PRODIGE 104 – NEOPREDICT A multicenter phase II trial using transcriptomic signatures to personalize neoadjuvant chemotherapy for patients with resectable borderline pancreatic adenocarcinoma.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondation Franc.Cancerologie Digestive

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Decision date (initial)

2025-10-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate the efficacy of treating patients with borderline resectable pancreatic ductal adenocarcinoma (BR PDAC) identified with a Gemcitabine positive sensitivity transcriptomic signature (GEM +) with GEMCITABINE + NAB-PACLITAXEL regimen compared to standard of care mFOLFIRINOX as NeoAdjuvant Chemotherapy (NAC) on event-free survival (EFS) at 1 year

Secondary objectives 13

1. Objectif Response Rate (ORR)
2. Pathology Tumor Regression Grade (TRG) according to the simplified Ryan TRG on the primary tumor after surgery
3. Post-operative complications according to Clavien-Dindo
4. Resection rate
5. Resection parameters: ypTNM and margin (R0-R1)
6. Toxicities of neoadjuvant chemotherapy
7. Overall Survival (OS)
8. Progression-Free Survival (PFS) for patients without surgery
9. Disease Free Survival (DFS) for patients with surgery
10. Time To Recurrence (TTR) for patients with surgery
11. Quality of life (QLQ)
12. Percentage of neoadjuvant chemotherapy completion
13. Proportion of adjuvant chemotherapy (begin/completion)

Conditions and MedDRA coding

Resectable borderline pancreatic adenocarcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) defined by National Comprehensive Cancer Network (NCCN) criteria v2.2025 on contrast-enhanced CT-scan, with stage confirmed by a local pancreatic expert review board including at least medical oncologist/onco-gastroenterologist, pancreatic surgeon and pancreatic expert radiologist. No central review is required
2. Adequate organ function, as defined by the following: o AST and ALT < 3.5 x upper limit of normal (ULN), o Total serum bilirubin < 3 x ULN, (for patients with total serum bilirubin between 1.5 and 3 x ULN, the dose of irinotecan will be adjusted in accordance with the SmPC). o Serum albumin >30 g/L, o Hemoglobin >9.0 g/dl, o Absolute neutrophil count (ANC) >1.5 G/L, o Platelets >100 G/L, o Creatinine clearance > 50 mL/min (according to CKD-EPI)
3. Measurable pancreatic lesion according to RECIST 1.1 (CT scan or MRI < 28 days),
4. WHO PS 1 or 0
5. Histologically proven pancreas ductal adenocarcinoma
6. Available FFPE from pancreatic tumor sample with > 10% of tumor cells (assessed by a local expert pancreatic pathologist)
7. No prior chemotherapy or radiation for pancreatic cancer (except one cycle of mFOLFIRINOX during waiting time for GEM + signature) or resection of pancreatic cancer
8. Age ≥18 years old and ≤ 80 years old if geriatric standardized evaluation validates the study chemotherapy regimen administration for patients between 75-80
9. Written informed consent obtained from patient before any protocol related intervention
10. Acceptation and ability to conform to the protocol requirement during all the duration of the investigation including treatment, scheduled visits, clinical and biological examinations and follow up
11. Women of childbearing potential must agree to use contraception during treatment and for at least 15 months after discontinuation of the experimental treatments. Men who have sexual relationship with women of childbearing potential must agree to use contraception during treatment and for at least 12 months after discontinuation of the experimental treatments
12. Patient affiliated to French social security

Exclusion criteria 22

1. Strictly resectable or locally advanced PDAC according to NCCN criteria
2. Distant metastases (including inter aortic lymph nodes)
3. Any condition that contraindicates the use of IRINOTECAN, OXALIPLATIN, 5 FU, GEMCITABINE or NAB-PACLITAXEL
4. Partial or complete DPD deficiency (uracilemia ≥ 16 ng/mL)
5. Any progressive pathology not stabilized over the past 6 months: liver impairment, renal impairment, respiratory or cardiac failure
6. Other concomitant cancer or a history of cancer during the previous 3 years, except for localized cancer in situ, basal or squamous cell skin cancer adequately treated
7. Other interventional clinical trial except for non-interventional trial (ie not modifying 1-year EFS)
8. QT/QTc interval > 450 msec for men and > 470 msec for women
9. Pregnant or breastfeeding woman
10. Known Gilbert's syndrome or known homozygosity for UGAT1A1*28 polymorphism
11. Treatment with millepertuis
12. Uncompensated asthma
13. Potentially severe infection < 7 days
14. Inflammatory bowel disease and/or intestinal obstruction
15. Known severe allergy to contrast dye (for CT or MRI) without possible substitution
16. Hypersensitivity to the active substance or to one of the excipients of one of the study treatments
17. Treatment with brivudine within 4 weeks prior to the administration of protocol treatment
18. Concomitant treatment with a strong inhibitor (i.e. ketoconazole) or inducer (i.e. rifampicin, carbamazepine, phenobarbital, phenytoin, apalutamide) of cytochrome P450 3A4 or 2C8 (CYP3A4 or CYP2C8)
19. Patient who has received a live attenuated vaccine (against yellow fever, chickenpox, shingles, measles, mumps, rubella, tuberculosis, rotavirus) in the 6 weeks prior to randomization
20. Patient with sensitive peripheral neuropathy with functional discomfort
21. Impossibility of undergoing medical monitoring during the trial for geographical, social, or psychological reasons
22. Patient who is under judicial protection and patient who is legally institutionalized or under guardianship or not able to give consent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1-year EFS in the GEM + randomized population

Secondary endpoints 11

1. ORR is defined as % of patients with a complete or a partial response
2. TRG evaluated by Ryan Simplified TRG on the primary tumor after surgery.
3. Resection rates will be evaluated after 4 months of neoadjuvant chemotherapy in both arms
4. OS is defined as the time between the date of randomization and the date of death (whatever the cause)
5. PFS is defined as the time between the date of randomization and the date of first recurrence or death (all causes). PFS will be evaluated on patients without resection
6. DFS is defined as the time between the date of randomization and the date of first recurrence or death. DFS will be evaluated on patients with resection
7. TTR is defined as the time between the date of randomization and the date of first recurrence or death linked to the cancer
8. Percentage of NAC completion (4 months planned) is defined as the percentage of patients who received the 4 cycles of NAC
9. Percentage of adjuvant chemotherapy is defined as the percentage of patients who received at least one dose of adjuvant chemotherapy
10. Toxicities during the NAC will be collected before each NA cycle and will be graded according to NCI-CTCAE v5.0
11. Quality of life will be assessed with QLQC30 and QLQPAN26. It is defined as the time between the date of randomization and the date of death or date of first deterioration by more than five points on the global health scale in comparison with the score at baseline

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondation Franc.Cancerologie Digestive

Sponsor organisation

Fondation Franc.Cancerologie Digestive

Address

7 Boulevard Jeanne D Arc

City

Dijon

Postcode

21000

Country

France

Scientific contact point

Organisation

Fondation Franc.Cancerologie Digestive

Contact name

Coordinator

Public contact point

Organisation

Fondation Franc.Cancerologie Digestive

Contact name

Coordinator

Locations

1 EU/EEA country · 26 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications