- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04571294
Para-aortic Lymphnodes Removal During Upfront Pancreaticoduodenectomy (PALN)
September 25, 2020 updated by: Alessandro Zerbi, Humanitas Hospital, Italy
Para-aortic Lymphnodes Removal During Upfront Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoa: Should it be Performed? A Multicentre Randomized Controlled Trial.
Pancreaticoduodenectomy (PD) associated with lymphadenectomy is the only curative option for patients affected by pancreatic ductal adenocarcinoma (PDAC).
In 2014, the International Study Group on Pancreatic Surgery (ISGPS) defined the "standard lymphadenectomy", that is mandatory during PD for PDAC.
Lymphadenectomy should include the removal of the hepatoduodenal ligament nodes (stations 5, 6, 12b1, 12b2, 12c according the classification of Japanese Pancreas Society), nodes along the hepatic artery (station 8a), the posterior surface of the pancreatic head (station 13a and 13b), the superior mesenteric artery (14a right lateral side, 14b right lateral side) and nodes of the anterior surface of the pancreatic head (stations 17a and 17b).
The inclusion of para-aortic lymphnodes (PALN) (station 16) in standard lymphadenectomy is still matter of debate.
Moreover, some retrospectives or prospective studies reported that the presence of PALN metastases has a significant negative prognostic impact.
Until now, no randomized studies comparing PD associated with standard lymphadenectomy with or without removal of PALN have been published.
The aim of this study is to evaluate if the removal of station 16 should be routinely included in standard lymphadenectomy during PD for PDAC.
Study Overview
Status
Recruiting
Intervention / Treatment
Detailed Description
Pancreaticoduodenectomy (PD) with lymphadenectomy is the current treatment of pancreatic ductal adenocarcinoma (PDAC).
The optimal lymphadenectomy during PD (standard versus extended) has been largely debated during the last two decades.
Four randomized controlled trials (RCTs) published afterward reported no survival benefit, and no arguments could be presented based on the evidence of these studies to support the role of extended lymphadenectomy during PD.
A similar conclusion was underlined also in two meta-analyses, the first from Michalski et al., in which 3 RCTs were analyzed, and the second from Iqbal et al., in which both RCTs and cohort studies were included, both of which showed no benefit of extended lymphadenectomy.
However, the definition of lymphadenectomy varied considerably between the RCTs.
For this reason, in 2014, the International Study Group on Pancreatic Surgery (ISGPS) defined the "standard lymphadenectomy" during PD for PDAC.
Lymphadenectomy should include the removal of the hepatoduodenal ligament nodes (stations 5, 6, 12b1, 12b2, 12c according the classification of Japanese Pancreas Society), nodes along the hepatic artery (station 8a), the posterior surface of the pancreatic head (station 13a and 13b), the superior mesenteric artery (14a right lateral side, 14b left lateral side) and nodes of the anterior surface of the pancreatic head (stations 17a and 17b).
Para-aortic lymph nodes (PALN; station 16) are considered as "extra-regional" lymph nodes.
Some questions about PALN still remain open: a) should the removal of station 16 be routinely included in the standard lymphadenectomy during PD for PDAC? b) in case of removal of station 16 and intraoperative demonstration of PALN metastases at frozen section, should PD be avoided ?
Several retrospective reports described that the prognosis of patients with metastatic PALN is significantly worse if compared with patients with negative PALN.
Two recent-metaanalyses have been published on this topic, confirming that PALN metastases correlated with poor prognosis in patients with PDAC.
However, these meta-analyses concluded that, due to the presence of some long survivors even in cases of PALN metastases, the definitive avoidance of PD in these cases needs further investigation.
Until now, no consensus in case of intraoperative metastatic PALN has been reached.
Moreover, it's not still clear if the removal of PALN during PD should be routinely performed.
Until now, no randomized studies comparing PD with or without removal of PALN have been published.
In 2014, during the consensus meeting of ISGPS, there was extensive discussion about PALN removal: no strong recommendation was formulated on dissecting station 16 routinely and it was not included in standard lymphadenectomy.
For this reason, we decided to plan this multicentric RCT that compares upfront PD with and without the removal of PALN, in order to evaluate if their removal should be routinely included in standard lymphadenectomy during PD for PDAC.
Study Type
Interventional
Enrollment (Anticipated)
180
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Gennaro Nappo, MD
- Phone Number: +39(0)282247701
- Email: gennaro.nappo@humanitas.it
Study Locations
-
-
Italy/Milan
-
Rozzano, Italy/Milan, Italy, 20089
- Recruiting
- Humanitas Research Hospital
-
Contact:
- Gennaro Nappo, MD
- Phone Number: +39(0)282247701
- Email: gennaro.nappo@humanitas.it
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- pre-operative radiological or histological diagnosis of pancreatic head PDAC, including PDAC arising from IPMN (invasive-IPMN) (in case of not confirmation of PDAC at final pathological examination, the case will be considered as a "drop out" and excluded from the study);
- upfront PD associated with standard lymphadenectomy.
Exclusion Criteria:
- PD performed after neoadjuvant treatment;
- PALN metastases diagnosed by a pre-operative PET-FDG (if performed);
- intraoperative distant metastases;
- R2 resection.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: group A
PALN removal
|
During pancreaticoduodenectomy, para-aortic lymphnodes (PALN) will be removed for the surgeon
|
No Intervention: group B
No PALN removal
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival (OS)
Time Frame: 48 months
|
The primary endpoint is to compare overall survival (OS) in patients with (group A) and without (group B) removal of PALN
|
48 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
PALN metastases
Time Frame: 12 months
|
to evaluate the rate of PALN metastases (for group A, only)
|
12 months
|
DFS in case of PALN metastases
Time Frame: 48 months
|
to evaluate the prognostic impact, in terms of Disease Free Survival (DFS), of PALN metastases (for group A, only)
|
48 months
|
OS in case of PALN metastases
Time Frame: 48 months
|
to evaluate the prognostic impact, in terms of OS, of PALN metastases (for group A, only)
|
48 months
|
predictive factors of PALN metastases
Time Frame: 12 months
|
to evaluate possible pre- and intra-operative predictive factors of PALN metastases (for group A, only): diameter of PALN, jaundice, preoperative biliary stent, time to surgery from diagnosis)
|
12 months
|
post-operative outcomes
Time Frame: 12 months
|
to compare post-operative outcomes in both study groups (overall morbidity, Clavien-Dindoo classification, post-operative pancreatic fistula, hemorrhage, biliary fistula, other surgical and medical compliation, 30-day and 90-day mortality)
|
12 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
May 26, 2020
Primary Completion (Anticipated)
May 26, 2024
Study Completion (Anticipated)
May 26, 2024
Study Registration Dates
First Submitted
September 21, 2020
First Submitted That Met QC Criteria
September 25, 2020
First Posted (Actual)
October 1, 2020
Study Record Updates
Last Update Posted (Actual)
October 1, 2020
Last Update Submitted That Met QC Criteria
September 25, 2020
Last Verified
September 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 451/20
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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