Distal pancreatectomy, minimally invasive or open, for malignancy
| ISRCTN | ISRCTN44897265 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN44897265 |
| ClinicalTrials.gov number | NCT04483726 |
| Secondary identifying numbers | The United Kingdom: RHMGSU0230, CPMS ID 37581; The Netherlands: NL63299.018.17 |
- Submission date
- 16/04/2018
- Registration date
- 19/04/2018
- Last edited
- 28/05/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Surgery
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 Amsterdam UMC (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 2024
Who is funding the study?
1. The Dutch Digestive Foundation (The Netherlands)
2. Academic Medical Center, Amsterdam (The Netherlands)
3. Ethicon Endo-surgery Inc.
4. Medtronic
Who is the main contact?
1. Prof. Mohammed Abu Hilal
2. Prof. Marc Besselink
Contact information
Scientific
Southampton University Hospital NHS Foundation Trust
E level, Tremona Road
Southampton
SO16 6YD
United Kingdom
| Phone | + 44 (0)23 8079 6977/6994 |
|---|---|
| Abuhilal9@gmail.com |
Scientific
Academic Medical Center
Department of Surgery, room G04-196
PO Box 22660
Amsterdam
1100 DD
Netherlands
| Phone | +31 (0)20 5669 111 |
|---|---|
| m.g.besselink@amc.uva.nl |
Study information
| Study design | Multicenter; Randomized 1:1 ratio; Interventional; Patient-blinded |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | The Patient Information Sheet (English and Dutch) will be available on the following website: http://www.e-mips.org/diploma/ |
| Scientific title | Distal pancreatectomy, minimally invasive or open, for malignancy (DIPLOMA): a pan-European, randomized controlled, multicenter, patient blinded, non-inferiority trial |
| Study 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(s) | 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 Amsterdam UMC, location Academic Medical Center, 25/01/2018, ref: NL63299.018.17 For the following countries, separate ethical approvals have been obtained: Belgium, France, Germany, Italy, Norway, Russia, Slovenia, Spain, Sweden, Finland and the USA. |
| 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 |
| 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 study start date | 04/01/2018 |
| Overall study end date | 05/05/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 258 (129 per arm). The trialists expect every site to include 5-10 patients annually. |
| Total final enrolment | 258 |
| 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 exclusion criteria | Current exclusion criteria as of 19/05/2020: Patients that meet any of the following criteria will be excluded from participation in this study: 1. American Society of Anesthesiologists classification >3 2. A medical history of chronic pancreatitis (according to the M-ANNHEIM criteria) 3. Second malignancy necessitating resection during the same procedure 4. Distant metastases (M1) including involved distant lymph nodes 5. Tumor involvement or abutment of major vessels (celiac trunk*, mesenteric artery or portomesenteric vein); 6. Pregnancy 7. Participation in another study with interference of study outcomes *The celiac trunk should be 5mm clear from tumor Previous 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 | 07/05/2021 |
Locations
Countries of recruitment
- Belgium
- England
- France
- Germany
- Italy
- Netherlands
- Norway
- Russian Federation
- Slovenia
- Spain
- Sweden
- United Kingdom
- United States of America
- Wales
Study participating centres
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Netherlands
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Netherlands
-
Netherlands
-
Netherlands
-
Netherlands
-
Netherlands
SO16 6YD
United Kingdom
SA6 6NL
United Kingdom
OX3 9DU
United Kingdom
SE5 9RS
United Kingdom
B15 2TH
United Kingdom
NE7 7DN
United Kingdom
-
Germany
-
Germany
-
Germany
-
Germany
-
Norway
-
Sweden
-
Italy
-
Italy
-
Italy
-
Italy
-
Italy
-
Italy
-
Italy
-
Italy
-
France
-
France
-
France
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France
-
Spain
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Spain
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Spain
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Spain
-
Belgium
-
Slovenia
-
Russian Federation
-
United States of America
-
Italy
Sponsor information
Hospital/treatment centre
Mailpoint 18
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
England
United Kingdom
Hospital/treatment centre
Meibergdreef 9
Amsterdam
1105 AZ
Netherlands
| Website | https://www.amc.nl/web/Zorg.htm |
|---|---|
"ROR" |
https://ror.org/03t4gr691 |
Funders
Funder type
Charity
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Dutch Liver Foundation, Stomach Liver Bowel Foundation, MLDS
- Location
- Netherlands
Private sector organisation / Universities (academic only)
- Alternative name(s)
- Academic Medical Center, AMC
- Location
- Netherlands
Results and Publications
| Intention to publish date | 01/11/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| 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 plan | The data sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | 09/09/2021 | 13/09/2021 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Results article | 06/07/2023 | 17/07/2023 | Yes | No |
Editorial Notes
28/05/2024: The overall study end date was changed from 01/05/2024 to 05/05/2024. The intention to publish date was changed from 01/12/2022 to 01/11/2024.
08/04/2024: ClinicalTrials.gov number added.
17/07/2023: Publication reference added.
13/06/2022: The following changes were made to the trial record:
1. The ethics details were updated
2. The recruitment end date was changed from 01/05/2021 to 07/05/2021.
3. The intention to publish date was changed from 01/12/2021 to 01/12/2022.
4. The total final enrolment was added.
13/09/2021: Publication reference added.
09/07/2020: The trial contact details have been made publicly visible.
19/05/2020: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/05/2020 to 01/05/2021.
2. The overall end date was changed from 01/05/2023 to 01/05/2024.
3. The intention to publish date was changed from 01/12/2020 to 01/12/2021.
4. The plain English summary was updated to reflect these changes.
5. The ethics approval was updated.
6. The trial website was changed from http://www.e-mips.org/diploma to http://www.e-mips.org/diploma-trial
7. The exclusion criteria were changed.
8. The trial participating centre Poliambulanza Foundation Hospital was added.
06/08/2019: Internal review.
