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

NCT ID: NCT04136769

Last Updated: 2024-12-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-07
• Study Completion Date: 2024-12-04

Brief Summary

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.

Conditions

Pancreas Cancer

Keywords

Arterial Invasion; Arterial reconstruction; Neoadjuvant chemotherapy; Tumor resection

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Visceral Debranching

Intervention Type: PROCEDURE

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.

Interventions

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.

Intervention Type: PROCEDURE

Other Intervention Names

Revascularisation of visceral arteries

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ulrich Ronellenfitsch, MD

OTHER

Sponsor Role: lead

Responsible Party

Ulrich Ronellenfitsch, MD

Study Coordinator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jörg Kleeff, MD

Role: PRINCIPAL_INVESTIGATOR

Martin-Luther-Universität Halle-Wittenberg

Locations

University Hospital, Dpt. of Visceral, Vascular and Endocrine Surgery

Halle, , Germany

University Hospital

Heidelberg, , Germany

University Hospital

Ulm, , Germany

Countries

Germany

References

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.

Reference Type: DERIVED

PMID: 34109185 (View on PubMed)

Other Identifiers

2019-152

Identifier Type: -

Identifier Source: org_study_id