Clinical trial NCT04400357: Robotic Versus Open Pancreaticoduodenectomy for Pancreatic and Periampullary Tumors
Official title: Robotic Versus Open Pancreaticoduodenectomy for Pancreatic and Periampullary Tumors: A Multicenter Phase III Non-Inferiority Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Pancreatic Adenocarcinoma
Pancreatic Cysts
Pancreatic Endocrine Tumors
Chronic Pancreatitis
Cholangiocarcinoma, Extrahepatic
Ampullary Adenocarcinoma
Duodenal Adenocarcinoma
Keywords: pancreaticoduodenectomy
Whipple
robotic
daVinci
pancreatic cancer
outcomes
pancreatectomy
functional recovery
complications
recurrence
circulating tumor DNA
perioperative inflammation
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
Collaborators: name: Intuitive Surgical
First posted: 2020-05-22
Enrollment: 244
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This multicenter randomized trial aims to primarily assess and compare the functional recovery of patients who undergo open versus robotic pancreaticoduodenectomy for benign and malignant lesions of the head of the pancreas.

Detailed description: The PORTAL trial is a Phase 3 multicenter non-inferiority randomized controlled trial that aims to address the question of feasibility and efficacy of the robotic minimally invasive approach in pancreaticoduodenectomy.

In the past 10 years there has been an increasing number of retrospective series from major centers for pancreatic surgery worldwide, that demonstrate similar and occasionally improved postoperative outcomes in patients who undergo a robotic pancreaticoduodenectomy (Whipple). The benefits of this minimally invasive approach appear to be decreased intraoperative estimated blood loss, lower postoperative pain levels and smaller length of hospital stay, whereas postoperative complications rates are comparable with the standard open approach.

This trial is conducted in multiple major centers for pancreatic surgery (open and robotic) in China and aims to address these questions in a prospective fashion. All eligible patients who present to these centers within the study period will be randomized in a 1:1 ratio to either of the two arms (open vs. robotic). Patients enrolled in the study will be blinded regarding the type of the procedure by application of identical wound dressings at the trocar sites and the open incision. Patients will be followed up closely and will be evaluated routinely for quality of life parameters for a period of at least 2 years postoperatively. Additionally, patients who undergo surgery in either arm for pancreatic adenocarcinoma will also be evaluated for time to adjuvant chemotherapy postoperatively, as well as recurrence and survival data.

Eligibility criteria: Inclusion Criteria:

* Patients with an indication for elective pancreaticoduodenectomy for malignant, premalignant, and symptomatic benign disease in the pancreatic and periampullary region
* Performance status of 0/1 (assessed based on comorbidities using the Karnofsky score and Malnutrition Universal Screening Tool score among others, especially for patients with malignant disease)
* Imaging with computed tomography and/or MRI pancreas performed within 8 weeks for benign and 4 weeks for malignant disease; for the latter tumor staging with MRI liver, CT chest, and Cancer Antigen 19-9 is also mandatory.

Exclusion Criteria:

* Body mass index \> 35 kg/m2
* Pregnancy
* Previous history of major abdominal surgery
* Requirement for multivisceral resection (additional surgical resection)
* Preoperative chemotherapy and/or radiotherapy (for patients with pancreatic adenocarcinoma)
* Involvement of major regional vessels by the tumor (portal and superior mesenteric vein, superior mesenteric artery, hepatic artery, celiac artery) as defined by the borderline resectable and locally advanced nomenclature

Primary outcomes:
measure: Time to functional recovery postoperatively
timeFrame: From date of surgery to date of functional recovery as described, assessed up to 90 days.
measure: Percentage of patients with pancreatic adenocarcinoma who achieve administration of adjuvant chemotherapy at 8 weeks postoperatively
timeFrame: Postoperative Day 1 to Day 56
Secondary outcomes:
measure: Intraoperative blood loss
timeFrame: During surgery
measure: Operative time
timeFrame: During surgery
measure: Postoperative complication rates and associated interventions
timeFrame: Postoperative Day 1 to Day 30
measure: Postoperative mortality
timeFrame: Postoperative Day 1 to Day 90
measure: Quality of life measurements
timeFrame: Postoperative Day 1 to Day 90
measure: Margin resection status (R) in patients with pancreatic adenocarcinoma
timeFrame: During surgery
measure: Differences in locoregional lymphadenectomy in patients with pancreatic adenocarcinoma
timeFrame: During surgery
measure: Postoperative recurrence in patients with pancreatic adenocarcinoma
timeFrame: Postoperative Day 1 up to 5 years after surgery
measure: Postoperative survival in patients with pancreatic adenocarcinoma
timeFrame: Postoperative Day 1 up to 5 years after surgery
measure: Perioperative costs
timeFrame: Postoperative Day 1 to Day 90
measure: Effect of operative approach on circulating biomarkers in the postoperative setting
timeFrame: Postoperative Day 1 to Day 30
measure: Comparison of perioperative inflammatory response (C-reactive protein)
timeFrame: Day of surgery to Postoperative Day 7
measure: Comparison of perioperative inflammatory response (Neutrophil-to-Lymphocyte ratio)
timeFrame: Day of surgery to Postoperative Day 7
measure: Comparison of perioperative inflammatory response (Interleukin-6)
timeFrame: Day of surgery to Postoperative Day 7
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ruijin Hospital Shanghai Jiaotong University School of Medicine
state: Shanghai
Study officials:
affiliation: Ruijin Hospital
name: Baiyong Shen, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nassour I, Winters SB, Hoehn R, Tohme S, Adam MA, Bartlett DL, Lee KK, Paniccia A, Zureikat AH. Long-term oncologic outcomes of robotic and open pancreatectomy in a national cohort of pancreatic adenocarcinoma. J Surg Oncol. 2020 Aug;122(2):234-242. doi: 10.1002/jso.25958. Epub 2020 Apr 29.
citation: Shi Y, Jin J, Qiu W, Weng Y, Wang J, Zhao S, Huo Z, Qin K, Wang Y, Chen H, Deng X, Peng C, Shen B. Short-term Outcomes After Robot-Assisted vs Open Pancreaticoduodenectomy After the Learning Curve. JAMA Surg. 2020 May 1;155(5):389-394. doi: 10.1001/jamasurg.2020.0021.
citation: Podda M, Gerardi C, Di Saverio S, Marino MV, Davies RJ, Pellino G, Pisanu A. Robotic-assisted versus open pancreaticoduodenectomy for patients with benign and malignant periampullary disease: a systematic review and meta-analysis of short-term outcomes. Surg Endosc. 2020 Jun;34(6):2390-2409. doi: 10.1007/s00464-020-07460-4. Epub 2020 Feb 18.
citation: Zureikat AH, Beane JD, Zenati MS, Al Abbas AI, Boone BA, Moser AJ, Bartlett DL, Hogg ME, Zeh HJ 3rd. 500 Minimally Invasive Robotic Pancreatoduodenectomies: One Decade of Optimizing Performance. Ann Surg. 2021 May 1;273(5):966-972. doi: 10.1097/SLA.0000000000003550.
citation: Girgis MD, Zenati MS, King JC, Hamad A, Zureikat AH, Zeh HJ, Hogg ME. Oncologic Outcomes After Robotic Pancreatic Resections Are Not Inferior to Open Surgery. Ann Surg. 2021 Sep 1;274(3):e262-e268. doi: 10.1097/SLA.0000000000003615.
citation: Shi Y, Wang W, Qiu W, Zhao S, Wang J, Weng Y, Huo Z, Jin J, Wang Y, Deng X, Shen B, Peng C. Learning Curve From 450 Cases of Robot-Assisted Pancreaticoduocectomy in a High-Volume Pancreatic Center: Optimization of Operative Procedure and a Retrospective Study. Ann Surg. 2021 Dec 1;274(6):e1277-e1283. doi: 10.1097/SLA.0000000000003664.
citation: Zhao W, Liu C, Li S, Geng D, Feng Y, Sun M. Safety and efficacy for robot-assisted versus open pancreaticoduodenectomy and distal pancreatectomy: A systematic review and meta-analysis. Surg Oncol. 2018 Sep;27(3):468-478. doi: 10.1016/j.suronc.2018.06.001. Epub 2018 Jun 4.
citation: McMillan MT, Zureikat AH, Hogg ME, Kowalsky SJ, Zeh HJ, Sprys MH, Vollmer CM Jr. A Propensity Score-Matched Analysis of Robotic vs Open Pancreatoduodenectomy on Incidence of Pancreatic Fistula. JAMA Surg. 2017 Apr 1;152(4):327-335. doi: 10.1001/jamasurg.2016.4755.
citation: Zureikat AH, Postlewait LM, Liu Y, Gillespie TW, Weber SM, Abbott DE, Ahmad SA, Maithel SK, Hogg ME, Zenati M, Cho CS, Salem A, Xia B, Steve J, Nguyen TK, Keshava HB, Chalikonda S, Walsh RM, Talamonti MS, Stocker SJ, Bentrem DJ, Lumpkin S, Kim HJ, Zeh HJ 3rd, Kooby DA. A Multi-institutional Comparison of Perioperative Outcomes of Robotic and Open Pancreaticoduodenectomy. Ann Surg. 2016 Oct;264(4):640-9. doi: 10.1097/SLA.0000000000001869.
citation: Jin J, Shi Y, Chen M, Qian J, Qin K, Wang Z, Chen W, Jin W, Lu F, Li Z, Wu Z, Jian L, Han B, Liang X, Sun C, Wu Z, Mou Y, Yin X, Huang H, Chen H, Gemenetzis G, Deng X, Peng C, Shen B. Robotic versus Open Pancreatoduodenectomy for Pancreatic and Periampullary Tumors (PORTAL): a study protocol for a multicenter phase III non-inferiority randomized controlled trial. Trials. 2021 Dec 27;22(1):954. doi: 10.1186/s13063-021-05939-6.