DRAGON 1- Training, Accreditation, Implementation and Safety Evaluation of Combined PVE/HVE (DRAGON)

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ClinicalTrials.gov Identifier: NCT04272931

Recruitment Status : Recruiting

First Posted : February 17, 2020

Last Update Posted : July 12, 2022

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Sponsor:

Collaborator:

Koningin Wilhelmina Fonds

Information provided by (Responsible Party):

Maastricht University

Study Description

Brief Summary:

Brief Summary: Some colorectal liver metastases can only be resected after inducing liver regeneration by portal vein embolization (PVE) to increase size function of the future liver remnant (FLR). While PVE is standard, embolization of portal vein and hepatic veins (PVE/HVE) on one side of the liver may faster and more extensive liver size and function growth. PVE/HVE is a novel procedure and requires a safety and feasibility evaluation in a pretrial (DRAGON1) to then be compared in a randomized controlled trial (RCT) to PVE (DRAGON 2).

Condition or disease	Intervention/treatment	Phase
Colorectal Cancer Liver Metastases	Procedure: Portal and Hepatic Vein Embolization	Not Applicable

Detailed Description:

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. Surgical resectability is limited by location of metastases and by FLR size and function. Commonly, the volume of the future liver remnant (FLR) should be at least 30% of the functional FLR volume. If this volume criterion is not met, the induction of liver regeneration between a two-stage hepatectomy is performed at many centers, with the aim to render patients resectable and reduce the risk of post hepatectomy liver failure. Gold standard to induce regeneration is the embolization of the portal vein branches to the tumor carrying liver (PVE) to induce regeneration of the FLR. Recently, combined embolization of both portal and hepatic veins (PVE/HVE) has been described as an alternative to portal vein embolization because it accelerates and increases growth of the FLR. PVE/HVE combines simultaneous embolization of the portal main branches into the tumor bearing liver and the hepatic vein draining them. The tissue in the part of the liver treated with PVE/HVE stays viable because the hepatic artery continues to supplies the liver deprived of portal and hepatic veins. Preclinical studies in pigs have demonstrated feasibility of this method and human case series show accelerated and increased liver growth. No multi-center evaluation has been performed so far. DRAGON 1 is an international, prospective, multi-center trial to test enrolment capacity of participants and safety of portal and hepatic vein embolization (PVE/HVE). DRAGON 1 will form the basis of the RCT DRAGON 2 to compare PVE with PVE/HV. DRAGON 2 is expected to start in 2021.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	125 participants
Allocation:	N/A
Intervention Model:	Single Group Assignment
Intervention Model Description:	Multicenter, international, prospective, multi-center trial to test enrolment capacity of participants and safety of Portal and Hepatic Vein Embolization (PVE/HVE): DRAGON 1 will form the basis of a planned subsequent trial ("DRAGON 2") that will compare PVE with PVE/HVE. In DRAGON 1 every center has to demonstrate the ability to enroll 3 patients in 12 months safely
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	DRAGON 1- Training, Accreditation, Implementation and Safety Evaluation of Portal and Hepatic Vein Embolization to Accelerate Future Liver Remnant (FLR) Hypertrophy
Actual Study Start Date :	May 8, 2020
Estimated Primary Completion Date :	October 1, 2022
Estimated Study Completion Date :	October 1, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Portal and Hepatic Vein Embolization 3 patients per center over one year approximately 90 patients in total. Patients will undergo portal vein and hepatic vein embolization instead of only portal vein embolization.	Procedure: Portal and Hepatic Vein Embolization Procedure/Surgery: Combined portal vein embolization and hepatic vein embolization (PVE/HVE) • All techniques of PVE allowed (ipsi-lateral, contra-lateral, trans-splenic, all embolization agents except for ethanol alone) • All modifications of HVE allowed (venous occlusion umbrellas; trans-jugular, trans-hepatic, no use of vein glue to avoid lung embolization; staged approach allowed, but first PVE, then HVE and within 48 hours) Other Names: Liver venous deprivation (LVD) Double embolization

Arm

Intervention/treatment

Experimental: Portal and Hepatic Vein Embolization

3 patients per center over one year approximately 90 patients in total. Patients will undergo portal vein and hepatic vein embolization instead of only portal vein embolization.

Procedure: Portal and Hepatic Vein Embolization

Procedure/Surgery: Combined portal vein embolization and hepatic vein embolization (PVE/HVE) • All techniques of PVE allowed (ipsi-lateral, contra-lateral, trans-splenic, all embolization agents except for ethanol alone) • All modifications of HVE allowed (venous occlusion umbrellas; trans-jugular, trans-hepatic, no use of vein glue to avoid lung embolization; staged approach allowed, but first PVE, then HVE and within 48 hours)

Other Names:

Liver venous deprivation (LVD)
Double embolization

Outcome Measures

Primary Outcome Measures :

Ability of each center to enroll 3 patients in 12 months without mortality due to the intervention. [ Time Frame: 1 year/ 90 day mortality ]
Ability of each center to enroll 3 patients for PVE/HVE in 12 months safely and perform the procedure including the liver resection without 90-day mortality after resection due to complications. If this goal is achieved center will be enrolled in DRAGON 2.

Secondary Outcome Measures :

Efficacy assessment: standardized future liver remnant volume [ Time Frame: 6 weeks ]
Increased of standardized future liver remnant volume between initial imaging and imaging at 1 week, 3 weeks, 6 weeks, degree of hypertrophy based on standard future liver remnant volume, kinetic growth
Feasibility assessment: resection rate [ Time Frame: 1 year follow up ]
ion of patients proceeding to complete resection (=resection rate)
Mortality assessment [ Time Frame: 90 days ]
90-mortality after resection
Overall survival after PVE/HVE [ Time Frame: 1 year follow up ]
Overall survival
Oncological effectiveness of PVE/HVE [ Time Frame: 1 year ]
Disease-free survival after 1 year
General complication assessment [ Time Frame: 90 days ]
90-day complications, general (Clavien-Dindo)
Liver specific complication assessment [ Time Frame: 90 days ]
90-day complications, liver specific (FABIB-classification)

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with primarily unresectable/potentially resectable CRLM after conversion chemotherapy with a FLR <30% in normal livers, or 40% in livers chemotherapy damaged livers.
18 years and older
Patients up to ECOG 3 (not more than 50% bedbound)
Patients with non-resected primary colorectal cancer (CRC) may be included if and only if there is an intent to remove the CRC after the liver treatment (liver first approach)
Staging CT chest and (if symptomatic) CT/MRI excludes unresectable extrahepatic disease, while metastatic disease that may be cured in the future, is included.
Patients with resectable lung metastases or lung metastases that and be ablated can be included only after statement about resectability/ablatability by tumor board
Patients have to be to understand the trial and provide informed consent.

Exclusion Criteria:

Patients with extrahepatic disease other than lung metastases
Patients with metastatic disease to the lung that cannot be ablated or resected will be excluded
Patients with intrahepatic Cholangiocarcinoma (IHCC)
Patients with Perihilar Cholangiocarcinoma (PHCC)
Patients with Hepatocellular Carcinoma (HCC)
Pregnant or lactating women will not be eligible
Potential to get pregnant has to be excluded (obligatory contraception etc.)
Progression by modified RECIST criteria on cross-sectional imaging after conversion chemotherapy is an exclusion criterion. Complete response in cross-sectional imaging after conversion chemotherapy.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04272931

Contacts

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Contact: Remon Korenblik, MD	+31 637297507	remon.korenblik@mumc.nl
Contact: Ronald M. van Dam, MD, PhD		r.van.dam@mumc.nl

Locations

Show 42 study locations

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United States, Connecticut
Yale School of Medicine	Recruiting
New Haven, Connecticut, United States, 06510
Contact: David C Madoff, MD PhD
Contact: Kristin DeFrancesco
Principal Investigator: David C Madoff, MD PhD
Sub-Investigator: Kristin DeFrancesco
United States, Illinois
Rush University Medical Center	Recruiting
Chicago, Illinois, United States, 60612
Contact: Erik Schadde, MD PhD
Contact: Jordan C Tasse, MD PhD
Principal Investigator: Erik Schadde, MD PhD
Principal Investigator: Jordan C Tasse, MD PhD
Sub-Investigator: Sam G Pappas, MD PhD
Sub-Investigator: Bulent Arslan, MD PhD
Sub-Investigator: Ashiq Masood, MD PhD
Sub-Investigator: Karl Villanueva
Sub-Investigator: Karie Karolinski
United States, New York
Memorial Sloan Kettering Cancer Center	Recruiting
New York, New York, United States, 10065
Contact: T. Peter Kingham, MD PhD
Contact: Juan C Camacho, MD PhD
Principal Investigator: T. Peter Kingham, MD PhD
Principal Investigator: Juan C Camacho, MD PhD
Sub-Investigator: Alicia N Lashley
Australia, New South Wales
Royal Prince Alfred Hospital	Recruiting
Camperdown, New South Wales, Australia, NSW 2050
Contact: Oliver Fisher, MD PhD
Contact: Christopher Rogan, MD PhD
Principal Investigator: Oliver Fisher, MD PhD
Principal Investigator: Christopher Rogan, MD PhD
Sub-Investigator: Michael Crawford, MD PhD
Sub-Investigator: Daniel Steffens, MD PhD
Australia, Victoria
Monash Health, Clayton	Recruiting
Clayton, Victoria, Australia, VIC 3168
Contact: Diederick de Boo, MD PhD
Principal Investigator: Daniel de Boo, MD PhD
Principal Investigator: Daniel Croagh, MD PhD
Austria
Social Medical Center, South	Completed
Vienna, Austria, 1100
Belgium
Hôpital Erasme	Recruiting
Brussels, Bruxelles, Belgium, 1070
Contact: Valerio Lucidi, MD PhD
Contact: Viviane van Laethem
Principal Investigator: Valerio Lucidi, MD PhD
Principal Investigator: Illario Tancredi, MD PhD
Sub-Investigator: viviane van Laethem
CHU-UCL Namur site Godinne	Recruiting
Yvoir, Namen, Belgium, 5530
Contact: Aelxandra Dili, MD PhD
Contact: Claude Bertrand, MD PhD
Principal Investigator: Alexandra Dili, MD PhD
Principal Investigator: Jean- François De Wispelaere, MD PhD
Sub-Investigator: Claude Bertrand, MD PhD
CHU de Liège	Recruiting
Liège, Belgium, 4000
Contact: Celine Lambrecht
Contact: Olivier Detry
Sub-Investigator: Celine Lambrecht
Principal Investigator: Olivier Detry, MD PhD
Principal Investigator: Laurent Gérard, MD PhD
Canada, Ontario
The Ottawa Hospital	Recruiting
Ottawa, Ontario, Canada, k1H 8L6
Contact: Guillaume Martel, MD
Contact: Stephen Ryan, MD, PhD
Principal Investigator: Guillaume Martel, MD
Principal Investigator: Stephen Ryan, MD, PhD
Sub-Investigator: Aklile Workneh
Canada
McGill University Health Center	Recruiting
Montréal, Canada
Contact: Jeniffer Kalil
Principal Investigator: Peter Metrakos, Prof
Principal Investigator: David Valenti, Md PhD
Germany
Klinikum Saarbrücken gGmbH	Recruiting
Saarbrücken, Saarland, Germany, 66119
Contact: habil. Gregor A Stavrou, MD PhD
Contact: Elmar Spüntrup, Prof.dr.
Principal Investigator: habil. Gregor A Stavrou, MD PhD
Principal Investigator: Elmar Spüntrup, Prof. dr.
University Hospital Halle (Saale)	Recruiting
Halle (Saale), Saksen-Anhalt, Germany, 06120
Contact: Ulrich Ronellenfitsch, MD, Dr. med
Contact: Jörg Kleeff, MD, Dr. med
Principal Investigator: Ulrich Ronellenfitsch, MD Dr. Med
Sub-Investigator: Jörg Kleeff, MD Dr. Med
Principal Investigator: Walter A Wohlgemuth, MD Dr. Med
Sub-Investigator: Zhanna Svatko
Frankfurt University Hospital	Completed
Frankfurt, Germany
Italy
Policlinico Sant'Orsola-Malpighi	Recruiting
Bologna, Italy, 40138
Contact: Matteo Serenari, MD phD
Contact: Alberta Capelli, MD phD
Principal Investigator: Matteo Serenari, MD phD
Principal Investigator: Alberta Capelli, MD phD
Fondazione Poliambulanza	Recruiting
Brescia, Italy, 25124
Contact: Mohammad Abu Hilal, MD PhD
Contact: Claudio Salemmi, MD PhD
Principal Investigator: Mohammad Abu Hilal, MD PhD
Principal Investigator: Claudio Salemmi, MD PhD
IRCCS San Raffaele Hospital	Recruiting
Milan, Italy
Contact: Luca Aldrighetti, Prof
Contact: Stephanie Steidler
Principal Investigator: Luca Aldrighetti, Prof.
Principal Investigator: Francesco De Cobelli, Prof.
Sub-Investigator: Francesca Ratti, Dr.
Sub-Investigator: Simone Gusmini, Dr.
Sub-Investigator: Salvatore Lamarca, Dr.
Sub-Investigator: Stephanie Steidler
Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Recruiting
Roma, Italy, 00168 Roma
Contact: Felice Giuliante, MD PhD
Contact: Roberto Iezzie, MD PhD
Principal Investigator: Felice Giuliante, MD PhD
Principal Investigator: Roberto Iezzie, MD PhD
Netherlands
Maastricht University Medical Center+	Completed
Maastricht, Limburg, Netherlands, 6229 HX
Amsterdam UMC, location AMC	Recruiting
Amsterdam, Noord-Holland, Netherlands, 1105 AZ
Contact: Joris I Erdmann, MD PhD
Contact: Otto M van Delden, MD PhD
Principal Investigator: Joris I Erdmann, MD PhD
Principal Investigator: Otto M van Delden, MD PhD
Erasmus Medical Center	Completed
Rotterdam, Zuid-Holland, Netherlands, 3015
Amsterdam Medical Centers, Location VUmc	Recruiting
Amsterdam, Netherlands, 1081HV
Contact: Martijn R Meijerink, MD PhD
Contact: Evelien Schouten
Principal Investigator: Martijn R Meijerink, MD PhD
Principal Investigator: Geert Kazemier, Prof.
Sub-Investigator: Jan de Vries, MD PhD
Sub-Investigator: Evelien Schouten
Amphia	Recruiting
Breda, Netherlands
Contact: Farshad Imani, MD PhD
Principal Investigator: Farshad Imani, MD PhD
Principal Investigator: Paul Gobardhan, MD PhD
Maxima Medisch Centrum	Recruiting
Eindhoven, Netherlands
Contact: Wouter Leclercq, MD PhD
Principal Investigator: Wouter KG Leqlercq, MD PhD
Principal Investigator: Laurens van Baardewijk, MD PhD
University Medical Center Groningen	Recruiting
Groningen, Netherlands, 9713 GZ
Contact: Marieke T de Boer, MD PhD
Contact: Jan T Bottema
Principal Investigator: Marieke T de Boer, MD PhD
Principal Investigator: Koert P de Jong
Principal Investigator: Reinhoud PH Bokkers
Sub-Investigator: Jan T Bottema
Sub-Investigator: Leanne van der Plas - Kemper
Universitair Medisch Centrum Utrecht	Recruiting
Utrecht, Netherlands
Contact: Maarten LJ Smits, MD PhD
Principal Investigator: Maarten LJ Smits, MD PhD
Sub-Investigator: Jeroen Hagendoorn, MD PhD
Sub-Investigator: Inne HM Borel Rinkes, Prof.
Sub-Investigator: Rutger CG Bruijnen, MD PhD
Norway
Oslo University Hospital	Completed
Oslo, Norway, 0450 Oslo
Spain
University Hospital Germans Trias I Pujol	Completed
Badalona, Barcelona, Spain, 08916 Badalona
University Hospital Parc Taulí	Recruiting
Sabadell, Barcelona, Spain, 08208
Contact: Arantxa Gelabert, MD
Contact: Francisco J Garcia Borobia, MD
Principal Investigator: Arantxa Gelabert
Principal Investigator: Francisco J Garcia Borobia
Hospital Universitari Mútua Terrassa	Completed
Terrassa, Barcelona, Spain, 08221
Hospital Universitari Dr. Josep Trueta	Recruiting
Girona, Gerona, Spain, 17007
Contact: Jaume Codina Font, MD PhD
Contact: Santi Lopez Ben
Principal Investigator: Jaume Codina font, MD PhD
Principal Investigator: Santi Lopez Ben, MD PhD
Sub-Investigator: Margarida Casellas, MD PhD
Clínic de Barcelona	Recruiting
Barcelona, Spain, 08036
Contact: Constantino Fondevilla, MD PhD
Contact: Fernando Gómez, MD PhD
Principal Investigator: Constantino Fondevilla, MD PhD
Principal Investigator: Fernando Gómez, MD PhD
Sub-Investigator: Yiliam Fundora, MD PhD
Sub-Investigator: Silvia Fernandez
University Hospital Miguel Servet	Recruiting
Zaragoza, Spain, 50009
Contact: Alejandro Serrablo, MD PhD
Contact: Luis Sarria, Md PhD
Principal Investigator: Alejandro Serrablo, MD PhD
Principal Investigator: Joaquin Medrano, MD PhD
Principal Investigator: Luis Luis Sarria, MD PhD
Sweden
Linköping University Hospital	Completed
Linköping, Sweden, 581 85
Karolinska University Hospital	Completed
Stockholm, Sweden, 14186
Switzerland
Claraspital & Clarunis University Hospital Basel	Completed
Basel, Basel-Stadt, Switzerland, CH-4058
Kantonsspital Winterthur (KSW)	Completed
Winterthur, Switzerland, 8401
United Kingdom
University Hospital Southampton	Completed
Southampton, Hampshire, United Kingdom, SO16 6YD
Aintree University Hospital	Completed
Liverpool, Merseyside, United Kingdom, L9 7AL
Belfast Health and Social Care Trust	Recruiting
Belfast, United Kingdom
Contact: David Vass
Principal Investigator: David Vass, MD PhD
Principal Investigator: Ridchard Lindsay, MD PhD
Sub-Investigator: Mark Taylor, MD PhD
Sub-Investigator: Stephen McCain, MD PhD
Sub-Investigator: Peter Kennedy, MD PhD
King's college hospital NHS foundation trust	Recruiting
London, United Kingdom
Contact: Krishna Menon
Principal Investigator: Krishna Menon, MD PhD
Principal Investigator: Praveen Peddu, MD PhD
Oxford University Hospitals NHS Foundation Trust	Recruiting
Oxford, United Kingdom
Contact: Katherine Gordon-Quayle
Principal Investigator: Venkatesha Udupa, MD PhD
Principal Investigator: Andrew Macdonald, MD PhD

Sponsors and Collaborators

Maastricht University

Koningin Wilhelmina Fonds

Investigators

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Principal Investigator:	Ronald M van Dam, MD PhD	Maastricht University Medical Center
Principal Investigator:	Erik Schadde, MD FACS FEBS	Kantonsspital Winterthur/ Rush University Medical Center, Chicago
Principal Investigator:	Marc AH Bemelmans, MD PhD	Maastricht University Medical Center
Principal Investigator:	Christiaan van der Leij, MD PhD	Maastricht University Medical Center
Principal Investigator:	Christoph A Binkert, Prof.Dr.Med	Cantonal Hospital Winterthur

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Korenblik R, Olij B, Aldrighetti LA, Hilal MA, Ahle M, Arslan B, van Baardewijk LJ, Baclija I, Bent C, Bertrand CL, Björnsson B, de Boer MT, de Boer SW, Bokkers RPH, Rinkes IHMB, Breitenstein S, Bruijnen RCG, Bruners P, Büchler MW, Camacho JC, Cappelli A, Carling U, Chan BKY, Chang DH, Choi J, Font JC, Crawford M, Croagh D, Cugat E, Davis R, De Boo DW, De Cobelli F, De Wispelaere JF, van Delden OM, Delle M, Detry O, Díaz-Nieto R, Dili A, Erdmann JI, Fisher O, Fondevila C, Fretland Å, Borobia FG, Gelabert A, Gérard L, Giuliante F, Gobardhan PD, Gómez F, Grünberger T, Grünhagen DJ, Guitart J, Hagendoorn J, Heil J, Heise D, Herrero E, Hess GF, Hoffmann MH, Iezzi R, Imani F, Nguyen J, Jovine E, Kalff JC, Kazemier G, Kingham TP, Kleeff J, Kollmar O, Leclercq WKG, Ben SL, Lucidi V, MacDonald A, Madoff DC, Manekeller S, Martel G, Mehrabi A, Mehrzad H, Meijerink MR, Menon K, Metrakos P, Meyer C, Moelker A, Modi S, Montanari N, Navines J, Neumann UP, Peddu P, Primrose JN, Qu X, Raptis D, Ratti F, Ridouani F, Rogan C, Ronellenfitsch U, Ryan S, Sallemi C, Moragues JS, Sandström P, Sarriá L, Schnitzbauer A, Serenari M, Serrablo A, Smits MLJ, Sparrelid E, Spüntrup E, Stavrou GA, Sutcliffe RP, Tancredi I, Tasse JC, Udupa V, Valenti D, Fundora Y, Vogl TJ, Wang X, White SA, Wohlgemuth WA, Yu D, Zijlstra IAJ, Binkert CA, Bemelmans MHA, van der Leij C, Schadde E, van Dam RM. Dragon 1 Protocol Manuscript: Training, Accreditation, Implementation and Safety Evaluation of Portal and Hepatic Vein Embolization (PVE/HVE) to Accelerate Future Liver Remnant (FLR) Hypertrophy. Cardiovasc Intervent Radiol. 2022 Jul 5. doi: 10.1007/s00270-022-03176-1. [Epub ahead of print]

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Responsible Party:	Maastricht University
ClinicalTrials.gov Identifier:	NCT04272931
Other Study ID Numbers:	NL71535.068.19
First Posted:	February 17, 2020 Key Record Dates
Last Update Posted:	July 12, 2022
Last Verified:	July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Maastricht University:


Future Liver Remnant Portal and Hepatic Vein Embolization Colorectal Liver Metastases

Additional relevant MeSH terms:

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Neoplasm Metastasis Neoplasms Neoplastic Processes Pathologic Processes

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