Clinical trial NCT04136769: Preoperative/Neoadjuvant Therapy and Vascular Debranching Followed by Resection for Locally Advanced Pancreatic Cancer
Official title: Preoperative/Neoadjuvant Therapy and Vascular Debranching Followed by Resection for Locally Advanced Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Pancreas Cancer
Keywords: Arterial Invasion
Arterial reconstruction
Neoadjuvant chemotherapy
Tumor resection
Lead sponsor: Martin-Luther-Universität Halle-Wittenberg
Sponsor class: OTHER
First posted: 2019-10-23
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Exact single stage design
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Feasibility of visceral debranching
timeFrame: Six weeks
Secondary outcomes:
measure: Completion of therapy
timeFrame: Three months
measure: Completeness of resection
timeFrame: Three months
measure: Perioperative morbidity (visceral debranching)
timeFrame: Four weeks
measure: Perioperative morbidity (pancreatic cancer resection)
timeFrame: Four weeks
measure: Toxicity of chemotherapy
timeFrame: Three months
measure: Progression-free survival
timeFrame: Three years
measure: Recurrence-free survival
timeFrame: Three years
measure: Overall survival
timeFrame: Three years
Other outcomes:
Locations:
city: Halle (Saale)
country: Germany
facility: University Hospital, Dpt. of Visceral, Vascular and Endocrine Surgery
city: Heidelberg
country: Germany
facility: University Hospital
city: Ulm
country: Germany
facility: University Hospital
Study officials:
affiliation: Martin-Luther-Universität Halle-Wittenberg
name: Jörg Kleeff, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.