Pancreatic Cancer Clinical Trial
— PeRFormanCeOfficial 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
Verified date | January 2024 |
Source | University Hospital, Ghent |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
In this prospective study new diagnostic tools are to be explored for the 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 shall not differ from the gold standard during the study, only extra diagnostic tools will be added and their value is to be analysed post hoc. The 5-year survival rate of pancreatic cancer is 9%, but it can be drastically improved if surgery is possible. With its increasing incidence and dismal prognosis, pancreatic cancer is becoming a global oncologic problem where major breakthroughs are still required to improve outcomes. Patients with BR or LAPDA usually undergo neoadjuvant treatment with FOLFIRINOX chemotherapy, with ulterior referral for surgery in case of response. In these situations, surgical resectability is difficult to predict based on CT because of tumoural desmoplastic reaction, which blurs the tumoural contact with the blood vessels without a clear morphologic change. Consequently, patients without tumoural progression on CT and with a decreased tumour marker (CA 19-9) are considered for surgical exploration, in order not to deny the possibility of a curative path to anyone. However, the unspecific value of CA 19-9 and unreliable spatial changes on CT, do not allow an accurate stratification of the patients. Other diagnostic strategies are necessary for a better prediction of resectability in order to avoid negative laparotomies while not denying a possible curative approach when deemed possible. In this project the investigator will apply diffusion weighted magnetic resonance imaging (DW-MRI) as it has been proven to be useful in the evaluation of tumour response beyond morphologic parameters, with detection of functional tumoural changes, differences in vascularisation or fibrosis without a modification of shape. The statistical evaluation of visual information with radiomics optimises the analysis of data which can be compared in time (before and after chemotherapy) as well as with the operative findings (resectable or unresectable tumour). The investigator will focus on patients with BR and LAPDA and evaluate if a combination of clinical and genetic factors can predict successful surgical resection of tumors. Hereto DW-MRI imaging will be complemented with the evolution of the number of circulating tumour cells (CTC's) in blood samples of patients. Furthermore, the investigator aims to validate in the prospective patient cohort, the predictive value of recently published SNPs (single nucleotide polymorphisms) in genes that regulate cancer progression, invasion, and metastasis and of which some alleles were shown to be associated with an increased risk for tumour-associated death compared with those with protective genotypes.
Status | Recruiting |
Enrollment | 45 |
Est. completion date | March 2026 |
Est. primary completion date | March 2025 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Diagnosis of BR or LA PDAC according to NCCN guidelines 2020 - Preoperative pathologic diagnosis of adenocarcinoma - No medical or anesthetic contra-indication for surgery - Able to understand nature of the study procedures - Willing to participate and give written informed consent Exclusion Criteria: - Distant metastases - Medical or anesthetic contra-indication for surgery - Progression after FOLFIRINOX until 12 cycles in clusters of 4 cycles - Histologic diagnosis of neuroendocrine tumor or duodenal carcinoma - Liver or renal insufficiency - Known hypersensitivity for MRI contrast - Treatment of PDAC with radiotherapy - Pacemaker or prosthesis with incompatibility for MRI - Claustrophobia - Pregnancy or breastfeeding - Not able to understand nature of the study procedure - Performance status ECOG score: 0 -2 - Impossibility to tolerate at least 4 cycles FOLFIRINOX |
Country | Name | City | State |
---|---|---|---|
Belgium | Ghent University Hospital | Ghent | East Flanders |
Belgium | University Hospital Ghent | Ghent |
Lead Sponsor | Collaborator |
---|---|
University Hospital, Ghent |
Belgium,
Bobek 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. — View Citation
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. — View Citation
Gemenetzis 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. — View Citation
Harouaka 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. — View Citation
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. — View Citation
Kolostova 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. — View Citation
Marchegiani 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. — View Citation
Okubo 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. Erratum In: Eur J Surg Oncol. 2018 Mar 28;: — View Citation
Poruk 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. — View Citation
Poruk 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. — View Citation
Rebelo et al. Circulating tumor cells in pancreatic cancer: a review. Journal of pancreatology (2019) 2:2.
Sollier 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. — View Citation
Tang 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. — View Citation
* Note: There are 13 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Prediciton 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). | 2 years | |
Secondary | 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). | 2 years | |
Secondary | Perioperative complications | Evaluation according to Clavien-Dindo classification | 2 years | |
Secondary | Generic measurement of health status | Questionnaire EQ-5D-5L | 4 years | |
Secondary | Overall survival | 4 years | ||
Secondary | Disease free survival | 4 years | ||
Secondary | Measurement of quality of life in patients with pancreatic cancer | Questionnaire PAN 26 | 4 years |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT05305001 -
Germline Mutations Associated With Hereditary Pancreatic Cancer in Unselected Patients With Pancreatic Cancer in Mexico
|
||
Completed |
NCT02526017 -
Study of Cabiralizumab in Combination With Nivolumab in Patients With Selected Advanced Cancers
|
Phase 1 | |
Recruiting |
NCT05497531 -
Pilot Comparing ctDNA IDV vs. SPV Sample in Pts Undergoing Biopsies for Hepatobiliary and Pancreatic Cancers
|
N/A | |
Recruiting |
NCT06054984 -
TCR-T Cells in the Treatment of Advanced Pancreatic Cancer
|
Early Phase 1 | |
Recruiting |
NCT04927780 -
Perioperative or Adjuvant mFOLFIRINOX for Resectable Pancreatic Cancer
|
Phase 3 | |
Recruiting |
NCT05919537 -
Study of an Anti-HER3 Antibody, HMBD-001, With or Without Chemotherapy in Patients With Solid Tumors Harboring an NRG1 Fusion or HER3 Mutation
|
Phase 1 | |
Terminated |
NCT03140670 -
Maintenance Rucaparib in BRCA1, BRCA2 or PALB2 Mutated Pancreatic Cancer That Has Not Progressed on Platinum-based Therapy
|
Phase 2 | |
Terminated |
NCT00529113 -
Study With Gemcitabine and RTA 402 for Patients With Unresectable Pancreatic Cancer
|
Phase 1 | |
Recruiting |
NCT05168527 -
The First Line Treatment of Fruquintinib Combined With Albumin Paclitaxel and Gemcitabine in Pancreatic Cancer Patients
|
Phase 2 | |
Active, not recruiting |
NCT04383210 -
Study of Seribantumab in Adult Patients With NRG1 Gene Fusion Positive Advanced Solid Tumors
|
Phase 2 | |
Recruiting |
NCT05391126 -
GENOCARE: A Prospective, Randomized Clinical Trial of Genotype-Guided Dosing Versus Usual Care
|
N/A | |
Terminated |
NCT03300921 -
A Phase Ib Pharmacodynamic Study of Neoadjuvant Paricalcitol in Resectable Pancreatic Cancer A Phase Ib Pharmacodynamic Study of Neoadjuvant Paricalcitol in Resectable Pancreatic Cancer
|
Phase 1 | |
Completed |
NCT03153410 -
Pilot Study With CY, Pembrolizumab, GVAX, and IMC-CS4 (LY3022855) in Patients With Borderline Resectable Adenocarcinoma of the Pancreas
|
Early Phase 1 | |
Recruiting |
NCT03175224 -
APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors
|
Phase 2 | |
Recruiting |
NCT05679583 -
Preoperative Stereotactic Body Radiation Therapy in Patients With Resectable Pancreatic Cancer
|
Phase 2 | |
Recruiting |
NCT04183478 -
The Efficacy and Safety of K-001 in the Treatment of Advanced Pancreatic Cancer
|
Phase 2/Phase 3 | |
Terminated |
NCT03600623 -
Folfirinox or Gemcitabine-Nab Paclitaxel Followed by Stereotactic Body Radiotherapy for Locally Advanced Pancreatic Cancer
|
Early Phase 1 | |
Recruiting |
NCT04584008 -
Targeted Agent Evaluation in Digestive Cancers in China Based on Molecular Characteristics
|
N/A | |
Recruiting |
NCT05351983 -
Patient-derived Organoids Drug Screen in Pancreatic Cancer
|
N/A | |
Completed |
NCT04290364 -
Early Palliative Care in Pancreatic Cancer - a Quasi-experimental Study
|