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

NCT04272931 | Unknown DMC

• 1 other identifier: NL71535.068.19
• Study Type: interventional
• Target: 111
• Locations: 12 countries
• Sites: 41

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).

Conditions

Colorectal Cancer Liver Metastases

Keywords

Future Liver Remnant; Portal and Hepatic Vein Embolization; Colorectal Liver Metastases

Outcome Measures

Primary Outcomes (1)

• Ability of each center to enroll 3 patients in 12 months without mortality due to the intervention.

  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.

  1 year/ 90 day mortality

Secondary Outcomes (7)

• Efficacy assessment: standardized future liver remnant volume

  6 weeks

• Feasibility assessment: resection rate

  1 year follow up

• Mortality assessment

  90 days

• Overall survival after PVE/HVE

  1 year follow up

• Oncological effectiveness of PVE/HVE

  1 year

Study Arms (1)

Portal and Hepatic Vein Embolization

EXPERIMENTAL

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

Interventions

Portal and Hepatic Vein Embolization PROCEDURE

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)

Also known as: Liver venous deprivation (LVD), Double embolization

Portal and Hepatic Vein Embolization

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with primarily unresectable/potentially resectable CRLM after conversion chemotherapy with a FLR \<30% in normal livers, or 40% in livers chemotherapy damaged livers.
• 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.

You may not qualify if:

• 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.)

Sponsors & Collaborators

• Maastricht University: lead
• Koningin Wilhelmina Fonds: collaborator

Study Sites (42)

Yale School of Medicine

New Haven, Connecticut, 06510, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, NSW 2050, Australia

Location

Monash Health, Clayton

Clayton, Victoria, VIC 3168, Australia

Location

Social Medical Center, South

Vienna, 1100, Austria

Location

Hôpital Erasme

Brussels, Brussels Capital, 1070, Belgium

Location

CHU-UCL Namur site Godinne

Yvoir, Namen, 5530, Belgium

Location

CHU de Liège

Liège, 4000, Belgium

Location

The Ottawa Hospital

Ottawa, Ontario, k1H 8L6, Canada

Location

McGill University Health Center

Montreal, Canada

Location

Klinikum Saarbrücken gGmbH

Saarbrücken, Saarland, 66119, Germany

Location

University Hospital Halle (Saale)

Halle, Saxony-Anhalt, 06120, Germany

Location

Frankfurt University Hospital

Frankfurt, Germany

Location

Policlinico Sant'Orsola-Malpighi

Bologna, 40138, Italy

Location

Fondazione Poliambulanza

Brescia, 25124, Italy

Location

IRCCS San Raffaele Hospital

Milan, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 00168 Roma, Italy

Location

Maastricht University Medical Center+

Maastricht, Limburg, 6229 HX, Netherlands

Location

Amsterdam UMC, location AMC

Amsterdam, North Holland, 1105 AZ, Netherlands

Location

Erasmus Medical Center

Rotterdam, South Holland, 3015, Netherlands

Location

Amsterdam Medical Centers, Location VUmc

Amsterdam, 1081HV, Netherlands

Location

Amphia

Breda, Netherlands

Location

Maxima Medisch Centrum

Eindhoven, Netherlands

Location

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

Universitair Medisch Centrum Utrecht

Utrecht, Netherlands

Location

Oslo University Hospital

Oslo, 0450 Oslo, Norway

Location

University Hospital Germans Trias I Pujol

Badalona, Barcelona, 08916 Badalona, Spain

Location

University Hospital Parc Taulí

Sabadell, Barcelona, 08208, Spain

Location

Hospital Universitari Mútua Terrassa

Terrassa, Barcelona, 08221, Spain

Location

Hospital Universitari Dr. Josep Trueta

Girona, Gerona, 17007, Spain

Location

Clínic de Barcelona

Barcelona, 08036, Spain

Location

University Hospital Miguel Servet

Zaragoza, 50009, Spain

Location

Linköping University Hospital

Linköping, 581 85, Sweden

Location

Karolinska University Hospital

Stockholm, 14186, Sweden

Location

Claraspital & Clarunis University Hospital Basel

Basel, Canton of Basel-City, CH-4058, Switzerland

Location

Kantonsspital Winterthur (KSW)

Winterthur, 8401, Switzerland

Location

University Hospital Southampton

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

Aintree University Hospital

Liverpool, Merseyside, L9 7AL, United Kingdom

Location

Belfast Health and Social Care Trust

Belfast, United Kingdom

Location

King's college hospital NHS foundation trust

London, United Kingdom

Location

Oxford University Hospitals NHS Foundation Trust

Oxford, United Kingdom

Location

Related Publications (2)

• Korenblik R, James S, Smits J, Diaz-Nieto R, Davis R, Chan BKY, Erdmann JI, Zijlstra IAJ, Arntz PJW, Kollmar O, Hoffmann MH, Vass DG, Lindsay R, Serenari M, Cappelli A, Gobardhan PD, Imani F, Suarez YF, Munos FG, Grunhagen DJ, Moelker A, Pieterman KJ, Kleeff J, Wohlgemuth WA, Herrero E, Gelabert A, Breitenstein S, Seeger N, Detry O, Gerard L, Sandstrom PA, Bjornsson B, Aldrighetti LA, De Cobelli F, Leclercq WKG, van Baardewijk LJ, Croagh D, De Boo DW, Kingham TP, Ridouani F, Metrakos P, Valenti D, Kalil J, Fretland AA, Carling U, Martel G, Ryan S, Udupa V, Macdonald A, Tasse JC, Stavrou GA, Spuentrup E, Borobia FG, Criado E, Sparrelid E, Delle M, Navines-Lopez J, Moragues JS, Andorra EC, Schnitzbauer A, Vogl TJ, Heil J, Primrose JN, Modi S, Fouraschen SMG, Bokkers RPH, de Boer MT, Borel Rinkes IHM, Smits MLJ, Gruenberger T, Baclija I, Billingsley KG, Madoff DC, Serrablo A, Sarria L, Wang X, Xudong Q, Winkens B, Olde Damink SWL, Bemelmans MHA, Dewulf MJL, Binkert CA, Schadde E, van der Leij C, van Dam RM; DRAGON collaborative study group. Safety and efficacy of combined portal and hepatic vein embolisation in patients with colorectal liver metastases (DRAGON1): a multicentre, single-arm clinical trial. Lancet Reg Health Eur. 2025 Apr 10;53:101284. doi: 10.1016/j.lanepe.2025.101284. eCollection 2025 Jun.

  PMID: 40255933 DERIVED

• Korenblik R, Olij B, Aldrighetti LA, Hilal MA, Ahle M, Arslan B, van Baardewijk LJ, Baclija I, Bent C, Bertrand CL, Bjornsson B, de Boer MT, de Boer SW, Bokkers RPH, Rinkes IHMB, Breitenstein S, Bruijnen RCG, Bruners P, Buchler 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, Diaz-Nieto R, Dili A, Erdmann JI, Fisher O, Fondevila C, Fretland A, Borobia FG, Gelabert A, Gerard L, Giuliante F, Gobardhan PD, Gomez F, Grunberger T, Grunhagen 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, Sandstrom P, Sarria L, Schnitzbauer A, Serenari M, Serrablo A, Smits MLJ, Sparrelid E, Spuntrup 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 Sep;45(9):1391-1398. doi: 10.1007/s00270-022-03176-1. Epub 2022 Jul 5.

  PMID: 35790566 DERIVED

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: January 7, 2020
• First Posted: February 17, 2020
• Study Start: May 8, 2020
• Primary Completion: October 1, 2022
• Study Completion: December 31, 2023
• Last Updated: February 3, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Study protocol has already been published : https://pubmed.ncbi.nlm.nih.gov/35790566/ Other information may be shared upon reasonable request after publication

Locations

US (3); AU (2); NO (1); SE (2); BE (3); IT (4); GB (5); CA (2); DE (3); NL (8); ES (6); CH (2)