Perioperative or adjuvant mFOLFIRINOX for resectable pancreatic cancer (PREOPANC-3): study protocol for a multicenter randomized controlled trial

J. L. van Dam, E. M.M. Verkolf, the Dutch Pancreatic Cancer Group (DPCG), E. N. Dekker, B. A. Bonsing, S. O. Bratlie, L. A.A. Brosens, O. R. Busch, L. M.J.W. van Driel, C. H.J. van Eijck, S. Feshtali, P. Ghorbani, D. J.A. de Groot, J. W.B. de Groot, B. C.M. Haberkorn, I. H. de Hingh, B. van der Holt, T. M. Karsten, M. B. van der Kolk, K. J. LaboriM. S.L. Liem, O. J.L. Loosveld, I. Q. Molenaar, M. B. Polée, H. C. van Santvoort, J. de Vos-Geelen, M. L. Wumkes, G. van Tienhoven, M. Y.V. Homs, M. G. Besselink, J. W. Wilmink, B. Groot Koerkamp

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Abstract

BACKGROUND: Surgical resection followed by adjuvant mFOLFIRINOX (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) is currently the standard of care for patients with resectable pancreatic cancer. The main concern regarding adjuvant chemotherapy is that only half of patients actually receive adjuvant treatment. Neoadjuvant chemotherapy, on the other hand, guarantees early systemic treatment and may increase chemotherapy use and thereby improve overall survival. Furthermore, it may prevent futile surgery in patients with rapidly progressive disease. However, some argue that neoadjuvant therapy delays surgery, which could lead to progression towards unresectable disease and thus offset the potential benefits. Comparison of perioperative (i.e., neoadjuvant and adjuvant) with (only) adjuvant administration of mFOLFIRINOX in a randomized controlled trial (RCT) is needed to determine the optimal approach. METHODS: This multicenter, phase 3, RCT will include 378 patients with resectable pancreatic ductal adenocarcinoma with a WHO performance status of 0 or 1. Patients are recruited from 20 Dutch centers and three centers in Norway and Sweden. Resectable pancreatic cancer is defined as no arterial contact and ≤ 90 degrees venous contact. Patients in the intervention arm are scheduled for 8 cycles of neoadjuvant mFOLFIRINOX followed by surgery and 4 cycles of adjuvant mFOLFIRINOX (2-week cycle of oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, irinotecan 150 mg/m2 at day 1, followed by 46 h continuous infusion of 5-fluorouracil 2400 g/m2). Patients in the comparator arm start with surgery followed by 12 cycles of adjuvant mFOLFIRINOX. The primary outcome is overall survival by intention-to-treat. Secondary outcomes include progression-free survival, resection rate, quality of life, adverse events, and surgical complications. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after the inclusion of 378 patients in 36 months, with analysis planned 18 months after the last patient has been randomized. DISCUSSION: The multicenter PREOPANC-3 trial compares perioperative mFOLFIRINOX with adjuvant mFOLFIRINOX in patients with resectable pancreatic cancer. TRIAL REGISTRATION: Clinical Trials: NCT04927780. Registered June 16, 2021.

Original languageEnglish
Article number728
JournalBMC Cancer
Volume23
Issue number1
DOIs
Publication statusPublished - Dec 2023

Bibliographical note

Funding Information:
We would like to acknowledge Judith Verhagen – Oldenampsen and the patient association Living With Hope Foundation for their contribution to the development of the study protocol. The principal investigator will be responsible for the publication of the study outcomes. The results will be reported during symposia and national and international meetings. The final trial results will be submitted to a peer reviewed medical journal. Authorships will be based on the Recommendations by the International Committee of Medical Journal Editors.

Funding Information:
The PREOPANC-3 trial is supported by the Dutch Cancer Society under project number 13417, ZonMw under project number 10140022010009, and Swedish Research Council under project number 2022–00300. The funding sources had no role in the design of this study and will have no role during its execution, analyses, interpretation of the data, or decision to submit results for publication.

Publisher Copyright:
© 2023, BioMed Central Ltd., part of Springer Nature.

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