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

Primary Purpose

Pancreas Cancer

Status

Recruiting

Phase

Not Applicable

Locations

Germany

Study Type

Interventional

Intervention

Visceral Debranching

About this trial

This is an interventional treatment trial for Pancreas Cancer focused on measuring Arterial Invasion, Arterial reconstruction, Neoadjuvant chemotherapy, Tumor resection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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

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

Sites / Locations

University Hospital, Dpt. of Visceral, Vascular and Endocrine SurgeryRecruiting
University HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Intervention

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Completion of therapy

Proportion of patients proceeding to attempted tumor resection among all patients undergoing visceral debranching

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

Perioperative morbidity (visceral debranching)

Perioperative in-hospital morbidity associated with the visceral debranching procedure, measured according to the Clavien-Dindo-Classification of surgical complications

Perioperative morbidity (pancreatic cancer resection)

Perioperative in-hospital morbidity associated with pancreatic cancer resection, measured according to the Clavien-Dindo-Classification of surgical complications

Toxicity of chemotherapy

Toxicity during neoadjuvant chemotherapy, measured according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0

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

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

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

Full Information

NCT ID

NCT04136769

First Posted

October 21, 2019

Last Updated

October 31, 2022

Sponsor

Ulrich Ronellenfitsch, MD

1. Study Identification

Unique Protocol Identification Number

NCT04136769

Brief Title

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

Acronym

PREVADER

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Recruiting

Study Start Date

February 7, 2020 (Actual)

Primary Completion Date

July 2024 (Anticipated)

Study Completion Date

July 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Ulrich Ronellenfitsch, MD

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pancreas Cancer

Keywords

Arterial Invasion, Arterial reconstruction, Neoadjuvant chemotherapy, Tumor resection

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Model Description

Exact single stage design

Masking

None (Open Label)

Allocation

N/A

Enrollment

28 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Intervention

Arm Type

Experimental

Arm Description

Intervention Type

Procedure

Intervention Name(s)

Visceral Debranching

Other Intervention Name(s)

Revascularisation of visceral arteries

Intervention Description

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.

Primary Outcome Measure Information:

Title

Feasibility of visceral debranching

Description

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

Time Frame

Six weeks

Secondary Outcome Measure Information:

Title

Completion of therapy

Description

Proportion of patients proceeding to attempted tumor resection among all patients undergoing visceral debranching

Time Frame

Three months

Title

Completeness of resection

Description

Time Frame

Three months

Title

Perioperative morbidity (visceral debranching)

Description

Perioperative in-hospital morbidity associated with the visceral debranching procedure, measured according to the Clavien-Dindo-Classification of surgical complications

Time Frame

Four weeks

Title

Perioperative morbidity (pancreatic cancer resection)

Description

Perioperative in-hospital morbidity associated with pancreatic cancer resection, measured according to the Clavien-Dindo-Classification of surgical complications

Time Frame

Four weeks

Title

Toxicity of chemotherapy

Description

Toxicity during neoadjuvant chemotherapy, measured according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0

Time Frame

Three months

Title

Progression-free survival

Description

Time Frame

Three years

Title

Recurrence-free survival

Description

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

Time Frame

Three years

Title

Overall survival

Description

Time between time between first diagnosis, which is assumed to be equivalent to study enrolment, and death, independent of the cause of death

Time Frame

Three years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Ulrich Ronellenfitsch, MD

Phone

+49 345 557 2327

ulrich.ronellenfitsch@uk-halle.de

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jörg Kleeff, MD

Organizational Affiliation

Martin-Luther-Universität Halle-Wittenberg

Official's Role

Principal Investigator

Facility Information:

Facility Name

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

City

Halle (Saale)

ZIP/Postal Code

06120

Country

Germany

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ulrich Ronellenfitsch, MD

Phone

+49-345-5572327

ulrich.ronellenfitsch@uk-halle.de

Facility Name

University Hospital

City

Ulm

ZIP/Postal Code

89081

Country

Germany

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Felix Hüttner, MD

Phone

+49 731 500 53501

Felix.Huettner@uniklinik-ulm.de

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34109185

Citation

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.

Results Reference

derived

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

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