, longitudinal analysis of driver mutations and epigenetic changes in cfDNA, and genotyping of germline variations.
- Questionnaires for patient-reported outcomes and health economic analysis:
EQ-5D-5L PAN 26 HADS
| Study group | Role | What they receive |
|---|---|---|
| Study arm | Other | Imaging with CT-scan and MRI-DWI and peripheral blood samples for liquid biopsy Receives: Diagnostic Test: Imaging analysis of CT-scan and MRI with radiomics and genetic analysis of peripheral blood samples and questionnaires. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prediction of surgical resectability
Create an algorithm to predict surgical resectability of BR and LA PDAC after neoadjuvant FOLFIRINOX with radiomics analysis of CT and DW-MRI to determine the tumoral vascular invasion in combination with the evolution of CA19-9 and genetic profilling of liquid biopsies (phenotyping and quantification of the CTCs, longitudinal analysis of driver mutations and epigenetic changes in cfDNA).
Measured: 2 years
R1 resection rate
Measured: 2 years
Histopathological response
Measured: 2 years
Secondary outcomes (6)
Prediction of R0 resection
Create an algorithm to predict R0 surgical resectability of BR and LA PDAC after neoadjuvant FOLFIRINOX with radiomics analysis of CT and DW-MRI to determine the tumoral vascular invasion in combination with the evolution of CA19-9 and genetic profilling of liquid biopsies (phenotyping and quantification of the CTCs, longitudinal analysis of driver mutations and epigenetic changes in cfDNA).
Measured: 2 years
Perioperative complications
Evaluation according to Clavien-Dindo classification
Measured: 2 years
Generic measurement of health status
Questionnaire EQ-5D-5L
Measured: 4 years
Overall survival
Measured: 4 years
Disease free survival
Measured: 4 years
Measurement of quality of life in patients with pancreatic cancer
Questionnaire PAN 26
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2022
- Study start12 Dec 2022
- Primary completionMar 2026 (estimated)
- Study completionMar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Pancreatic CancerStudies of the same condition, open and under way.
- More trials run by University Hospital, GhentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Ghent
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05298722
- Sponsor's protocol ID
- ONZ-2022-0088 - PeRFormanCe
- Acronym
- PeRFormanCe
- Status last verified
- Sep 2024
- First submitted
- 22 Nov 2021
- Last updated
- 2 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: If a multicentric study should arise in the future to combine data of this subpopuplation of patients with pancreatic cancer, it would be interesting to analyze a larger studypopulation in order to possibly achieve more signicant conclusions.
Publications
Isaji S, Mizuno S, Windsor JA, Bassi C, Fernandez-Del Castillo C, Hackert T, Hayasaki A, Katz MHG, Kim SW, Kishiwada M, Kitagawa H, Michalski CW, Wolfgang CL. International consensus on definition and criteria of borderline resectable pancreatic ductal adenocarcinoma 2017. Pancreatology. 2018 Jan;18(1):2-11. doi: 10.1016/j.pan.2017.11.011. Epub 2017 Nov 22.
PubMed 29191513Marchegiani G, Todaro V, Boninsegna E, Negrelli R, Sureka B, Bonamini D, Salvia R, Manfredi R, Pozzi Mucelli R, Bassi C. Surgery after FOLFIRINOX treatment for locally advanced and borderline resectable pancreatic cancer: increase in tumour attenuation on CT correlates with R0 resection. Eur Radiol. 2018 Oct;28(10):4265-4273. doi: 10.1007/s00330-018-5410-6. Epub 2018 Apr 20.
PubMed 29679211Gemenetzis G, Groot VP, Yu J, Ding D, Teinor JA, Javed AA, Wood LD, Burkhart RA, Cameron JL, Makary MA, Weiss MJ, He J, Wolfgang CL. Circulating Tumor Cells Dynamics in Pancreatic Adenocarcinoma Correlate With Disease Status: Results of the Prospective CLUSTER Study. Ann Surg. 2018 Sep;268(3):408-420. doi: 10.1097/SLA.0000000000002925.
PubMed 30080739Tang L, Zhou XJ. Diffusion MRI of cancer: From low to high b-values. J Magn Reson Imaging. 2019 Jan;49(1):23-40. doi: 10.1002/jmri.26293. Epub 2018 Oct 12.
PubMed 30311988Rebelo et al. Circulating tumor cells in pancreatic cancer: a review. Journal of pancreatology (2019) 2:2.
Dimitrakopoulos C, Vrugt B, Flury R, Schraml P, Knippschild U, Wild P, Hoerstrup S, Henne-Bruns D, Wuerl P, Graf R, Breitenstein S, Bond G, Beerenwinkel N, Grochola LF. Identification and Validation of a Biomarker Signature in Patients With Resectable Pancreatic Cancer via Genome-Wide Screening for Functional Genetic Variants. JAMA Surg. 2019 Jun 1;154(6):e190484. doi: 10.1001/jamasurg.2019.0484. Epub 2019 Jun 19.
PubMed 30942874Okubo K, Uenosono Y, Arigami T, Mataki Y, Matsushita D, Yanagita S, Kurahara H, Sakoda M, Kijima Y, Maemura K, Natsugoe S. Clinical impact of circulating tumor cells and therapy response in pancreatic cancer. Eur J Surg Oncol. 2017 Jun;43(6):1050-1055. doi: 10.1016/j.ejso.2017.01.241. Epub 2017 Feb 12.
PubMed 28233633Poruk KE, Valero V 3rd, Saunders T, Blackford AL, Griffin JF, Poling J, Hruban RH, Anders RA, Herman J, Zheng L, Rasheed ZA, Laheru DA, Ahuja N, Weiss MJ, Cameron JL, Goggins M, Iacobuzio-Donahue CA, Wood LD, Wolfgang CL. Circulating Tumor Cell Phenotype Predicts Recurrence and Survival in Pancreatic Adenocarcinoma. Ann Surg. 2016 Dec;264(6):1073-1081. doi: 10.1097/SLA.0000000000001600.
PubMed 26756760Poruk KE, Blackford AL, Weiss MJ, Cameron JL, He J, Goggins M, Rasheed ZA, Wolfgang CL, Wood LD. Circulating Tumor Cells Expressing Markers of Tumor-Initiating Cells Predict Poor Survival and Cancer Recurrence in Patients with Pancreatic Ductal Adenocarcinoma. Clin Cancer Res. 2017 Jun 1;23(11):2681-2690. doi: 10.1158/1078-0432.CCR-16-1467. Epub 2016 Oct 27.
PubMed 27789528Harouaka RA, Nisic M, Zheng SY. Circulating tumor cell enrichment based on physical properties. J Lab Autom. 2013 Dec;18(6):455-68. doi: 10.1177/2211068213494391. Epub 2013 Jul 5.
PubMed 23832928Sollier E, Go DE, Che J, Gossett DR, O'Byrne S, Weaver WM, Kummer N, Rettig M, Goldman J, Nickols N, McCloskey S, Kulkarni RP, Di Carlo D. Size-selective collection of circulating tumor cells using Vortex technology. Lab Chip. 2014 Jan 7;14(1):63-77. doi: 10.1039/c3lc50689d. Epub 2013 Sep 23.
PubMed 24061411Kolostova K, Rzechonek A, Schutzner J, Grill R, Lischke R, Hladik P, Simonek J, Bobek V. Circulating Tumor Cells as an Auxiliary Diagnostic Tool in Surgery. In Vivo. 2017 Nov-Dec;31(6):1197-1202. doi: 10.21873/invivo.11190.
PubMed 29102946Bobek V, Gurlich R, Eliasova P, Kolostova K. Circulating tumor cells in pancreatic cancer patients: enrichment and cultivation. World J Gastroenterol. 2014 Dec 7;20(45):17163-70. doi: 10.3748/wjg.v20.i45.17163.
PubMed 25493031de Carvalho LFA, Ceelen W, Meertens A, Rashidian N, Waked B, Geboes K, Ribeiro S, Gorleer K, Dedecker H, Triest L, Vervaecke A, Sas S, Sierens B, Beyls C, Sie M, van Dijk M, Verhaeghe N, Berrevoet F. Longitudinal assessment of health-related quality of life in patients with borderline and locally advanced pancreatic cancer undergoing neoadjuvant FOLFIRINOX chemotherapy: results from a prospective multicenter trial. Langenbecks Arch Surg. 2026 Jul 1. doi: 10.1007/s00423-026-04121-3. Online ahead of print.
PubMed 42384236Abreu de Carvalho LF, Gryspeerdt F, Ceelen W, Geboes K, Ribeiro S, Hoorens A, Vandenbussche N, Claes KBM, Lecluyse C, Anisau A, Van Ongeval J, Lybaert W, Triest L, Vervaecke A, Sas S, Claerhout B, Beyls C, Sie M, Berrevoet F. Prediction of surgical resectability after FOLFIRINOX chemotherapy for borderline resectable and locally advanced pancreatic cancer (PeRFormanCe): a multicenter prospective trial - trial protocol. BMC Surg. 2025 May 13;25(1):204. doi: 10.1186/s12893-025-02938-1.
PubMed 40361171
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prediction of Surgical Resectability After FOLFIRINOX Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: the Role of Diffusion Weighted Magnetic Resonance Imaging, Radiomics and Liquid Biopsy
- ClinicalTrials.gov ID
- NCT05298722
- Acronym / sponsor ID
- PeRFormanCe / ONZ-2022-0088 - PeRFormanCe
- Conditions
- Pancreatic Cancer
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- University Hospital, GhentUniversity, hospital or other
- Study start
- 12 Dec 2022 (actual)
- Primary completion
- Mar 2026 (estimated)
- Study completion
- Mar 2028 (estimated)
- First posted
- 28 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this prospective study, new diagnostic tools will be explored for patients with borderline resectable and locally advanced pancreatic ductal adenocarcinoma (BR or LAPDA) who undergo neoadjuvant chemotherapy with FOLFIRINOX. The diagnostic work-up and therapy for the study population will not differ from the gold standard during the study; only additional diagnostic tools will be implemented, and their value will be analyzed post hoc.
The 5-year survival rate of pancreatic cancer is 9%, but this can be drastically improved if surgery is possible. With its increasing incidence and poor prognosis, pancreatic cancer is becoming a global oncologic challenge where major breakthroughs are still required to improve patient outcomes. Patients with BR or LAPDA typically undergo neoadjuvant treatment with FOLFIRINOX chemotherapy, followed by referral for surgery if a response is observed. In these cases, surgical resectability is difficult to predict based on CT imaging due to the tumor's desmoplastic reaction, which obscures tumor-vessel contact without clear morphological changes. Consequently, patients without tumor progression on CT and with a decreased tumor marker (CA 19-9) are considered for surgical exploration to ensure that no potentially curative treatment is denied. However, the non-specific nature of CA 19-9 and the unreliable spatial changes on CT do not allow for accurate patient stratification. Therefore, alternative diagnostic strategies are needed to better predict resectability, minimizing unnecessary laparotomies while ensuring that potentially curative approaches are not overlooked.
In this project, the investigator will apply diffusion-weighted magnetic resonance imaging (DW-MRI), as it has been shown to be useful in assessing tumor response beyond morphological parameters. DW-MRI enables the detection of functional tumor changes, variations in vascularization, and fibrosis without modifications in shape. The statistical evaluation of visual information using radiomics optimizes data analysis, allowing comparisons over time (before and after chemotherapy) and correlation with operative findings (resectable or unresectable tumor).
The investigator will focus on patients with BR and LAPDA and assess whether a combination of clinical and genetic factors can predict successful surgical resection. To this end, DW-MRI imaging will be complemented by multi-omics profiling in liquid biopsies. Furthermore, the investigator aims to validate, in a prospective patient cohort, the predictive value of recently published single nucleotide polymorphisms (SNPs) in genes that regulate cancer progression, invasion, and metastasis. Some alleles of these SNPs have been associated with an increased risk of tumor-related mortality compared to protective genotypes.
Detailed description
Study Aim The aim of this study is to assess whether the combination of radiomics, diffusion-weighted magnetic resonance imaging (DW-MRI), and multi-omics profiling in liquid biopsies-both before and after neoadjuvant chemotherapy-can predict the probability of achieving successful surgical excision in patients with borderline resectable (BR) and locally advanced pancreatic ductal adenocarcinoma (LAPDA).
Additionally, a subgroup analysis will be performed, taking into account risk alleles of single nucleotide polymorphisms (SNPs) that have recently been associated with worse survival outcomes.
The primary endpoint of this study is to improve the prediction of surgical resectability following neoadjuvant chemotherapy with FOLFIRINOX in patients with BR and LAPDA. The focus is on increasing diagnostic specificity to better identify patients with unresectable tumors, thereby avoiding unnecessary exploratory laparotomies that may delay further chemotherapy.
Secondary endpoints include the evaluation of postoperative complications, cost minimization, and disease-free and overall survival.
Background \& Rationale All factors evaluated in this study-DW-MRI, radiomics, genetic markers (SNPs), and multi-omics profiling in liquid biopsies-have individually shown promise for early diagnosis, prognosis assessment, and correlation with tumor response to chemotherapy in pancreatic cancer. However, these modalities have never been combined in an innovative study such as this, where they are integrated to enhance clinical decision-making.
This project aims to apply existing knowledge to have an immediate impact on therapeutic decision-making, reducing unnecessary surgical explorations and ultimately improving patient quality of life while optimizing treatment efficiency.
Patients with BR or LAPDA typically undergo neoadjuvant treatment with FOLFIRINOX, followed by referral for surgery if they respond to chemotherapy. However, surgical resectability is challenging to predict using CT imaging alone, as the tumor's desmoplastic reaction can obscure tumor-vessel contact without clear morphological changes. As a result, patients with stable disease on CT and a decreased CA 19-9 level are considered for surgical exploration to ensure that no potentially curative treatment is withheld.
Since CA 19-9 is non-specific and CT lacks reliable spatial resolution for detecting subtle tumor changes, alternative strategies are needed to improve resectability predictions and avoid negative laparotomies. DW-MRI has demonstrated its value in evaluating tumor response beyond morphological parameters, while radiomics can enhance data analysis. Additionally, multi-omics profiling using liquid biopsies has shown a correlation with tumor response to chemotherapy in pancreatic cancer, though its utility in the neoadjuvant setting remains unclear.
Objective This multicenter prospective study aims to assess the utility of DW-MRI, radiomics, and liquid biopsy in predicting tumor resectability after neoadjuvant treatment with FOLFIRINOX in patients with BR and LAPDA.
When chemotherapy results in a reduction of CA 19-9 but no significant morphological change on CT, some tumors may still be eligible for an R0 resection. The investigator hypothesizes that these cases can be preoperatively identified by detecting a reduction in multi-omics markers in liquid biopsies, along with decreased vascularity and cellularity in the tumor-vessel interface on DW-MRI.
Study Design A prospective interventional study with a single study arm.
Study Population Patients with BR or LAPDA scheduled for neoadjuvant chemotherapy with FOLFIRINOX and without contraindications for pancreatic surgery.
A minimum sample size of 45 patients undergoing surgical exploration has been calculated (80% power, α = 0.05, two-tailed).
Intervention Patients with BR and LAPDA will be discussed in a multidisciplinary oncologic meeting and will receive standard-of-care treatment. In addition to routine clinical evaluation, CT imaging, and CA 19-9 assessment before and after chemotherapy, participants will undergo DW-MRI and provide a peripheral blood sample for multi-omics profiling in liquid biopsies.
If no tumor progression is observed on imaging and CA 19-9 levels decrease post-chemotherapy, patients will be considered for surgical exploration. During surgery, a blood sample will be collected from the supra-pancreatic portal vein to measure circulating tumor cells (CTCs) before and after tumor resection-if an R0 resection is feasible.
Additionally, a peripheral blood sample will be taken at the first postoperative consultation to analyze multi-omics profiling in liquid biopsies and CA 19-9 levels.
Burden, Risks, and Benefits of Participation Compared to standard care, participants in this study will undergo two additional DW-MRI scans and provide extra peripheral blood samples.
DW-MRI is a widely used, safe imaging modality, and blood samples are routinely collected as part of oncologic treatment. The study aims to refine surgical decision-making, minimizing unnecessary procedures and ultimately improving patient outcomes.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Study arm | Other | Diagnostic Test: Imaging analysis of CT-scan and MRI with radiomics and genetic analysis of peripheral blood samples and questionnaires.Imaging with CT-scan and MRI-DWI and peripheral blood samples for liquid biopsy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female patients, aged 18 years and above
- Diagnosis of BR or LA PDAC according to NCCN guidelines (version 1.2020)
- Histologic diagnosis of PDAC
- No medical or anesthetic contra-indication for surgery
- Able to understand nature of the study procedures
Key exclusion criteria (9 listed)
- Age < 18 years
- Distant metastases
- Histologic diagnosis of cholangiocarcinoma, duodenal carcinoma or neuroendocrine tumor
- Known hypersensitivity for MRI contrast
- Pacemaker or prosthesis with incompatibility for MRI
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Imaging analysis of CT-scan and MRI with radiomics and genetic analysis of peripheral blood samples and questionnaires.Also: Analysis of imaging with radiomics and genetic analysis of peripheral blood samples (liquid biopsy)* The images from CT scans and MRI with DWI will be processed using specialized software to determine the direction of diffusion tensors. This will indicate the diffusion direction using color coding (red, green, and blue for the x, y, and z components of the vector) and the intensity using anisotropy (brightness of voxels). Further analysis will be performed using fiber tracking, which provides a clear representation of the functional connectivity of adjacent tissues. * Genetic profiling of liquid biopsies: Multi-omics profiling of liquid biopsies (blood samples) will be conducted, followed by cell phenotyping, longitudinal analysis of driver mutations and epigenetic changes in cfDNA, and genotyping of germline variations. * Questionnaires for patient-reported outcomes and health economic analysis: EQ-5D-5L PAN 26 HADS | Diagnostic test | Study arm |
Primary outcome
Prediction of surgical resectability
Time frame: 2 years
Create an algorithm to predict surgical resectability of BR and LA PDAC after neoadjuvant FOLFIRINOX with radiomics analysis of CT and DW-MRI to determine the tumoral vascular invasion in combination with the evolution of CA19-9 and genetic profilling of liquid biopsies (phenotyping and quantification of the CTCs, longitudinal analysis of driver mutations and epigenetic changes in cfDNA).
R1 resection rate
Time frame: 2 years
Histopathological response
Time frame: 2 years
6 secondary outcomes
Prediction of R0 resection
Time frame: 2 years
Perioperative complications
Time frame: 2 years
Generic measurement of health status
Time frame: 4 years
Overall survival
Time frame: 4 years
Disease free survival
Time frame: 4 years
Measurement of quality of life in patients with pancreatic cancer
Time frame: 4 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2025.
- Background: PubMed 29191513Isaji S, Mizuno S, Windsor JA, Bassi C, Fernandez-Del Castillo C, Hackert T, Hayasaki A, Katz MHG, Kim SW, Kishiwada M, Kitagawa H, Michalski CW, Wolfgang CL. International consensus on definition and criteria of borderline resectable pancreatic ductal adenocarcinoma 2017. Pancreatology. 2018 Jan;18(1):2-11. doi: 10.1016/j.pan.2017.11.011. Epub 2017 Nov 22.
- Background: PubMed 29679211Marchegiani G, Todaro V, Boninsegna E, Negrelli R, Sureka B, Bonamini D, Salvia R, Manfredi R, Pozzi Mucelli R, Bassi C. Surgery after FOLFIRINOX treatment for locally advanced and borderline resectable pancreatic cancer: increase in tumour attenuation on CT correlates with R0 resection. Eur Radiol. 2018 Oct;28(10):4265-4273. doi: 10.1007/s00330-018-5410-6. Epub 2018 Apr 20.
- Background: PubMed 30080739Gemenetzis G, Groot VP, Yu J, Ding D, Teinor JA, Javed AA, Wood LD, Burkhart RA, Cameron JL, Makary MA, Weiss MJ, He J, Wolfgang CL. Circulating Tumor Cells Dynamics in Pancreatic Adenocarcinoma Correlate With Disease Status: Results of the Prospective CLUSTER Study. Ann Surg. 2018 Sep;268(3):408-420. doi: 10.1097/SLA.0000000000002925.
- Background: PubMed 30311988Tang L, Zhou XJ. Diffusion MRI of cancer: From low to high b-values. J Magn Reson Imaging. 2019 Jan;49(1):23-40. doi: 10.1002/jmri.26293. Epub 2018 Oct 12.
- BackgroundRebelo et al. Circulating tumor cells in pancreatic cancer: a review. Journal of pancreatology (2019) 2:2.
- Background: PubMed 30942874Dimitrakopoulos C, Vrugt B, Flury R, Schraml P, Knippschild U, Wild P, Hoerstrup S, Henne-Bruns D, Wuerl P, Graf R, Breitenstein S, Bond G, Beerenwinkel N, Grochola LF. Identification and Validation of a Biomarker Signature in Patients With Resectable Pancreatic Cancer via Genome-Wide Screening for Functional Genetic Variants. JAMA Surg. 2019 Jun 1;154(6):e190484. doi: 10.1001/jamasurg.2019.0484. Epub 2019 Jun 19.
- Background: PubMed 28233633Okubo K, Uenosono Y, Arigami T, Mataki Y, Matsushita D, Yanagita S, Kurahara H, Sakoda M, Kijima Y, Maemura K, Natsugoe S. Clinical impact of circulating tumor cells and therapy response in pancreatic cancer. Eur J Surg Oncol. 2017 Jun;43(6):1050-1055. doi: 10.1016/j.ejso.2017.01.241. Epub 2017 Feb 12.
- Background: PubMed 26756760Poruk KE, Valero V 3rd, Saunders T, Blackford AL, Griffin JF, Poling J, Hruban RH, Anders RA, Herman J, Zheng L, Rasheed ZA, Laheru DA, Ahuja N, Weiss MJ, Cameron JL, Goggins M, Iacobuzio-Donahue CA, Wood LD, Wolfgang CL. Circulating Tumor Cell Phenotype Predicts Recurrence and Survival in Pancreatic Adenocarcinoma. Ann Surg. 2016 Dec;264(6):1073-1081. doi: 10.1097/SLA.0000000000001600.
- Background: PubMed 27789528Poruk KE, Blackford AL, Weiss MJ, Cameron JL, He J, Goggins M, Rasheed ZA, Wolfgang CL, Wood LD. Circulating Tumor Cells Expressing Markers of Tumor-Initiating Cells Predict Poor Survival and Cancer Recurrence in Patients with Pancreatic Ductal Adenocarcinoma. Clin Cancer Res. 2017 Jun 1;23(11):2681-2690. doi: 10.1158/1078-0432.CCR-16-1467. Epub 2016 Oct 27.
- Background: PubMed 23832928Harouaka RA, Nisic M, Zheng SY. Circulating tumor cell enrichment based on physical properties. J Lab Autom. 2013 Dec;18(6):455-68. doi: 10.1177/2211068213494391. Epub 2013 Jul 5.
- Background: PubMed 24061411Sollier E, Go DE, Che J, Gossett DR, O'Byrne S, Weaver WM, Kummer N, Rettig M, Goldman J, Nickols N, McCloskey S, Kulkarni RP, Di Carlo D. Size-selective collection of circulating tumor cells using Vortex technology. Lab Chip. 2014 Jan 7;14(1):63-77. doi: 10.1039/c3lc50689d. Epub 2013 Sep 23.
- Background: PubMed 29102946Kolostova K, Rzechonek A, Schutzner J, Grill R, Lischke R, Hladik P, Simonek J, Bobek V. Circulating Tumor Cells as an Auxiliary Diagnostic Tool in Surgery. In Vivo. 2017 Nov-Dec;31(6):1197-1202. doi: 10.21873/invivo.11190.
- Individual participant dataSharing planned: Undecided. If a multicentric study should arise in the future to combine data of this subpopuplation of patients with pancreatic cancer, it would be interesting to analyze a larger studypopulation in order to possibly achieve more signicant conclusions.
Related trials for Pancreatic Cancer
Enrolling by invitationPhase 2
A Single-Arm Study of Nimotuzumab Combined With NALIRIFOX as First-Line Treatment for Pancreatic Cancer
Pancreatic Cancer Metastatic
RecruitingPhase 2/3
Multicenter Validation Trial of [18F]AlF-FAPI-74 for PET Imaging of Cancer-associated Fibroblasts Through Fibroblast Activation Protein Inhibitors (FAPI) in Different Tumor Types
Oesophageal Cancer, Gastric Cancer
RecruitingPhase 1
Modified FOLFIRINOX and Pentamidine in Advanced and Metastatic Pancreatic Cancer
Pancreatic Ductal Adenocarcinoma (PDAC)
RecruitingPhase 3
Atebimetinib + GnP as a First Line Treatment in Patients With Metastatic Pancreatic Adenocarcinoma
Pancreatic Cancer, Pancreatic Cancer Metastatic
RecruitingPhase 3
Lanreotide Versus Placebo Before Surgery to Prevent a Surgical Complication Called a Pancreatic Fistula
Pancreatic Carcinoma, Pancreatic Neoplasm
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Imaging analysis of CT-scan and MRI with radiomics and genetic analysis of peripheral blood samples and questionnaires. in people with Pancreatic Cancer, run by University Hospital, Ghent at 8 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Belgium, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prediction of surgical resectability (time frame: 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05298722, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2025.