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

Pancreas Cancer Clinical Trial

— PREVADER  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04136769
• Other study ID #: 2019-152
• Status: Recruiting
• Phase: N/A
• Start date: February 7, 2020
• Est. completion date: July 2027

Study information

• Verified date: November 2023
• Source: Martin-Luther-Universität Halle-Wittenberg
• Contact: Ulrich Ronellenfitsch, MD
• Phone: +49 345 557 2327
• Email: ulrich.ronellenfitsch[@]uk-halle.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 28
• Est. completion date: July 2027
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pancreas Cancer
• Pancreatic Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Germany	University Hospital, Dpt. of Visceral, Vascular and Endocrine Surgery	Halle (Saale)
Germany	University Hospital	Heidelberg
Germany	University Hospital	Ulm

Sponsors (1)

Lead Sponsor	Collaborator
Ulrich Ronellenfitsch, MD

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Completion of therapy	Proportion of patients proceeding to attempted tumor resection among all patients undergoing visceral debranching	Three months
Secondary	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
Secondary	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
Secondary	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
Secondary	Toxicity of chemotherapy	Toxicity during neoadjuvant chemotherapy, measured according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0	Three months
Secondary	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
Secondary	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
Secondary	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