Risk-adapted Adjuvant Chemotherapy Guided by the Tumour Stage for Operated Pancreatic Adenocarcinoma Following Neoadjuvant Chemotherapy With mFOLFIRINOX

NCT07044453 | Recruiting Phase 2 DMC

• 2 other identifiers: 2021/0377/HP2024-519048-33-00
• Study Type: interventional
• Target: 390
• Locations: 1 country
• Sites: 1

Brief Summary

Induction mFOLFIRINOX has become the standard in the management of locally advanced and borderline adenocarcinoma. Following the results of the PREOPANC-01 JASP-05, NEONAX studies it is expected that the neoadjuvant approach will be the standard strategy soon in patients with resectable PAC. The results of the PANACHE-01 trial confirm the feasibility of the neoadjuvant approach in the setting of resectable adenocarcinoma. Two randomized phase III studies, on the same design as PANACHE-01 are currently underway comparing neoadjuvant and adjuvant chemotherapy with mFOLFIRINOX for resectable PAC, (Alliance AO21806, NCT04340141; PREOPANC3, NCT04927780). Despite the improvement of oncosurgical management, recurrence of PAC soon after resection occurs frequently, leading to the dismal prognosis and unnecessary surgery-related loss of quality of life. Thus, there is urgent need for development of innovative and new strategies to decrease postoperative recurrence. Important residual tumor load after NAT suggests a primary resistance of the tumor or the selection of resistant clones. The most innovative aspect of this study will be to adapt the adjuvant chemotherapy strategy to the pathological response (downstaging) in patients who will have R0-R1 resection after neoadjuvant mFOLFIRINOX, taking into account the chemoresistance/sensibility status of the tumor.

Conditions

Resected Pancreatic Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Disease Free Survival

  The primary efficacy endpoint is the Disease Free Survival at 2 years (DFS), defined as the time from randomization to locoregional recurrence, occurrence of distant metastases or second pancreatic cancer, or death (all causes) whichever occurred first. Patients free of events will be censored at the date of the last disease evaluation either during study treatment period or during follow-up period

  from enrollment up to 5 years

• Overall Survival

  The primary efficacy endpoint is the Overall Survival at 3 years(OS), defined as the time from randomization to the death from any cause. Alive patient will be censored at last date known to be alive either during study treatment period or during follow-up period

  from enrollment up to 7 years

Secondary Outcomes (7)

• Incidence and grade for Adverse Events (AEs)

  from enrollment up to 7 years

• metastatic recurrence free survival in both arms

  from enrollment up to 7 years

• rate of patients with early recurrence

  from enrollment up to 5 years

• evolution of the health-related quality of life

  from enrollment up to 7 years

• evolution of the health-related quality of life

  from enrollment up to 7 years

Study Arms (2)

Experimental group - Arm A:

EXPERIMENTAL

Adjuvant chemotherapy guided by pathological analysis (downstaging) * pT1-2/N0/R0 status: 3 months mFOLFIRINOX adjuvant chemotherapy (no change in chemotherapy regimen compared to neoadjuvant setting) * pT3-4 or N+ or R1 status: 3 months Gemcitabine with NabPaclitaxel adjuvant chemotherapy (change in chemotherapy regimen compared to neoadjuvant setting).

Drug: Gem/Nabpaclitaxel infusion; Drug: mFOLFIRINOX infusion

Control group - Arm B

ACTIVE COMPARATOR

3 months mFOLFIRINOX adjuvant chemotherapy regardless of pathological analysis

Drug: mFOLFIRINOX infusion

Interventions

mFOLFIRINOX infusion DRUG

Downstaging and pathological response is empirically define as T1-2/N0/R0 status. In that setting the patients will receive mFOLFIRINOX adjuvant chemotherapy 3 months.

Control group - Arm B; Experimental group - Arm A:

Gem/Nabpaclitaxel infusion DRUG

Downstaging and pathological response is empirically define as T1-2/N0/R0 status. If the anatomopathological analysis shows a lesion classified as T3-4 or N+ or R1, an adjuvant chemotherapy based on Gemcitabine with Nab Paclitaxel will be proposed for a period of 3 months.

Experimental group - Arm A:

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed resected pancreatic adenocarcinoma (R0 or R1) that has received 3 months of neoadjuvant mFOLFIRINOX, including anatomically resectable and borderline resectable tumors, in accordance with the definitions and therapeutic considerations provided in the TNCD (2024) and ESMO (2023) guidelines.
• Performance status ECOG 0 or 1
• CA 19-9 level ≤ 200 U/ml
• Age 18 years or over
• Absolute neutrophil count \> 1,500 mm³, platelet count \> 100,000 mm³, creatinine clearance (according to MDRD equation) \> 50 ml/min, haemoglobin level \> 10 g/dl (transfusions are authorized)
• For men participating in the study, contraception is required during the trial and for 12 months after stopping chemotherapy treatment.
• Patient affiliated with, or beneficiary of, a social security (national health insurance) plan
• Patient able to comply with the study protocol, in the investigator's judgment
• Read and understood the information letter and signed the consent form

You may not qualify if:

• Metastatic PAC on post-operative imaging
• Cholangiocarcinoma, ampullary carcinoma or other non-PAC pancreatic tumors
• Non-controlled congestive heart failure, non-treated angina, recent myocardial infarction (in the previous year), non-controlled AHT (SBP \> 160 mm Hg or DBP \> 100 mm Hg, despite optimal drug treatment), long QT
• Major non-controlled infection, chronic infectious diseases, immune deficiency syndromes
• Premalignant hematologic disorders, e.g. myelodysplastic syndrome
• Severe liver failure
• Past or current history of malignancies except for the indication under this study and curatively treated basal and squamous cell carcinoma of the skin, in situ carcinoma of the cervix, other malignant disease without recurrence after at least 2 years of follow-up
• Any medical, psychological or social situation that (in the investigator's opinion) could limit the patient's compliance with the protocol or the ability to obtain or interpret data or to understand the conditions required for his/her participation in the protocol or render him/her unable to give informed consent
• Pregnant or breastfeeding women and women of childbearing age not using effective means of contraception
• Person participating in another interventional research having the same primary endpoint
• Person deprived of liberty by an administrative or judicial decision or person placed under judicial protection, under guardianship or curatorship
• Uracilemia ≥ 150 ng/ml (suggestive of complete DPD deficiency)
• Contraindication to study adjuvant chemotherapy treatments in accordance with the SmPCs of the products used in this trial (Gemcitabine, Nab-Paclitaxel, Oxaliplatin, Folinic Acid or Leucovorin, Irinotecan, Fluorouracil)

Sponsors & Collaborators

• Partenariat de Recherche en Oncologie DIGEstive - PRODIGE: collaborator
• University Hospital, Rouen: lead
• Federation de recherche en chirurgie digestive (FRENCH): collaborator

Study Sites (1)

CHU de Rouen

Rouen, France

RECRUITING

Central Study Contacts

Lilian SCHWARZ, PUPH

CONTACT

+332 32 88 84 18; lilian.schwarz@chu-rouen.fr

Mylene HERVET

CONTACT

mylene.hervet@chu-rouen.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2025
• First Posted: July 1, 2025
• Study Start: December 8, 2025
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): September 1, 2032
• Last Updated: February 17, 2026

Record last verified: 2026-02

Locations

FR (1)