LIVACOR Trial: Minimally Invasive LIVer And Simultaneous COlorectal Resection (LIVACOR)

The LIVACOR - Trial is a European wide, randomized controlled, open-label, multicenter trial. Patients with synchronous colorectal liver metastases (CRLMs) and primary colorectal tumor are considered eligible and will be randomized between minimally invasive (MI) combined or staged colorectal resection (all colectomies, including high anterior resection) and liver resection of up to three segments.

Study Overview

• Status: Recruiting
• Conditions: Neoplasm Metastasis; Colorectal Neoplasms Malignant
• Intervention / Treatment: Procedure: Minimally invasive two-stage resection; Procedure: Minimally invasive simultaneous resection

• Study Type: Interventional
• Enrollment (Anticipated): 82
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jasper Sijberden, MD; Phone Number: 0031630150451; Email: jasper.sijberden@poliambulanza.it
• Study Contact Backup: Name: Professor Mohammed Abu Hilal, MD PhD; Email: abuhilal9@gmail.com

Study Locations

• Belgium
  • Limburg
    • Genk, Limburg, Belgium, 3600
      • Not yet recruiting
      • Ziekenhuis Oost-Limburg
      • Contact: Dennis Wicherts, PhD
      • Principal Investigator: Dennis Wicherts, PhD
      • Principal Investigator: Joep Knol, PhD
  • West Flanders
    • Kortrijk, West Flanders, Belgium, 8500
      • Recruiting
      • General Hospital Groeninge
      • Contact: Mathieu D'Hondt, PhD
      • Principal Investigator: Mathieu D'Hondt, PhD
      • Principal Investigator: Bart van Geluwe, PhD
• France
  • Île-de-France
    • Paris, Île-de-France, France, 92140
      • Not yet recruiting
      • Antoine-Beclere Hospital
      • Contact: Ibrahim Dagher, PhD
      • Principal Investigator: Ibrahim Dagher, PhD
      • Sub-Investigator: Panagiotis Lainas, PhD
• Germany
  • Saarland
    • Saarbrücken, Saarland, Germany, 66119
      • Recruiting
      • Klinikum Saarbrücken, Klinik für Allgemein-, Viszeral- und Thoraxchirurgie, Chirurgische Onkologie
      • Contact: Gregor Stavrou, MD
      • Principal Investigator: Gregor Stavrou, MD
• Italy
  • Calabria
    • Naples, Calabria, Italy, 80131
      • Not yet recruiting
      • Federico II University Hospital
      • Contact: Roberto Troisi, PhD
      • Principal Investigator: Roberto Troisi, PhD
      • Principal Investigator: Gaetano Luglio, PhD
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40124
      • Recruiting
      • Azienda USL di Bologna
      • Contact: Elio Jovine, PhD
      • Principal Investigator: Elio Jovine, PhD
      • Sub-Investigator: Michele Masetti, MD
      • Sub-Investigator: Simone Nicosia, MD
    • Modena, Emilia-Romagna, Italy, 41125
      • Not yet recruiting
      • Azienda Ospedaliero-Universitaria di Modena
      • Contact: Fabrizio di Benedetto, PhD
      • Principal Investigator: Fabrizio di Benedetto, PhD
    • Parma, Emilia-Romagna, Italy, 43126
      • Not yet recruiting
      • Parma University Hospital
      • Contact: Raffaele Dalla Valle, PhD
      • Principal Investigator: Raffaele Dalla Valle, PhD
      • Sub-Investigator: Mario Giuffrida, MD
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Recruiting
      • Fondazione Policlinico Universitario Agostino Gemelli Irccs
      • Contact: Felice Giuliante, PhD
      • Principal Investigator: Felice Giuliante, PhD
      • Principal Investigator: Roberto Persiani, PhD
  • Lombardy
    • Brescia, Lombardy, Italy, 25124
      • Recruiting
      • Fondazione Poliambulanza Istituto Ospedaliero
      • Contact: Mohammed Abu Hilal, PhD
      • Principal Investigator: Mohammed Abu Hilal, PhD
      • Sub-Investigator: Jasper Sijberden, MD
    • Milan, Lombardy, Italy, 20132
      • Not yet recruiting
      • San Raffaele University Hospital
      • Contact: Luca Aldrighetti, PhD
      • Principal Investigator: Luca Aldrighetti, PhD
  • Marche
    • Ancona, Marche, Italy, 60126
      • Not yet recruiting
      • Ospedali Riuniti
      • Contact: Marco Vivarelli, PhD
      • Principal Investigator: Marco Vivarelli, PhD
      • Principal Investigator: Mario Guerrieri, PhD
      • Sub-Investigator: Andrea Benedetti Cacciaguerra, MD
  • Piemonte
    • Turin, Piemonte, Italy, 10128
      • Not yet recruiting
      • Mauriziano Umberto I Hospital
      • Contact: Alessandro Ferrero, PhD
      • Principal Investigator: Alessandro Ferrero, PhD
      • Sub-Investigator: Paolo Massucco, MD
  • Veneto
    • Padova, Veneto, Italy, 35128
      • Recruiting
      • University Hospital Padova
      • Contact: Umberto Cillo, PhD
      • Principal Investigator: Umberto Cillo, PhD
      • Principal Investigator: Enrico Gringeri, PhD
      • Sub-Investigator: Jacopo Lanari, MD
• Luxembourg
  • Luxembourg, Luxembourg, L-1210
    • Recruiting
    • Centre Hospitalier du Luxembourg
    • Contact: Edoardo Rosso, MD
    • Principal Investigator: Edoardo Rosso, MD
• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229 HX
      • Not yet recruiting
      • Maastricht University Medical Center
      • Contact: Ronald van Dam, PhD
      • Principal Investigator: Ronald van Dam, PhD
      • Principal Investigator: Jarno Melenhorst, PhD
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1081 HV
      • Recruiting
      • Amsterdam UMC
      • Contact: Rutger-Jan Swijnenburg, PhD
      • Principal Investigator: Rutger-Jan Swijnenburg, PhD
• Norway
  • Østlandet
    • Oslo, Østlandet, Norway, N-0424
      • Recruiting
      • Oslo University Hospital
      • Contact: Bjørn Edwin, PhD
      • Principal Investigator: Bjørn Edwin, PhD
      • Principal Investigator: Sheraz Yaqub, PhD
      • Sub-Investigator: Asmund Fretland, PhD
• Russian Federation
  • Moscow Oblast
    • Moscow, Moscow Oblast, Russian Federation, 111123
      • Recruiting
      • Moscow Clinical Scientific Center
      • Contact: Mikhail Efanov, PhD
      • Principal Investigator: Mikhail Efanov, PhD
      • Principal Investigator: Mikhail Danilov, PhD
      • Sub-Investigator: Aslan Baychorov, PhD
• Spain
  • Catalonia
    • Barcelona, Catalonia, Spain, 08003
      • Recruiting
      • Hospital del Mar
      • Contact: Benedetto Ielpo, PhD
      • Principal Investigator: Benedetto Ielpo, PhD
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Not yet recruiting
      • University of Navarrra Hospital (Clinica Universitaria)
      • Contact: Fernando Rotellar, PhD
      • Principal Investigator: Fernando Rotellar, PhD
• United Kingdom
  • North West England
    • Manchester, North West England, United Kingdom, M13 9WL
      • Not yet recruiting
      • Manchester University NHS Foundation Trust
      • Contact: Aali Sheen, PhD
      • Principal Investigator: Aali Sheen, PhD
  • Northeast England
    • Newcastle, Northeast England, United Kingdom, NE1 4LP
      • Not yet recruiting
      • Newcastle-upon-Tyne Hospitals NHS Trust
      • Contact: Steve White, PhD
      • Principal Investigator: Steve White, PhD
  • Northwest England
    • Liverpool, Northwest England, United Kingdom, L7 8XP
      • Not yet recruiting
      • Liverpool University Hospitals NHS Foundation Trust
      • Contact: Rafael Díaz-Nieto, PhD
      • Principal Investigator: Rafael Díaz-Nieto, PhD
  • South East England
    • Southampton, South East England, United Kingdom, SO16 6YD
      • Not yet recruiting
      • University Hospital Southampton NHS Foundation Trust
      • Contact: John Primrose, PhD
      • Principal Investigator: John Primrose, PhD
      • Principal Investigator: Alex Mirnezami, PhD
  • Southeast England
    • London, Southeast England, United Kingdom, SE5 9RS
      • Not yet recruiting
      • King's College Hospital NHS Trust
      • Contact: Krishna Menon, PhD
      • Principal Investigator: Krishna Menon, PhD
      • Principal Investigator: Amyn Haji, MD
  • Southwest England
    • Plymouth, Southwest England, United Kingdom, PL6 8DH
      • Not yet recruiting
      • University Hospital Plymouth NHS Trust
      • Contact: Somaiah Aroori, PhD
      • Principal Investigator: Somaiah Aroori, PhD
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B15 1NT
      • Not yet recruiting
      • University Hospital Birmingham NHS Foundation Trust
      • Contact: Robert Sutcliffe, MD
      • Principal Investigator: Robert Sutcliffe, MD
      • Principal Investigator: Shazad Ashraf, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ≥ 18 years
• Diagnosed with primary CRC with resectable synchronous CRLMs (with or without neoadjuvant chemotherapy)*
• Elective indication for MI combined or staged colorectal resection (all colectomies, including high anterior resection) and liver resection of up to 3 segments with a maximum of 2 separate liver resections. The MI two-staged approach includes both the conventional strategy (first resection of primary colorectal tumor followed by liver resection for CRLMs) and liver-first strategy (first CRLMs resection followed by resection of colorectal primary tumor). Patients undergoing bilobar resections are eligible (if 3 or fewer segments are resected)
• BMI between and including 18-35

• Patients with American Society of Anesthesiologists (ASA) physical status I-III and the American College of Surgeons national surgical quality improvement project (ACS NSQIP) universal surgical risk score of ≤ 50% for serious complications

  • In case of neoadjuvant chemotherapy, time interval between last chemotherapy cycle and (first) surgery should be 4-6 weeks.

Exclusion Criteria:

• Inability to give (written) informed consent.
• Patients requiring a planned temporarily or permanent stoma after colorectal resection (all colectomies, including high anterior resection). Patients who will receive an unplanned stoma intraoperatively, will be analysed according to their initial treatment assignment.
• Patients requiring multivisceral colorectal resection (all colectomies, including high anterior resection).
• Indication for MI combined or staged low anterior resection, total mesorectal excision or abdominoperineal resection and liver resection of four or more segments (i.e., hemihepatectomy or more extensive resections).
• Patients with peritoneal metastases.
• Patients with ASA physical status IV-V and ACS NSQIP surgical risk score of > 50% for serious complications.
• Repeat open hepatectomy
• Surgical history of colorectal- or liver resection for neoplastic disease
• Surgical history of major or complicated open abdominal surgery
• Indication for concurrent thermal ablation
• Medical history of thermal ablation of liver for malignancy
• Unresectable extrahepatic metastases
• Pre-operatively reconstruction of vessels/bile ducts is deemed necessary

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Minimally invasive two-stage resection; Minimally invasive resection of the primary colorectal carcinoma and liver metastases in two stages. The liver metastases or the colorectal carcinoma can be resected during the first surgical procedure.	Procedure: Minimally invasive two-stage resection; Two minimally invasive surgical procedures wherein the primary colorectal carcinoma and the liver metastases are removed; Other Names: Minimally invasive sequential resection
Experimental: Minimally invasive simultaneous resection; Minimally invasive resection of both the primary colorectal carcinoma and the liver metastases in one procedure.	Procedure: Minimally invasive simultaneous resection; One minimally invasive surgical procedure wherein both the primary colorectal carcinoma and the liver metastases are removed.; Other Names: Minimally invasive combined resection; Minimally invasive synchronous resection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to functional recovery	A patient is considered functionally recovered from a surgical procedure when several pre-specified criteria have been met.	Expected average of 4 to 12 days postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0 resection margin	Proportion of patients in whom a microscopically radical resection of both the primary colorectal carcinoma and the liver metastases was performed.	30 days postoperatively
Length of hospital stay	The length of hospital stay for the surgical procedure(s)	30 days postoperatively
Activity tracking using Fitbit™	A patient's functional recovery will also be assessed using the Fitbit smartwatch.	14 days pre-operatively and 60 days postoperatively
Intraoperative blood loss	Intraoperative blood loss in milliliters	During the surgical procedure
Operative time	Operative time in minutes	Operative time from incision until last suture
Morbidity	Morbidity related to the surgical procedure(s)	90-days postoperatively
Postoperative bile leakage	Bile leakage occurring after the liver resection	90-days postoperatively
Postoperative anastomotic leakage	Anastomotic leakage occurring after the colorectal resection	90-days postoperatively
Conversion to open surgery	Intra-operative conversion to an open or hand-assisted procedure	During the surgical procedure
Readmission rate	Proportion of patients who is unexpectedly readmitted after the surgical procedure(s)	90-days postoperatively
Health-Related Quality of Life	The physical, social and emotional well-being of the patient; assessed using the EuroQol 5d and European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 instruments.	1 year postoperatively
Reasons for delay of discharge after functional recovery	All reasons that may cause delay in discharge after the patient has recovered functionally, such as administrative reasons, patient confidence, logistics problems, etc.	30 days postoperatively
Hospital and societal costs	All costs that are associated with the operation, including in-hospital costs and out of hospital costs, such as home care, work absence, etc.	1 year postoperatively
Three and five-year recurrence free survival	The proportion of patients which is free of recurrence of the malignant disease after resection of both the primary colorectal carcinoma and the liver metastases.	5 years postoperatively
Three and five-year overall survival	The proportion of patients which is alive after resection of both the primary colorectal carcinoma and the liver metastases.	5 years postoperatively

Collaborators and Investigators

• Sponsor: Fondazione Poliambulanza Istituto Ospedaliero
• Collaborators: Assistance Publique - Hôpitaux de Paris; King's College Hospital NHS Trust; Fondazione Policlinico Universitario Agostino Gemelli IRCCS; Oslo University Hospital; Federico II University; Maastricht University Medical Center; Azienda Usl di Bologna; Liverpool University Hospitals NHS Foundation Trust; University Hospital Birmingham NHS Foundation Trust; General Hospital Groeninge; Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); Manchester University NHS Foundation Trust; University Hospital Southampton NHS Foundation Trust; Ziekenhuis Oost-Limburg; Newcastle-upon-Tyne Hospitals NHS Trust; Hospital del Mar; University Hospital Plymouth NHS Trust; Azienda Ospedaliero-Universitaria di Modena; Parma University Hospital; University Hospital Padova; Klinikum Saarbrücken, Klinik für Allgemein-, Viszeral- und Thoraxchirurgie, Chirurgische Onkologie; Centre Hospitalier du Luxembourg; San Raffaele University Hospital, Italy; Moscow Clinical Scientific Center; University of Navarrra Hospital (Clinica Universitaria); Ospedali Riuniti Ancona; Mauriziano Umberto I Hospital
• Investigators: Study Chair: Professor Mohammed Abu Hilal, MD PhD, Fondazione Poliambulanza Istituto Ospedaliero

Publications and helpful links

General Publications

• van der Poel MJ, Tanis PJ, Marsman HA, Rijken AM, Gertsen EC, Ovaere S, Gerhards MF, Besselink MG, D'Hondt M, Gobardhan PD. Laparoscopic combined resection of liver metastases and colorectal cancer: a multicenter, case-matched study using propensity scores. Surg Endosc. 2019 Apr;33(4):1124-1130. doi: 10.1007/s00464-018-6371-1. Epub 2018 Aug 1.
• Pan L, Tong C, Fu S, Fang J, Gu Q, Wang S, Jiang Z, Juengpanich S, Cai X. Laparoscopic procedure is associated with lower morbidity for simultaneous resection of colorectal cancer and liver metastases: an updated meta-analysis. World J Surg Oncol. 2020 Sep 21;18(1):251. doi: 10.1186/s12957-020-02018-z.
• Boudjema K, Locher C, Sabbagh C, Ortega-Deballon P, Heyd B, Bachellier P, Metairie S, Paye F, Bourlier P, Adam R, Merdrignac A, Tual C, Le Pabic E, Sulpice L, Meunier B, Regimbeau JM, Bellissant E; METASYNC Study group. Simultaneous Versus Delayed Resection for Initially Resectable Synchronous Colorectal Cancer Liver Metastases: A Prospective, Open-label, Randomized, Controlled Trial. Ann Surg. 2021 Jan 1;273(1):49-56. doi: 10.1097/SLA.0000000000003848.
• Gavriilidis P, Sutcliffe RP, Hodson J, Marudanayagam R, Isaac J, Azoulay D, Roberts KJ. Simultaneous versus delayed hepatectomy for synchronous colorectal liver metastases: a systematic review and meta-analysis. HPB (Oxford). 2018 Jan;20(1):11-19. doi: 10.1016/j.hpb.2017.08.008. Epub 2017 Sep 7.

Study record dates

Study Major Dates

• Study Start (Actual): August 6, 2021
• Primary Completion (Anticipated): September 1, 2023
• Study Completion (Anticipated): September 1, 2024

Study Registration Dates

• First Submitted: November 5, 2021
• First Submitted That Met QC Criteria: November 17, 2021
• First Posted (Actual): November 30, 2021

Study Record Updates

• Last Update Posted (Actual): July 25, 2022
• Last Update Submitted That Met QC Criteria: July 22, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Neoplasms; Colorectal Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: NP3969

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No