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

NCT ID: NCT04272931

Last Updated: 2023-02-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 111 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-08
• Study Completion Date: 2023-12-31

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).

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.

Conditions

Colorectal Cancer Liver Metastases

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Portal and Hepatic Vein Embolization

Intervention Type: 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)

Interventions

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)

Intervention Type: PROCEDURE

Other Intervention Names

Liver venous deprivation (LVD); Double embolization

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Koningin Wilhelmina Fonds

OTHER

Sponsor Role: collaborator

Maastricht University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ronald M van Dam, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Maastricht University Medical Center

Erik Schadde, MD FACS FEBS

Role: PRINCIPAL_INVESTIGATOR

Kantonsspital Winterthur/ Rush University Medical Center, Chicago

Marc AH Bemelmans, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Maastricht University Medical Center

Christiaan van der Leij, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Maastricht University Medical Center

Christoph A Binkert, Prof.Dr.Med

Role: PRINCIPAL_INVESTIGATOR

Cantonal Hospital Winterthur

Locations

Yale School of Medicine

New Haven, Connecticut, United States

Rush University Medical Center

Chicago, Illinois, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Monash Health, Clayton

Clayton, Victoria, Australia

Social Medical Center, South

Vienna, , Austria

Hôpital Erasme

Brussels, Brussels Capital, Belgium

CHU-UCL Namur site Godinne

Yvoir, Namen, Belgium

CHU de Liège

Liège, , Belgium

The Ottawa Hospital

Ottawa, Ontario, Canada

McGill University Health Center

Montreal, , Canada

Klinikum Saarbrücken gGmbH

Saarbrücken, Saarland, Germany

University Hospital Halle (Saale)

Halle, Saxony-Anhalt, Germany

Frankfurt University Hospital

Frankfurt, , Germany

Policlinico Sant'Orsola-Malpighi

Bologna, , Italy

Fondazione Poliambulanza

Brescia, , Italy

IRCCS San Raffaele Hospital

Milan, , Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, , Italy

Maastricht University Medical Center+

Maastricht, Limburg, Netherlands

Amsterdam UMC, location AMC

Amsterdam, North Holland, Netherlands

Erasmus Medical Center

Rotterdam, South Holland, Netherlands

Amsterdam Medical Centers, Location VUmc

Amsterdam, , Netherlands

Amphia

Breda, , Netherlands

Maxima Medisch Centrum

Eindhoven, , Netherlands

University Medical Center Groningen

Groningen, , Netherlands

Universitair Medisch Centrum Utrecht

Utrecht, , Netherlands

Oslo University Hospital

Oslo, , Norway

University Hospital Germans Trias I Pujol

Badalona, Barcelona, Spain

University Hospital Parc Taulí

Sabadell, Barcelona, Spain

Hospital Universitari Mútua Terrassa

Terrassa, Barcelona, Spain

Hospital Universitari Dr. Josep Trueta

Girona, Gerona, Spain

Clínic de Barcelona

Barcelona, , Spain

University Hospital Miguel Servet

Zaragoza, , Spain

Linköping University Hospital

Linköping, , Sweden

Karolinska University Hospital

Stockholm, , Sweden

Claraspital & Clarunis University Hospital Basel

Basel, Canton of Basel-City, Switzerland

Kantonsspital Winterthur (KSW)

Winterthur, , Switzerland

University Hospital Southampton

Southampton, Hampshire, United Kingdom

Aintree University Hospital

Liverpool, Merseyside, United Kingdom

Belfast Health and Social Care Trust

Belfast, , United Kingdom

King's college hospital NHS foundation trust

London, , United Kingdom

Oxford University Hospitals NHS Foundation Trust

Oxford, , United Kingdom

Countries

United States; Australia; Austria; Belgium; Canada; Germany; Italy; Netherlands; Norway; Spain; Sweden; Switzerland; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 40255933 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35790566 (View on PubMed)

Other Identifiers

NL71535.068.19

Identifier Type: -

Identifier Source: org_study_id