Pancreas Adenocarcinoma (MSI-H)PRODIGE 104 BNCT07592819
A Trial Using Transcriptomic Signatures to Personalize Neoadjuvant Chemotherapy (NAC) for Patients With Resectable Borderline Pancreatic Adenocarcinoma (PDAC)
A study testing mFOLFIRINOX (modified FOLFIRINOX) in people with Pancreas Adenocarcinoma (MSI-H) and Pancreatic Cancer Resectable, run by Institut Paoli-Calmettes.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Pancreas Adenocarcinoma (MSI-H), Pancreatic Cancer Resectable
- What is being tested?
- mFOLFIRINOX (modified FOLFIRINOX)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 367 participants
- Where
- No sites listed yet
- Study dates
- May 2026to Nov 2031
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Borderline-resectable pancreatic ductal adenocarcinoma (BR-PDAC) as defined by the National Comprehensive Cancer Network (NCCN) v2.2025 criteria, identified on contrast-enhanced CT scan and reviewed by a local multidisciplinary pancreatic expert board including at least a medical oncologist / onco-gastroenterologist, a pancreatic surgeon, and an expert pancreatic radiologist. No central review required.
- WHO Performance Status 0-1.
- Histologically confirmed pancreatic ductal adenocarcinoma, including histological variants.
- Patient included-but not randomized-in the PRODIGE 104 A NEOPREDICT study due to a negative gemcitabine sensitivity signature (GEM-).
- Negative gemcitabine transcriptomic signature (test centrally performed in PRODIGE 104 A NEOPREDICT).
- No prior chemotherapy or radiotherapy for pancreatic cancer, and no previous definitive pancreatic cancer resection (except one cycle of mFOLFIRINOX administered while awaiting the signature result).
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- Age > 18 years and < 80 years, with the possibility to include patients aged 75-80 if a standardized geriatric assessment confirms eligibility for the study chemotherapy regimen.
- Ability and willingness to comply with protocol requirements during the entire study period (treatment, scheduled visits, clinical and biological examinations, follow-up).
- Patient's non-opposition to participation in the study.
- Affiliation to the French national health insurance system.
Who cannot join
- Strictly resectable or locally advanced PDAC according to NCCN criteria.
- Distant metastases, including inter-aortocaval lymph nodes.
- Any condition contraindicating the use of irinotecan, oxaliplatin, or 5-FU.
- Complete dihydropyrimidine dehydrogenase (DPD) deficiency.
- Any uncontrolled or unstable medical condition within the past 6 months (e.g., hepatic, renal, respiratory, or cardiac insufficiency).
- Another concomitant malignancy or history of cancer within the past 3 years, except for adequately treated carcinoma in situ of the cervix or basal/squamous cell skin carcinoma.
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- Pregnancy or breastfeeding.
- Patients under legal protection, guardianship, curatorship, or under judicial/administrative protection.
- Patients receiving psychiatric care or unable to provide consent.
- Inability to comply with medical follow-up for geographical, social, or psychological reasons.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Multicenter Randomized Phase II Trial Using Transcriptomic Signatures to Personalize Neoadjuvant Chemotherapy (NAC) for Patients With Resectable Borderline Pancreatic Adenocarcinoma (PDAC)
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
Read the detailed description
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.
- Being tested
- mFOLFIRINOX (modified FOLFIRINOX)
- Keywords
- Transcriptomic-guided chemotherapy, Borderline-resectable pancreatic cancer, Predictive biomarker validation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mFOLFIRINOX (modified FOLFIRINOX)Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| single arm - mFOLFIRINOX | Experimental | Patients GEM- with BR-PDAC receiving standard mFOLFIRINOX according to clinical guidelines. Receives: Drug: mFOLFIRINOX (modified FOLFIRINOX) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From treatment initiation through 1 year
Secondary outcomes (13)
Objective Response Rate (ORR)
Percentage of participants achieving a complete response or partial response per RECIST 1.1 criteria.
Measured: During neoadjuvant chemotherapy (up to 16 weeks)
Overall Survival (OS)
Time from start of treatment to death from any cause.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: At time of surgery
Postoperative Complications (Clavien-Dindo Classification)
Postoperative complications graded from I to V according to Clavien-Dindo.
Measured: Within 60 days after surgery
Time to Recurrence (TTR)
Time from treatment initiation to first recurrence (local or metastatic) or death related to cancer.
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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
Measured: From baseline through study completion (up to 18 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2026
- Study startMay 2026 (estimated)
- Primary completionMay 2030 (estimated)
- Study completionNov 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pancreas Adenocarcinoma (MSI-H)Studies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 367 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institut Paoli-Calmettes
- Sponsor type
- University, hospital or other
- Collaborators
- Federation Francophone de Cancerologie Digestive
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07592819
- Sponsor's protocol ID
- PRODIGE 104 B-NEOPREDICT-IPC 2
- Acronym
- PRODIGE 104 B
- Status last verified
- Apr 2026
- First submitted
- 1 Apr 2026
- Last updated
- 18 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Randomized Phase II Trial Using Transcriptomic Signatures to Personalize Neoadjuvant Chemotherapy (NAC) for Patients With Resectable Borderline Pancreatic Adenocarcinoma (PDAC)
- ClinicalTrials.gov ID
- NCT07592819
- Acronym / sponsor ID
- PRODIGE 104 B / PRODIGE 104 B-NEOPREDICT-IPC 2
- Keywords
- Transcriptomic-guided chemotherapy, Borderline-resectable pancreatic cancer, Predictive biomarker validation
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 367 participants (estimated)
- Lead sponsor
- Institut Paoli-CalmettesUniversity, hospital or other
- Collaborators
- Federation Francophone de Cancerologie Digestive
- Study start
- May 2026 (estimated)
- Primary completion
- May 2030 (estimated)
- Study completion
- Nov 2031 (estimated)
- First posted
- 18 May 2026 (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.
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
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| single arm - mFOLFIRINOX | Experimental | Drug: mFOLFIRINOX (modified FOLFIRINOX)Patients GEM- with BR-PDAC receiving standard mFOLFIRINOX according to clinical guidelines. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Borderline-resectable pancreatic ductal adenocarcinoma (BR-PDAC) as defined by the National Comprehensive Cancer Network (NCCN) v2.2025 criteria, identified on contrast-enhanced CT scan and reviewed by a local multidisciplinary pancreatic expert board including at least a medical oncologist / onco-gastroenterologist, a pancreatic surgeon, and an expert pancreatic radiologist. No central review required.
- WHO Performance Status 0-1.
- Histologically confirmed pancreatic ductal adenocarcinoma, including histological variants.
- Patient included-but not randomized-in the PRODIGE 104 A NEOPREDICT study due to a negative gemcitabine sensitivity signature (GEM-).
- Negative gemcitabine transcriptomic signature (test centrally performed in PRODIGE 104 A NEOPREDICT).
Key exclusion criteria (10 listed)
- Strictly resectable or locally advanced PDAC according to NCCN criteria.
- Distant metastases, including inter-aortocaval lymph nodes.
- Any condition contraindicating the use of irinotecan, oxaliplatin, or 5-FU.
- Complete dihydropyrimidine dehydrogenase (DPD) deficiency.
- Any uncontrolled or unstable medical condition within the past 6 months (e.g., hepatic, renal, respiratory, or cardiac insufficiency).
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 |
|---|---|---|
| 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. | Drug | single arm - mFOLFIRINOX |
Primary outcome
Primary Outcome Measure
Time frame: From treatment initiation through 1 year
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.
13 secondary outcomes
Objective Response Rate (ORR)
Time frame: During neoadjuvant chemotherapy (up to 16 weeks)
Overall Survival (OS)
Time frame: From treatment initiation through study completion (up to 18 months)
Progression-Free Survival (PFS)
Time frame: From treatment initiation through study completion (up to 18 months)
Recurrence-Free Survival (RFS)
Time frame: From treatment initiation through study completion (up to 18 months)
Disease Control Rate (DCR)
Time frame: During neoadjuvant chemotherapy (up to 16 weeks)
Tumor Regression Grade (TRG)
Time frame: At time of surgery
Postoperative Complications (Clavien-Dindo Classification)
Time frame: Within 60 days after surgery
Time to Recurrence (TTR)
Time frame: Up to 18 months
Quality of Life (EORTC QLQ-C30 )
Time frame: From baseline through study completion (up to 18 months)
Completion Rate of Neoadjuvant Chemotherapy (NAC)
Time frame: End of the 4-month NAC period
Adverse Events and Toxicities (NCI-CTCAE v5.0)
Time frame: Before each chemotherapy cycle (Weeks 0-16)
ime to First Deterioration in Global Health Status
Time frame: From treatment initiation through study completion (up to 18 months)
Pancreatic Cancer-Specific Quality of Life (EORTC QLQ-PAN26)
Time frame: From baseline through study completion (up to 18 months)
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 18 May 2026.
- Individual participant dataSharing planned: No
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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.
Questions about this trial
What is this clinical trial studying?
A study testing mFOLFIRINOX (modified FOLFIRINOX) in people with Pancreas Adenocarcinoma (MSI-H) and Pancreatic Cancer Resectable, run by Institut Paoli-Calmettes.
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 10 inclusion and 10 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: opening soon, as of the sponsor's last update on 18 May 2026. Status can change between updates, so confirm with the study contact before making plans.
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?
Contact PAKRADOUNI (+33 4 91 22 37 78, drci.up@ipc.unicancer.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Outcome Measure (time frame: From treatment initiation through 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 May 2026.