An interventional study of mFOLFIRINOX (modified FOLFIRINOX) in Pancreas Adenocarcinoma (MSI-H) and Pancreatic Cancer Resectable, sponsored by Institut Paoli-Calmettes. Not yet recruiting. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-05-18.
Sponsored by Institut Paoli-Calmettes · Not applicable, Interventional, and Treatment
Pancreatic cancer exhibits significant heterogeneity, which poses a major challenge in selecting the best treatment for patients from the very beginning of care. Modern oncology recognizes the use of companion biomarkers to guide targeted therapy or immune checkpoint inhibitors. However, with regard to chemotherapy-which has long been the cornerstone of cancer treatment and remains crucial for most cancers-few predictive tests are available to guide the choice between monotherapy and combination chemotherapy.
Patients included in the PRODIGE 104 B - NEOPREDICT study will be those for whom the GEM transcriptomic signature is negative. This population will be treated according to the standard strategy and will be followed clinically and biologically to describe and identify the characteristics specific to this subgroup, and to compare the usual prognostic factors of this population with those of the GEM-positive population included in the parallel PRODIGE 104 A - NEOPREDICT study
Transcriptomic Signature for Patient Stratification and Prediction of Chemotherapy Sensitivity Transcriptomic signatures, derived from RNA-sequencing, capture unique patterns of gene expression that reflect the molecular phenotype of a tumor and can indicate its potential sensitivity or resistance to chemotherapeutic agents. Over the past decade, several molecular classifications of PDAC have been established (Collisson, Moffitt, Bailey), consistently distinguishing two major tumor subtypes: basal-like (poor prognosis) and classical (better prognosis). While these classifications provide strong prognostic information, they have not reliably predicted chemotherapy response in clinical practice.
Recent advances from the Dusetti/Iovanna research group have led to the development of robust transcriptomic signatures capable of predicting sensitivity to gemcitabine, irinotecan, 5-FU, oxaliplatin, and paclitaxel. These signatures-collectively referred to as Pancreas-View-were generated using preclinical models (PDX, organoids, primary cultures) and have been clinically validated, notably the gemcitabine-sensitivity signature in two retrospective cohorts and in the prospective PRODIGE 24 trial. Importantly, these signatures can be performed on FFPE-derived RNA with minimal material and rapid turnaround, making them compatible with real-world decision-making in the neoadjuvant setting.
Position of the Study Within Current Knowledge Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal disease due to late diagnosis, limited actionable biomarkers, and the modest efficacy of targeted and immunotherapeutic approaches. Its incidence is rising in Western countries, and without improved strategies, PDAC is projected to become the second leading cause of cancer-related death by 2040.
Borderline-resectable PDAC accounts for approximately 20% of cases and typically requires complex multidisciplinary management. Neoadjuvant chemotherapy (NAC)-now an international standard in BR-PDAC-offers several advantages: improved R0 resection rates, treatment of occult micrometastatic disease, and avoidance of futile surgery in rapidly progressing tumors.
Two main NAC regimens are currently used: mFOLFIRINOX and Gemcitabine + Nab-Paclitaxel. However, comparative studies in non-metastatic PDAC have not demonstrated a clear superiority of one regimen over the other, though their toxicity profiles differ substantially. As a result, selecting the optimal chemotherapy strategy remains challenging.
There is therefore a strong need for predictive biomarkers capable of guiding neoadjuvant regimen selection. The NEOPREDICT program positions itself directly within this unmet clinical need, evaluating the use of a transcriptomic gemcitabine-sensitivity signature to personalize treatment.
Exclusion Criteria:
Patients GEM- with BR-PDAC receiving standard mFOLFIRINOX according to clinical guidelines.
Drug: mFOLFIRINOX (modified FOLFIRINOX)
Patients with borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) who are negative for the gemcitabine sensitivity transcriptomic signature (GEM-) receive neoadjuvant mFOLFIRINOX chemotherapy as standard of care. This observational cohort follows patients prospectively without modifying routine management.
Primary Outcome Measure
Event-Free Survival is defined as the time from the start of treatment to the occurrence of any of the following events: * disease progression, * failure to undergo pancreatic resection, * death from any cause, * grade IV febrile neutropenia or grade IV diarrhea occurring during neoadjuvant chemotherapy. Participants without an event will be censored at the date of last follow-up.
Time frame: From treatment initiation through 1 year
Objective Response Rate (ORR)
Percentage of participants achieving a complete response or partial response per RECIST 1.1 criteria.
Time frame: During neoadjuvant chemotherapy (up to 16 weeks)
Overall Survival (OS)
Time from start of treatment to death from any cause.
Time frame: From treatment initiation through study completion (up to 18 months)
Progression-Free Survival (PFS)
For non-operated patients: time from treatment initiation to disease progression or death from any cause.
Time frame: From treatment initiation through study completion (up to 18 months)
Recurrence-Free Survival (RFS)
For operated patients: time from treatment initiation to first local or metastatic recurrence or death.
Time frame: From treatment initiation through study completion (up to 18 months)
Disease Control Rate (DCR)
Percentage of patients achieving complete response, partial response, or stable disease.
Time frame: During neoadjuvant chemotherapy (up to 16 weeks)
Tumor Regression Grade (TRG)
Pathologic tumor response assessed using Ryan's simplified Tumor Regression Grade (TRG 1-3) on the resected primary tumor.
Time frame: At time of surgery
Postoperative Complications (Clavien-Dindo Classification)
Postoperative complications graded from I to V according to Clavien-Dindo.
Time frame: Within 60 days after surgery
Time to Recurrence (TTR)
Time from treatment initiation to first recurrence (local or metastatic) or death related to cancer.
Time frame: Up to 18 months
Quality of Life (EORTC QLQ-C30 )
Change over time in the Global Health Status/Quality of Life scale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30).
Time frame: From baseline through study completion (up to 18 months)
Completion Rate of Neoadjuvant Chemotherapy (NAC)
Percentage of participants who completed all 8 cycles of mFOLFIRINOX (regardless of dose modifications).
Time frame: End of the 4-month NAC period
Adverse Events and Toxicities (NCI-CTCAE v5.0)
Incidence and severity of treatment-related toxicities graded according to NCI-CTCAE v5.0.
Time frame: Before each chemotherapy cycle (Weeks 0-16)
ime to First Deterioration in Global Health Status
Time to first deterioration of more than 5 points from baseline in the EORTC QLQ-C30 global health status score.
Time frame: From treatment initiation through study completion (up to 18 months)
Pancreatic Cancer-Specific Quality of Life (EORTC QLQ-PAN26)
Change over time in symptom and functional scores assessed using the EORTC QLQ-PAN26 pancreatic
Time frame: From baseline through study completion (up to 18 months)
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Plan to share: No
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