Preoperative/Neoadjuvant Therapy and Vascular Debranching Followed by Resection for Locally Advanced Pancreatic Cancer (PREVADER)
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| ClinicalTrials.gov Identifier: NCT04136769 |
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Recruitment Status :
Recruiting
First Posted : October 23, 2019
Last Update Posted : November 29, 2023
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Pancreas Cancer | Procedure: Visceral Debranching | Not Applicable |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 28 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Intervention Model Description: | Exact single stage design |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Preoperative/Neoadjuvant Therapy and Vascular Debranching Followed by Resection for Locally Advanced Pancreatic Cancer |
| Actual Study Start Date : | February 7, 2020 |
| Estimated Primary Completion Date : | July 2024 |
| Estimated Study Completion Date : | July 2027 |
| Arm | Intervention/treatment |
|---|---|
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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 Name: Revascularisation of visceral arteries |
- Feasibility of visceral debranching [ Time Frame: Six weeks ]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
- Completion of therapy [ Time Frame: Three months ]Proportion of patients proceeding to attempted tumor resection among all patients undergoing visceral debranching
- Completeness of resection [ Time Frame: Three months ]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) [ Time Frame: Four weeks ]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) [ Time Frame: Four weeks ]Perioperative in-hospital morbidity associated with pancreatic cancer resection, measured according to the Clavien-Dindo-Classification of surgical complications
- Toxicity of chemotherapy [ Time Frame: Three months ]Toxicity during neoadjuvant chemotherapy, measured according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0
- Progression-free survival [ Time Frame: Three years ]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 Frame: Three years ]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 Frame: Three years ]Time between time between first diagnosis, which is assumed to be equivalent to study enrolment, and death, independent of the cause of death
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
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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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04136769
| Contact: Ulrich Ronellenfitsch, MD | +49 345 557 2327 | ulrich.ronellenfitsch@uk-halle.de |
| Germany | |
| University Hospital, Dpt. of Visceral, Vascular and Endocrine Surgery | Recruiting |
| Halle (Saale), Germany, 06120 | |
| Contact: Ulrich Ronellenfitsch, MD +49-345-5572327 ulrich.ronellenfitsch@uk-halle.de | |
| University Hospital | Recruiting |
| Heidelberg, Germany, 69120 | |
| Contact: Rosa Klotz, MD rosa.klotz@med.uni-heidelberg.de | |
| University Hospital | Recruiting |
| Ulm, Germany, 89081 | |
| Contact: Felix Hüttner, MD +49 731 500 53501 Felix.Huettner@uniklinik-ulm.de | |
| Principal Investigator: | Jörg Kleeff, MD | Martin-Luther-Universität Halle-Wittenberg |
| Responsible Party: | Ulrich Ronellenfitsch, MD, Study Coordinator, Martin-Luther-Universität Halle-Wittenberg |
| ClinicalTrials.gov Identifier: | NCT04136769 |
| Other Study ID Numbers: |
2019-152 |
| First Posted: | October 23, 2019 Key Record Dates |
| Last Update Posted: | November 29, 2023 |
| Last Verified: | November 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Arterial Invasion Arterial reconstruction Neoadjuvant chemotherapy Tumor resection |
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Pancreatic Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms |
Endocrine Gland Neoplasms Digestive System Diseases Pancreatic Diseases Endocrine System Diseases |