Clinical trial NCT04272931: DRAGON 1- Training, Accreditation, Implementation and Safety Evaluation of Combined PVE/HVE
Official title: DRAGON 1- Training, Accreditation, Implementation and Safety Evaluation of Portal and Hepatic Vein Embolization to Accelerate Future Liver Remnant (FLR) Hypertrophy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Colorectal Cancer Liver Metastases
Keywords: Future Liver Remnant
Portal and Hepatic Vein Embolization
Colorectal Liver Metastases
Lead sponsor: Maastricht University
Sponsor class: OTHER
Collaborators: name: Koningin Wilhelmina Fonds
First posted: 2020-02-17
Enrollment: 111
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Ability of each center to enroll 3 patients in 12 months without mortality due to the intervention.
timeFrame: 1 year/ 90 day mortality
Secondary outcomes:
measure: Efficacy assessment: standardized future liver remnant volume
timeFrame: 6 weeks
measure: Feasibility assessment: resection rate
timeFrame: 1 year follow up
measure: Mortality assessment
timeFrame: 90 days
measure: Overall survival after PVE/HVE
timeFrame: 1 year follow up
measure: Oncological effectiveness of PVE/HVE
timeFrame: 1 year
measure: General complication assessment
timeFrame: 90 days
measure: Liver specific complication assessment
timeFrame: 90 days
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale School of Medicine
state: Connecticut
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Clayton
country: Australia
facility: Monash Health, Clayton
state: Victoria
city: Vienna
country: Austria
facility: Social Medical Center, South
city: Brussels
country: Belgium
facility: Hôpital Erasme
state: Bruxelles
city: Yvoir
country: Belgium
facility: CHU-UCL Namur site Godinne
state: Namen
city: Liège
country: Belgium
facility: CHU de Liège
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Montréal
country: Canada
facility: McGill University Health Center
city: Saarbrücken
country: Germany
facility: Klinikum Saarbrücken gGmbH
state: Saarland
city: Halle (Saale)
country: Germany
facility: University Hospital Halle (Saale)
state: Saksen-Anhalt
city: Frankfurt
country: Germany
facility: Frankfurt University Hospital
city: Bologna
country: Italy
facility: Policlinico Sant'Orsola-Malpighi
city: Brescia
country: Italy
facility: Fondazione Poliambulanza
city: Milan
country: Italy
facility: IRCCS San Raffaele Hospital
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center+
state: Limburg
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, location AMC
state: Noord-Holland
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
state: Zuid-Holland
city: Amsterdam
country: Netherlands
facility: Amsterdam Medical Centers, Location VUmc
city: Breda
country: Netherlands
facility: Amphia
city: Eindhoven
country: Netherlands
facility: Maxima Medisch Centrum
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Badalona
country: Spain
facility: University Hospital Germans Trias I Pujol
state: Barcelona
city: Sabadell
country: Spain
facility: University Hospital Parc Taulí
state: Barcelona
city: Terrassa
country: Spain
facility: Hospital Universitari Mútua Terrassa
state: Barcelona
city: Girona
country: Spain
facility: Hospital Universitari Dr. Josep Trueta
state: Gerona
city: Barcelona
country: Spain
facility: Clínic de Barcelona
city: Zaragoza
country: Spain
facility: University Hospital Miguel Servet
city: Linköping
country: Sweden
facility: Linköping University Hospital
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Basel
country: Switzerland
facility: Claraspital & Clarunis University Hospital Basel
state: Basel-Stadt
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur (KSW)
city: Southampton
country: United Kingdom
facility: University Hospital Southampton
state: Hampshire
city: Liverpool
country: United Kingdom
facility: Aintree University Hospital
state: Merseyside
city: Belfast
country: United Kingdom
facility: Belfast Health and Social Care Trust
city: London
country: United Kingdom
facility: King's college hospital NHS foundation trust
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
Study officials:
affiliation: Maastricht University Medical Center
name: Ronald M van Dam, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kantonsspital Winterthur/ Rush University Medical Center, Chicago
name: Erik Schadde, MD FACS FEBS
role: PRINCIPAL_INVESTIGATOR
affiliation: Maastricht University Medical Center
name: Marc AH Bemelmans, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Maastricht University Medical Center
name: Christiaan van der Leij, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cantonal Hospital Winterthur
name: Christoph A Binkert, Prof.Dr.Med
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.