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.
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
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
Parallel
Gem/Nabpaclitaxel infusion
DrugDownstaging 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.
mFOLFIRINOX infusion
DrugDownstaging and pathological response is empirically define as T1-2/N0/R0 status. In that setting the patients will receive mFOLFIRINOX adjuvant chemotherapy 3 months.
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
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
Incidence and grade for Adverse Events (AEs)
drug related AEs, drug related AE leading to dose reduction or discontinuation during treatment, SAE and SUSAR, according to NCI-CTCAE V5.0.
metastatic recurrence free survival in both arms
Time to metastatic recurrence defined as the time from randomization to occurrence of distant metastases.
rate of patients with early recurrence
Early recurrence \< 6 months after surgical randomization
evolution of the health-related quality of life
Health related quality of life EORTC QLQ-C30 questionnaire (European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire - Core 30). Scale rated from 0 to 100.
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University Hospital, Rouen
Lead sponsor
Partenariat de Recherche en Oncologie DIGEstive - PRODIGE
Collaborator
Federation de recherche en chirurgie digestive (FRENCH)
Collaborator
