Pre-operative/Neoadjuvant Therapy and Vascular Debranching Followed by Resection for Locally Advanced Pancreatic Cancer (PREVADER): Clinical Feasibility Trial

Abstract

Introduction: Pancreatic cancer continues to have a poor outcome. Many patients are diagnosed with advanced disease, and in a considerable proportion, abutment or invasion of visceral arteries is present. Moreover, some patients have anatomical variations or stenosis of major visceral arteries requiring arterial reconstruction upon pancreatic cancer resection to avoid organ ischemia. Simultaneous arterial reconstruction during resection is associated with relevant morbidity and mortality. This trial evaluates the approach of visceral debranching, that is, arterial reconstruction, prior to neoadjuvant chemotherapy and tumor resection in patients with locally advanced, unresectable pancreatic cancer. Methods and Analysis: The trial includes patients with locally advanced, non-metastatic pancreatic cancer with arterial abutment or invasion (deemed primarily unresectable), variations in vascular anatomy, or stenosis of visceral arteries. The participants undergo visceral debranching, followed by current standard neoadjuvant chemotherapy (mFOLFIRINOX, gemcitabine-nab-paclitaxel, or other) and potential subsequent tumor resection. The primary outcome is feasibility, measured as the proportion of patients who start neoadjuvant therapy within 6 weeks of visceral debranching. The trial has an exact single-stage design. The proportion below which the treatment is considered ineffective is set at 0.7 (H0). The proportion above which the treatment warrants further exploration in a phase III trial is set at 0.9 (H1). With a power (1-beta) of 0.8 and a type 1 mistake (alpha) of 0.05, the required sample size is 28 patients. Feasibility of the approach will be assumed if 24 of the enrolled 28 patients proceed to neoadjuvant chemotherapy within 6 weeks from visceral debranching. Discussion: This trial evaluates a new treatment sequence, that is, visceral debranching followed by chemotherapy and resection, for pancreatic cancer with invasion or abutment of visceral arteries. The primary objective of the trial is to evaluate feasibility. Trial results will allow for estimating treatment effects and calculating the sample size of a randomized controlled trial, in which the approach will be tested if the feasibility endpoint is met. Clinical Trial Registration: clinicaltrials.gov, identifier: NCT04136769.

Keywords: arterial resection; feasibility trial; multimodal treatment approach; pancreatic cancer; preoperative chemotherapy.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Ronellenfitsch, Michalski, Michl, Krug, Ukkat and Kleeff.

Figures

Figure 1

Flow chart of the trial sequence.

Figure 2

Locally advanced pancreatic corpus adenocarcinoma considered unresectable due to arterial invasion on CT according to National Comprehensive Cancer Network and International Study Group of Pancreatic Surgery criteria. The red arrow delineates the tumor, which shows invasion of the superior mesenteric artery and celiac trunk both on sagittal (A) and transversal (B) images.

Figure 3

CT image of an anatomic variation of the visceral arteries with aplasia of the origin of the celiac trunk in the aorta (white arrow) and collateralization of the hepatic artery via a network of pancreatoduodenal collaterals (red arrow).