The DRAGON 2 Trial (DRAGON 2)

October 29, 2024 updated by: Maastricht University

An International Multicenter Randomized Controlled Trial to Compare Combined Portal and Hepatic Vein Embolization (PVE/HVE) with PVE Alone in Patients with Colorectal Liver Cancer Metastases (CRLM) and a Small Future Liver Remnant (FLR)

In the randomized controlled DRAGON 2 trial study subjects will be randomized between two arms, PVE alone (control group) and PVE/HVE (interventional group).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Resection of liver metastases from colorectal cancer (CRLM) improves survival compared to chemotherapy alone and may lead to cure in up to 40% of patients. Extended liver resections are sometimes necessary to resect primarily unresectable/ potentially resectable (PU/PR) colorectal liver metastases. These resections are generally performed if the volume of the future liver remnant (FLR) comprises at least 30% of the total volume of the liver (without the volume of the metastases) or when liver function of the FLR on technetium-99m (99mTc) scintigraphy exceeds 2.67%/min/m2.

When this liver volume or function criterion is not met, a high chance of post-hepatectomy liver failure exists. To prevent this, the induction of liver regeneration between a two-stage hepatectomy is commonly performed.

The current standard procedure to induce regeneration is the embolization of the portal vein branches to the tumor carrying liver (PVE) to induce hypertrophy of the remaining part of the liver which will serve as the FLR. Recently, combined embolization of both portal and hepatic veins (PVE/HVE) has been described as a possible superior alternative to PVE, as it increases and accelerates hypertrophy of the FLR. PVE/HVE combines simultaneous embolization of the main portal vein branches into the tumor carrying liver and the hepatic vein draining this part of the liver. Preclinical studies in pigs, several retrospective studies, and the prospective DRAGON 1 interim analysis (n=60) have demonstrated the safety and feasibility of this novel technique. However, no international randomized controlled trial has been performed, in which combined PVE/HVE is compared with PVE

Study Type

Interventional

Enrollment (Estimated)

348

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

Study Contact Backup

Study Locations

  • Australia
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Recruiting
        • Monash Medical Centre
        • Contact:
          • Diederick De Boo, PhD
  • Austria
      • Vienna, Austria, 1100
        • Not yet recruiting
        • Social Medical Center, South
        • Contact:
          • Thomas Gruenberger, MD
        • Contact:
          • Tanja Friz, BSc
        • Contact:
          • Tony Padickakudy
        • Contact:
          • Tanja Fritz
        • Contact:
          • Ivan Baclija
  • Belgium
      • Liège, Belgium, 4000
        • Recruiting
        • CHU de Liège
        • Contact:
          • Celine Lambrecht
        • Contact:
          • Olivier Detry
        • Contact:
          • Olivier Detry, MD PhD
        • Contact:
          • Laurent Gérard, MD PhD
    • Bruxelles
      • Brussels, Bruxelles, Belgium, 1070
        • Recruiting
        • Hopital Erasme
        • Contact:
          • Valerio Lucidi, MD PhD
        • Contact:
          • Viviane van Laethem
        • Contact:
          • Illario Tancredi, MD PhD
    • Namen
      • Yvoir, Namen, Belgium, 5530
        • Recruiting
        • Chu-Ucl Namur Site Godinne
        • Contact:
          • Aelxandra Dili, MD PhD
        • Contact:
          • Claude Bertrand, MD PhD
        • Contact:
          • Alexandra Dili, MD PhD
        • Contact:
          • Jean- François De Wispelaere, MD PhD
    • Oost-Vlaanderen
      • Gent, Oost-Vlaanderen, Belgium, Gent (9000)
        • Recruiting
        • UZ Gent
        • Contact:
          • Luis Luis Abreu de Carvalho
        • Contact:
          • Luis Abreu de Carvalho
        • Contact:
          • Laurens Hermie
  • Canada
      • Montréal, Canada
        • Not yet recruiting
        • McGill University Health Center
        • Contact:
          • Jeniffer Kalil
        • Contact:
          • Peter Metrakos, Prof
        • Contact:
          • David Valenti, Md PhD
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4H5
        • Recruiting
        • Vancouver Coastal Health
        • Contact:
          • Maja Segedi
        • Contact:
          • Maya Segedi
    • Ontario
      • Hamilton, Ontario, Canada, ON L8V 5C2
        • Recruiting
        • Juravinski Hospital and Cancer Centre
        • Contact:
          • Leyo Ruo
      • Ottawa, Ontario, Canada, K1H 8L6
        • Recruiting
        • The Ottawa Hospital
        • Contact:
          • Guillaume Martel, MD
        • Contact:
          • Stephen Ryan, MD, PhD
        • Contact:
          • Aklile Workneh
      • Toronto, Ontario, Canada, M4N 3M5
        • Recruiting
        • Sunnybrook Hospital
        • Contact:
          • Paul Karanicolas
  • Italy
      • Milan, Italy
        • Recruiting
        • IRCCS San Raffaele Hospital
        • Contact:
          • Luca Aldrighetti, Prof
        • Contact:
          • Stephanie Steidler
        • Contact:
          • Luca Aldrighetti, Prof.
        • Contact:
          • Francesco De Cobelli, Prof.
        • Contact:
          • Francesca Ratti, Dr.
        • Contact:
          • Simone Gusmini, Dr.
        • Contact:
          • Salvatore Lamarca, Dr.
  • Netherlands
      • Breda, Netherlands
        • Not yet recruiting
        • Amphia
        • Contact:
          • Farshad Imani, MD PhD
        • Contact:
          • Paul Gobardhan, MD PhD
      • Eindhoven, Netherlands
        • Recruiting
        • Maxima Medisch Centrum
        • Contact:
          • Wouter Leclercq, MD PhD
        • Contact:
          • Wouter KG Leqlercq, MD PhD
        • Contact:
          • Laurens van Baardewijk, MD PhD
      • Groningen, Netherlands, 9713 GZ
        • Recruiting
        • University Medical Center Groningen
        • Contact:
          • Marieke T de Boer, MD PhD
        • Contact:
          • Jan T Bottema
        • Contact:
          • Koert P de Jong
        • Contact:
          • Reinhoud PH Bokkers
        • Contact:
          • Leanne van der Plas - Kemper
      • Utrecht, Netherlands
        • Recruiting
        • Universitair Medisch Centrum Utrecht
        • Contact:
          • Maarten LJ Smits, MD PhD
        • Contact:
          • Jeroen Hagendoorn, MD PhD
        • Contact:
          • Inne HM Borel Rinkes, Prof.
        • Contact:
          • Rutger CG Bruijnen, MD PhD
    • Limburg
      • Maastricht, Limburg, Netherlands, 6229 HX
        • Recruiting
        • Maastricht University Medical Center+
        • Contact:
        • Contact:
        • Contact:
          • Ronald M van Dam, MD, PhD
        • Contact:
          • Marc HA Bemelmans, MD, PhD
        • Contact:
          • Christiaan van der Leij, MD, PhD
        • Contact:
          • Remon Korenblik, MD
        • Contact:
          • Bram Olij, BCs
    • Noord-Holland
      • Amsterdam, Noord-Holland, Netherlands, 1105 AZ
        • Recruiting
        • Amsterdam UMC, location AMC
        • Contact:
          • Joris I Erdmann, MD PhD
        • Contact:
          • Otto M van Delden, MD PhD
    • Zuid-Holland
      • Rotterdam, Zuid-Holland, Netherlands, 3015
        • Not yet recruiting
        • Erasmus Medical Center
        • Contact:
          • Dirk J. Grünhagen, MD PhD
        • Contact:
          • Adriaan Moelker, MD PhD
        • Contact:
          • Drik J Grünhagen, MD PhD
  • Sweden
      • Linköping, Sweden, 581 85
        • Recruiting
        • Linkoping University Hospital
        • Contact:
          • Per Sandström, Prof.
        • Contact:
          • Bergthor Bjornsson, MD
        • Contact:
          • Margareta Ahle, MD
        • Contact:
          • Anna Lindhoff Larsson
      • Stockholm, Sweden, 14186
        • Recruiting
        • Karolinska University Hospital
        • Contact:
          • Ernesto Sparrelid, MD
        • Contact:
          • Martin Delle, MD
  • Switzerland
      • Winterthur, Switzerland, 8401
        • Recruiting
        • Kantonsspital Winterthur (KSW)
        • Contact:
          • Erik Schadde, MD
        • Contact:
          • Sabine Kern
        • Contact:
          • Chistoph A Binkert, MD
    • Basel-Stadt
      • Basel, Basel-Stadt, Switzerland, CH-4058
        • Recruiting
        • Claraspital & Clarunis University Hospital Basel
        • Contact:
          • Otto Kollmar, Prof.
        • Contact:
          • Bettina Woelnerhanssen
        • Contact:
          • Martin Hoffman, Prof.
        • Contact:
          • Gabriel Hess, Dr.
        • Contact:
          • Bettina Woelnershanssen
  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Recruiting
        • Yale New Haven Hospital
        • Contact:
          • Kevin Billingsley
        • Contact:
          • David Madoff

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

Description

Inclusion Criteria:

  • Patients with primarily unresectable/ potentially resectable CRLM with a FLR <30% (<40% in chemotherapy damaged livers)
  • Patients with non-resected primary CRC may be included if there is an intention to resect the CRC after the liver treatment (liver first approach) or simultaneously during one of the liver procedures.
  • Patients with resectable or ablatable lung or brain metastases can be included (statement about the resectability of these extrahepatic metastases by a tumor board needs to be available)
  • 18 Years and older
  • Men and women
  • Able to understand the trial and provide informed consent.

Exclusion Criteria:

  • Pregnant or lactating female.
  • Premenopausal females not able or willing to commit to oral contraception
  • Patients with prohibitive comorbidities, decision made by local team
  • Any patient with non-resectable or non-ablatable extrahepatic disease
  • Patients with hepatic malignancies other than CRLM
  • Progression of disease by RECIST criteria after cytoreduction chemotherapy
  • Complete response after conversion chemotherapy
  • Staging CT and (if indicated) CT/MRI brain that demonstrates non-resectable extrahepatic disease
  • The anatomy of the liver or manifestation of tumors in relation to the liver veins prohibits the use of combined PVE/HVE.

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: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Portal Vein Embolization (PVE) alone - (control arm)
Portal Vein Embolization (PVE) alone
Procedure: Embolization
Portal Vein embolization with Glue by a transhepatic approach vs. PVE and Hepatic Vein Occlusion with Vascular plugs via a transjugular or transfemoral approach in the same session as the PVE procedure
Experimental: Combined Portal and Hepatic Vein Embolization (PVE/HVE) - (interventional arm)
Procedure: Embolization
Portal Vein embolization with Glue by a transhepatic approach vs. PVE and Hepatic Vein Occlusion with Vascular plugs via a transjugular or transfemoral approach in the same session as the PVE procedure

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Volume sufficient for resection at week 3 after the embolization
Time Frame: 3 weeks
Volume sufficient for resection will be based on the first week or third week CT/MR Volumetry. Vauthey calculation for TLV will be used and the FLR volume will be measured centrally (objective panel)
3 weeks
5-year Overall Survival
Time Frame: 5 years
survival data will be recorded up to 5-years.
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Maastricht University

Investigators

  • Principal Investigator: Ronald M. van Dam, PhD, Maastricht Universitair Medisch Centrum

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)

April 1, 2022

Primary Completion (Estimated)

June 30, 2026

Study Completion (Estimated)

June 30, 2029

Study Registration Dates

First Submitted

February 1, 2022

First Submitted That Met QC Criteria

June 17, 2022

First Posted (Actual)

June 23, 2022

Study Record Updates

Last Update Posted (Estimated)

November 1, 2024

Last Update Submitted That Met QC Criteria

October 29, 2024

Last Verified

September 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL80303.068.22

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Upon reasonable request

IPD Sharing Time Frame

After publication

IPD Sharing Access Criteria

Proposal accepted by the DRAGON Collaborative Scientific Committee

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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