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

• Published in: BMC cancer 2023-08, Vol.23 (1), p.728-728, Article 728
• Main Authors: van Dam, J L, Verkolf, E M M, Dekker, E N, Bonsing, B A, Bratlie, S O, Brosens, L A A, Busch, O R, van Driel, L M J W, van Eijck, C H J, Feshtali, S, Ghorbani, P, de Groot, D J A, de Groot, J W B, Haberkorn, B C M, de Hingh, I H, van der Holt, B, Karsten, T M, van der Kolk, M B, Labori, K J, Liem, M S L, Loosveld, O J L, Molenaar, I Q, Polée, M B, van Santvoort, H C, de Vos-Geelen, J, Wumkes, M L, van Tienhoven, G, Homs, M Y V, Besselink, M G, Wilmink, J W, Groot Koerkamp, B
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; Adenocarcinoma; Adjuvant therapy; Adjuvant treatment; Adjuvants, Immunologic - therapeutic use; Antigens; Antimitotic agents; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biomarkers; Cancer; Cancer therapies; Care and treatment; Chemotherapy; Chemotherapy, Adjuvant; Clinical trials; Comparative analysis; Data collection; Diagnosis; Dosage and administration; Enzymes; Fluorouracil - therapeutic use; General Data Protection Regulation; Humans; Irinotecan; Irinotecan - therapeutic use; Leucovorin - therapeutic use; Medical imaging; Medicin och hälsovetenskap; Metastasis; mFOLFIRINOX; Multicenter Studies as Topic; Neoadjuvant therapy; Neoadjuvant Therapy - methods; Oncology, Experimental; Overall survival; Oxaliplatin; Oxaliplatin - therapeutic use; Pancreatic cancer; Pancreatic Neoplasms; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - surgery; Patients; Quality of life; Randomized controlled trial; Randomized Controlled Trials as Topic; Relapse; Skin cancer; Study Protocol; Surgery; Surgical outcomes; Survival
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-023-11141-5

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. 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/m , leucovorin 400 mg/m , irinotecan 150 mg/m at day 1, followed by 46 h continuous infusion of 5-fluorouracil 2400 g/m ). 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. The multicenter PREOPANC-3 trial compares perioperative mFOLFIRINOX with adjuvant mFOLFIRINOX in patients with resectable pancreatic cancer. Clinical Trials: NCT04927780. Registered June 16, 2021.