Resectable pancreatic adenocarcinoma neo-adjuvant FOLF(IRIN)OX-based chemotherapy - a multicenter, non-comparative, randomized, phase II trial (PANACHE01-PRODIGE48 study)

Lilian Schwarz, Dewi Vernerey, Jean-Baptiste Bachet, Jean-Jacques Tuech, Fabienne Portales, Pierre Michel, Antonio Sa Cunha, Lilian Schwarz, Dewi Vernerey, Jean-Baptiste Bachet, Jean-Jacques Tuech, Fabienne Portales, Pierre Michel, Antonio Sa Cunha

Abstract

Background: At time of diagnosis, less than 10% of patients with pancreatic adenocarcinomas (PDAC) are considered to be immediately operable (i.e. resectable). Considering their poor overall survival (OS), only tumours without vascular invasion (NCCN 2017) should be considered for resection, i.e. those for which resection with disease-free margins (R0) is theoretically possible in absence of presurgery treatment. With regard to high R1 rates and undetectable locoregional and/or metastatic spreading prior to surgery explain (at least in part) the observed 1-year relapse and mortality rates of 50 and 25%, respectively. Today, upfront surgery followed by adjuvant chemotherapy is the reference treatment in Europe. The main limitation of the adjuvant approach is the low rate of completion of the full therapeutic sequence. Indeed, only 47 to 60% patients received any adjuvant therapy after resection compared to more than 75% for neoadjuvant therapy. No previous prospective study has compared this approach to a neoadjuvant FOLFIRINOX or FOLFOX chemotherapy for resectable PDAC.

Methods: PANACHE01-PRODIGE48 is a prospective multicentre controlled randomized non comparative Phase II trial, evaluating the safety and efficacy of two regimens of neo-adjuvant chemotherapy (4 cycles of mFOLFIRINOX or FOLFOX) relative to the current reference treatment (surgery and then adjuvant chemotherapy) in patients with resectable PDAC. The main co-primary endpoints are OS rate at 12 months and the rate of patients undergoing the full therapeutic sequence.

Discussion: The "ideal" cancer treatment for resectable PDAC would have the following characteristics: administration to the highest possible proportion of patients, ability to identify fast-progressing patients (i.e. poor candidates for surgery), a low rate of R1 resections (through optimisation of local disease control), and an acceptable toxicity profile. The neoadjuvant approach may meet all these criteria. With respect to published data on the efficacy of FOLFOX and mFOLFIRINOX, these two regimens are potential candidates for neoadjuvant use in the aim to optimising oncological outcomes in resectable PDAC.

Trial registration: ClinicalTrials.gov , NCT02959879 . Trial registration date: November 9, 2016.

Keywords: Neoadjuvant chemotherapy; Randomized study; Resectable pancreatic adenocarcinoma; Surgery; mFOLFIRINOX.

Conflict of interest statement

Ethics approval and consent to participate

The study protocol was approved by the Institutional Review Board, the Nord Ouest IV ethics committee on the 26th of May 2016 and the Agence Nationale de sécurité des médicaments et des produits de santé (ANSM) on the 19th of July 2016 under the number 2015–001851-65. The institutional promoter is the University Hospital of Rouen, France. The trial has been registered on the ClinicalTrial.gov website under the identification number NCT02959879, on November 9, 2016. The study complies with the Declaration of Helsinki rules and the principles of Good Clinical Practice guidelines. Informed consent will be obtained from each patient in written form prior to randomization and an information leaflet will be given to each patient prior to inclusion in the study. Patient safety and all potential threats to patient safety will be monitored by an independent monitoring board which will be able, taking into account undesirable events and the level of post-operative mortality, recommend the discontinuation of one of the treatments evaluated.

Consent for publication

Not applicable

Competing interests

None of the authors have any competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Protocol overview. MRI: Magnetic resonance imaging; PDAC: Pancreatic duct adenocarcinoma; TDM TAP: CT-scan Thorax Abdomen and Pelvis

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Source: PubMed

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