Preoperative/Neoadjuvant Therapy and Vascular Debranching Followed by Resection for Locally Advanced Pancreatic Cancer (PREVADER)

Pancreatic cancer continues to have a poor prognosis. Many patients are diagnosed with advanced disease. In a considerable proportion of these patients, the tumor has contact with or invades into arterial blood vessels supplying the liver or bowel. Moreover, some patients have anatomical variations or Stenosis of these vessels. All such cases require a surgical reconstruction of the blood vessels upon pancreatic cancer resection in order to prevent that the liver or bowel are not sufficiently supplied with blood anymore. Performing such arterial reconstruction in one operation along with tumor resection is associated with a relevant risk of complications or even death.

This trial evaluates if the approach of 'visceral debranching', i.e. surgical reconstruction of arterial blood vessels supplying the liver or bowel, prior to chemotherapy and finally tumor resection in patients with locally advanced pancreatic cancer, is feasible.

Study Overview

• Status: Terminated
• Conditions: Pancreas Cancer
• Intervention / Treatment: Procedure: Visceral Debranching

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Halle (Saale), Germany, 06120
    • University Hospital, Dpt. of Visceral, Vascular and Endocrine Surgery
  • Heidelberg, Germany, 69120
    • University Hospital
  • Ulm, Germany, 89081
    • University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Pancreatic cancer (pancreatic ductal adenocarcinoma, Intraductal papillary mucinous neoplasm (IPMN) - derived adenocarcinoma, adenosquamous carcinoma), diagnosed by preoperative biopsy or cytology or intraoperative biopsy during the visceral debranching procedure

• Evidence of locally advanced disease which is considered unresectable due to arterial invasion on CT or MRI according to National Comprehensive Cancer Network (NCCN) and International Study Group of Pancreatic Surgery (ISGPS) criteria:

  • Tumor encasement (>180°) of the superior mesenteric artery or celiac trunk
  • Tumor encasement (>180°) of a short segment of the hepatic artery

OR

Anatomic variation of the visceral arteries with vascularization of the liver or mesentery via collaterals which need to be ligated during tumor resection (e.g. gastroduodenal artery), as shown on CT or MRI

OR

High-grade stenosis or occlusion of either the celiac trunk or the superior mesenteric artery with vascularization of the liver or mesentery via collaterals which need to be ligated during tumor resection (e.g. gastroduodenal artery), as shown on CT or MRI, which is not amenable to endovascular revascularization

• Invasion of the portal or superior mesenteric vein may be present, but must be considered resectable (involvement with distortion or narrowing of the vein or occlusion of the vein with suitable vessel proximal and distal, allowing for safe resection and replacement) according to National Comprehensive Cancer Network (NCCN) and International Study Group of Pancreatic Surgery (ISGPS) criteria (11, 12)
• Provision of written informed consent prior to performance of study-specific procedures or assessments and willingness to comply with treatment and follow-up

Exclusion Criteria

• Histologically proven peritoneal carcinomatosis (biopsies of macroscopically suspicious findings must be taken at the beginning of the operation and be analyzed immediately by fresh frozen section)
• Histologically proven distant metastatic disease
• Co-morbidities, organ function or physical status precluding visceral debranching or intensive neoadjuvant combination chemotherapy, as judged by the treating physicians
• Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with the patient's safety, provision of informed consent, or compliance with study procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Intervention; After trial enrolment, patients undergo visceral debranching. After visceral debranching, patients proceed to neoadjuvant chemotherapy. The therapy as such is not a formal part of the trial protocol. The specific chemotherapy regimen and its duration are decided individually by treating physicians. Tumor resection should be performed two to four weeks after completion of chemotherapy. Prior to resection, re-staging and verification of vascular reconstruction patency are carried out. The specific procedure for tumor resection and intestinal tract reconstruction is at the choice of the treating surgeon. It should follow oncological principles and aim at complete removal of the tumor and regional lymph nodes. Usually, resection will be done as pancreatoduodenectomy with or without distal gastrectomy (Whipple's procedure or pylorus-preserving Whipple's procedure), distal pancreatectomy with splenectomy, or total pancreatectomy with splenectomy.

Procedure: Visceral Debranching; Visceral debranching is defined as a vascular reconstruction with the aim of ensuring a sufficient arterial blood flow to the mesentery and liver after the subsequently planned tumor resection, which usually comprises ligation of the gastroduodenal artery or other relevant collateral vessels. All open vascular procedures can be employed for visceral debranching. Examples are aorto-visceral or iliaco-visceral bypasses using autologous vein or an allogeneic graft, or re-insertion of the superior mesenteric artery or celiac trunk into the aorta.; Other Names: Revascularisation of visceral arteries

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of visceral debranching	Proportion of patients proceeding to neoadjuvant chemotherapy (at least one dose administered within six weeks from the debranching procedure) among all patients undergoing visceral debranching	Six weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Completion of therapy	Proportion of patients proceeding to attempted tumor resection among all patients undergoing visceral debranching	Three months
Completeness of resection	Proportion of patients with clear resection margins (R0) upon pancreatic cancer resection following visceral debranching and neoadjuvant chemotherapy among all patients undergoing visceral debranching	Three months
Perioperative morbidity (visceral debranching)	Perioperative in-hospital morbidity associated with the visceral debranching procedure, measured according to the Clavien-Dindo-Classification of surgical complications	Four weeks
Perioperative morbidity (pancreatic cancer resection)	Perioperative in-hospital morbidity associated with pancreatic cancer resection, measured according to the Clavien-Dindo-Classification of surgical complications	Four weeks
Toxicity of chemotherapy	Toxicity during neoadjuvant chemotherapy, measured according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0	Three months
Progression-free survival	Time between time between first diagnosis, which is assumed to be equivalent to study enrolment, and documented progression. For patients who are not resected, progression-free survival will be defined as zero	Three years
Recurrence-free survival	Time between resection and the appearance of local recurrence, peritoneal carcinomatosis, or distant metastases. For patients who are not resected, recurrence-free survival will be defined as zero	Three years
Overall survival	Time between time between first diagnosis, which is assumed to be equivalent to study enrolment, and death, independent of the cause of death	Three years

Collaborators and Investigators

• Sponsor: Ulrich Ronellenfitsch, MD
• Investigators: Principal Investigator: Jörg Kleeff, MD, Martin-Luther-Universität Halle-Wittenberg

Publications and helpful links

General Publications

• Ronellenfitsch U, Michalski CW, Michl P, Krug S, Ukkat J, Kleeff J. Pre-operative/Neoadjuvant Therapy and Vascular Debranching Followed by Resection for Locally Advanced Pancreatic Cancer (PREVADER): Clinical Feasibility Trial. Front Med (Lausanne). 2021 May 24;8:588375. doi: 10.3389/fmed.2021.588375. eCollection 2021.

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2020
• Primary Completion (Actual): December 4, 2024
• Study Completion (Actual): December 4, 2024

Study Registration Dates

• First Submitted: October 21, 2019
• First Submitted That Met QC Criteria: October 21, 2019
• First Posted (Actual): October 23, 2019

Study Record Updates

• Last Update Posted (Actual): December 9, 2024
• Last Update Submitted That Met QC Criteria: December 4, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Neoadjuvant chemotherapy; Tumor resection; Arterial Invasion; Arterial reconstruction
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: 2019-152

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No