Condition category
Surgery
Date applied
16/04/2018
Date assigned
19/04/2018
Last edited
19/04/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Cancer of the body or tail (or distal part) of the pancreas is a devastating disease with a 5-year survival of 20% after intended curative treatment. Surgery is the only potentially curative treatment for pancreatic cancer but the postoperative morbidity (30%) and mortality rates (3-5%) are high. Minimally invasive (keyhole) surgery is on the rise worldwide. These procedures are performed through tiny incisions instead of one large opening. Several studies suggest that minimally invasive surgery is superior to conventional open surgery in terms of post-operative pain, morbidity and length of hospital stay. The introduction of minimally invasive pancreatic surgery has been much slower than for other surgical procedures, although the number of minimally invasive pancreatic resections performed has increased significantly in the past decade. Minimally invasive distal pancreatectomy (MIDP) has been shown in recent systematic reviews to have excellent outcomes in benign or premalignant disease concerning intraoperative and postoperative outcomes (i.e. blood loss, spleen preservation, postoperative morbidity, postoperative recovery) when compared to open distal pancreatectomy (ODP). However high-quality comparative studies of minimally invasive versus open surgery for distal pancreatic malignancies are scarce. Surgeons are faced with the decision to perform a MIDP or ODP in a patient with pancreatic cancer without clear evidence to support them. Especially oncological safety is not clearly demonstrated. At this moment a substantial amount of pancreatic cancer patients do not receive minimally invasive surgery and consequently may not benefit from possible shorter time to recovery and better quality of life after surgery, which especially for these patients with poor prognosis could be of substantial value. The aim of this study is to provide evidence on the potential benefits of minimally invasive surgery in patients with cancer of the body or tail of pancreas.

Who can participate?
Patients aged 18 or over who require resection of their distal pancreas for pancreatic ductal adenocarcinoma (PDAC), a type of pancreatic cancer

What does the study involve?
Participants are randomly allocated to either open or minimally invasive surgery. They receive a large abdominal dressing directly after surgery to mask their treatment (minimally invasive or open) by covering all incisions. This abdominal dressing is removed when recovery is complete, at day 5 after the operation or for medical reasons, such as for example suspicion of a wound infection. Participants complete quality of life questionnaires at the start of the study, and 1, 3 and 6 months after their surgery. Survival rates are calculated for 1, 2 and 3 year after the surgery.

What are the possible benefits and risks of participating?
Minimally invasive surgery may reduce the length of the hospital stay and improve postoperative morbidity and mortality. There are no added risks.

Where is the study run from?
This study is led by the University Hospital Southampton NHS Foundation Trust (UK) and Academic Medical Center Amsterdam (The Netherlands). Patients are recruited by 38 centres from 12 countries.

When is the study starting and how long is it expected to run for?
January 2018 to May 2023

Who is funding the study?
1. The Dutch Digestive Foundation (The Netherlands)
2. Academic Medical Center, Amsterdam (The Netherlands)

Who is the main contact?
1. Prof. Mohammed Abu Hilal
2. Prof. Marc Besselink

Trial website

http://www.e-mips.org/diploma/

Contact information

Type

Scientific

Primary contact

Prof Mohammed Abu Hilal

ORCID ID

Contact details

Southampton University Hospital NHS Foundation Trust
E level
Tremona Road
Southampton
SO16 6YD
United Kingdom

Type

Scientific

Additional contact

Prof Marc Besselink

ORCID ID

Contact details

Academic Medical Center
Department of Surgery
room G04-196
PO Box 22660
Amsterdam
1100 DD
Netherlands

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

The United Kingdom: RHMGSU0230, CPMS ID 37581; The Netherlands: NL63299.018.17

Study information

Scientific title

Distal pancreatectomy, minimally invasive or open, for malignancy (DIPLOMA): a pan-European, randomized controlled, multicenter, patient blinded, non-inferiority trial

Acronym

DIPLOMA

Study hypothesis

The trialists hypothesise that minimally invasive (laparoscopic and robot-assisted) distal pancreatectomy (MIDP) provides similar oncologic efficacy (i.e. microscopically radical resection margins (R0)) to open distal pancreatectomy (ODP) when performed in patients affected by PDAC.

Ethics approval

1. The United Kingdom: South West - Frenchay Research Ethics Committee, 08/03/2018, ref: 18/SW/0047
2. The Netherlands: Medical Ethics Review Committee of Academic Medical Center Amsterdam, 25/01/2018, ref: NL63299.018.17

Awaiting ethics approval in the following countries: Belgium, France, Germany, Italy, Norway, Russia, Slovenia, Spain, Sweden and USA

Study design

Multicenter; Randomized 1:1 ratio; Interventional; Patient-blinded

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

The Patient Information Sheet (English and Dutch) will be available on the following website: http://www.e-mips.org/diploma/

Condition

Proven or suspected pancreatic ductal adenocarcinoma (PDAC) in the pancreatic body or tail suitable for elective upfront distal pancreatectomy

Intervention

This study is designed for patients with an indication for distal pancreatectomy because of proven or suspected PDAC in the pancreatic body or tail. After inclusion, patients are randomly allocated in a 1:1 ratio to Minimally Invasive Distal Pancreatectomy or Open Distal Pancreatectomy, stratified by hospital volume and tumor involvement of other organs besides the pancreas and spleen. Randomization will take place as soon as the distal pancreatectomy can be planned. Patients will have a pre-surgery assessment conform local protocol.

Patients are blinded for the type of surgery they will receive. Patients will receive a large 40cm x 40cm abdominal dressing directly after surgery to mask their treatment (minimally invasive or open) by covering all incisions. This abdominal dressing will be removed when all criteria for functional recovery are met, and may be removed earlier when it’s day 5 postoperatively or for medical reasons, such as for example suspicion of a wound infection. If earlier inspection is required, attempts are made to maintain patient blinding. This blinding has been proven successfully in previous multicentre (European) trials. A complete double-blinding, including medical and nursing ward staff, is considered not feasible.

Patients are asked to complete QoL questionnaires at baseline, 1 month, 3 months and 6 months after their surgery. Survival rates will be calculated for 1, 2 and 3 year postoperative.

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measure

Microscopically radical resection margin (R0) (these can be in the transection margin of the pancreas but also in the anterior, superior, posterior, inferior margins, i.e. circumferential margins); Timepoint: postoperative

Secondary outcome measures

1. Intraoperative parameters (operative time, blood loss, blood transfusion and conversion)
2. Postoperative parameters (complications, mortality, re-interventions)
3. Pathology parameters (tumor size, lymph node retrieval, positive nodes, invasion, grading and staging)
4. Hospitalization parameters (time to functional recovery [measured daily using the functional recovery checklist], total hospital stay, readmission, intensive care admission)
5. Oncology parameters (use of (neo-)adjuvant chemotherapy, survival at 1, 2 and 3 years postoperative)
6. Quality of life, measured using the EORTC QLQ-30 and PAN-26 and EQ-5D-5L questionnaires at baseline and 1, 3 and 6 months postoperative
7. Costs

Overall trial start date

04/01/2018

Overall trial end date

01/05/2023

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

In order to be eligible to participate in this study, a patient must meet all of the following criteria:
1. Age ≥ 18 years
2. Elective indication for distal pancreatectomy for proven or suspected* PDAC
3. Upfront (without induction/downsizing radio- or chemotherapy) resectable PDAC in the pancreatic body or tail**
4. The tumor can be radically resected via both minimally invasive or open surgery according to the local treating team***
5. The patient is fit to undergo both open and minimally invasive distal pancreatectomy

*Pathology proof is not mandatory for two reasons, first it is not common practice in distal cancers to have this proof, so the decision for minimally invasive or open surgery will after the trial also depend on the ‘suspected’ diagnosis and second, there are even some concerns about the safety of endoscopic fine needle aspiration of distal pancreatic cancers with theoretical risk of peritoneal seeding
**Malignant degenerated cysts are not allowed in the study. Neoadjuvant chemotherapy is only allowed in case of an upfront resectable tumor (neoadjuvant)
**Multivisceral resections are allowed if, according to the local treating team, feasible with both, a minimally invasive and open approach

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

258 (129 per arm). The trialists expect every site to include 5-10 patients annually.

Participant exclusion criteria

Patients that meet any of the following criteria will be excluded from participation in this study:
1. ASA >3 (see appendix 17.3.2)
2. A medical history of chronic pancreatitis (according to the M-ANNHEIM criteria, see Appendix for detailed definition)
3. Second malignancy necessitating resection during the same procedure
4. Radiotherapy because of pancreatic cancer prior to distal pancreatectomy
5. Distant metastases (M1) including involved distant lymph nodes
6. Tumor involvement or abutment of major vessels (celiac trunk*, mesenteric artery or portomesenteric vein);
7. Pregnancy
8. Participation in another study with interference of study outcomes

*The celiac trunk should be 5mm clear from tumor

Recruitment start date

01/05/2018

Recruitment end date

01/05/2020

Locations

Countries of recruitment

Belgium, France, Germany, Italy, Netherlands, Norway, Russian Federation, Slovenia, Spain, Sweden, United Kingdom, United States of America

Trial participating centre

Academic Medical Center
Amsterdam
-
Netherlands

Trial participating centre

Erasmus Medical Center
Rotterdam
-
Netherlands

Trial participating centre

Radboud University Medical Center
Nijmegen
-
Netherlands

Trial participating centre

Catharina Hospital
Eindhoven
-
Netherlands

Trial participating centre

Utrecht Medical Center
Utrecht
-
Netherlands

Trial participating centre

St Antonius Hospital
Nieuwegein
-
Netherlands

Trial participating centre

University Hospital Southampton
Southampton
SO16 6YD
United Kingdom

Trial participating centre

Morriston Hospital
Swansea
SA6 6NL
United Kingdom

Trial participating centre

Oxford University Hospital
Oxford
OX3 9DU
United Kingdom

Trial participating centre

King’s College Hospital
London
SE5 9RS
United Kingdom

Trial participating centre

University Hospital Birmingham
Birmingham
B15 2TH
United Kingdom

Trial participating centre

The Freeman Hospital
Newcastle Upon Tyne
NE7 7DN
United Kingdom

Trial participating centre

Lübeck University Hospital
Lübeck
-
Germany

Trial participating centre

Universitätsklinikum Freiburg
Freiburg
-
Germany

Trial participating centre

Universitätsklinikum Erlangen
Erlangen
-
Germany

Trial participating centre

Heidelberg University Hospital
Heidelberg
-
Germany

Trial participating centre

Oslo University Hospital and Institute for Clinical Medicine
Oslo
-
Norway

Trial participating centre

Linköping University
Linköping
-
Sweden

Trial participating centre

Verona University Hospital
Verona
-
Italy

Trial participating centre

Universitá de Pisa
Pisa
-
Italy

Trial participating centre

Pederzoli Hospital
Peschiera
-
Italy

Trial participating centre

S. Orsola-Malpighi Hospital
Bologna
-
Italy

Trial participating centre

San Raffaele Hospital IRCCS
Milan
-
Italy

Trial participating centre

Niguarda Ca' Granda Hospital
Milan
-
Italy

Trial participating centre

Humanitas University Hospital
Milan
-
Italy

Trial participating centre

University Hospital Pavia
Pavia
-
Italy

Trial participating centre

Hospital of Beaujon
Beaujon
-
France

Trial participating centre

Centre Hospitalier Regional D’Orleans
Orleans
-
France

Trial participating centre

Hopital Saint Eloi
Montpellier
-
France

Trial participating centre

Institut Mutualiste Montsouris
Paris
-
France

Trial participating centre

Hospital del Mar
Barcelona
-
Spain

Trial participating centre

Hospital Clínic de Barcelona
Barcelona
-
Spain

Trial participating centre

Hospital Josep Trueta
Girona
-
Spain

Trial participating centre

Hospital Universitari Vall d'Hebron
Barcelona
-
Spain

Trial participating centre

Ghent University Hospital
Ghent
-
Belgium

Trial participating centre

University Medical Center Ljubljana
Ljubljana
-
Slovenia

Trial participating centre

Moscow Clinical Scientific Center
Moscow
-
Russian Federation

Trial participating centre

Virginia Mason Medical Center
Seattle
-
United States of America

Sponsor information

Organisation

University Hospital Southampton NHS Foundation Trust

Sponsor details

Mailpoint 18
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Organisation

Academic Medical Center

Sponsor details

Meibergdreef 9
Amsterdam
1105 AZ
Netherlands

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Charity

Funder name

Maag Lever Darm Stichting; Grant Codes: I 17-08

Alternative name(s)

Dutch Digestive Foundation, MLDS

Funding Body Type

private sector organisation

Funding Body Subtype

foundation

Location

Netherlands

Funder name

Academisch Medisch Centrum

Alternative name(s)

Academic Medical Center, AMC

Funding Body Type

private sector organisation

Funding Body Subtype

academic

Location

Netherlands

Results and Publications

Publication and dissemination plan

The results of this study will be submitted to a high-impact peer-reviewed medical journal regardless of the study outcome.

IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

01/12/2020

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes