DRAGON 1- Training, Accreditation, Implementation and Safety Evaluation of Combined PVE/HVE
- Conditions
- Colorectal Cancer Liver Metastases
- Interventions
- Procedure: Portal and Hepatic Vein Embolization
- Registration Number
- NCT04272931
- Lead Sponsor
- Maastricht University
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 111
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Portal and Hepatic Vein Embolization 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.
- Primary Outcome Measures
Name Time Method Ability of each center to enroll 3 patients in 12 months without mortality due to the intervention. 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
Name Time Method Liver specific complication assessment 90 days 90-day complications, liver specific (FABIB-classification)
Overall survival after PVE/HVE 1 year follow up Overall survival
Oncological effectiveness of PVE/HVE 1 year Disease-free survival after 1 year
Mortality assessment 90 days 90-mortality after resection
General complication assessment 90 days 90-day complications, general (Clavien-Dindo)
Efficacy assessment: standardized future liver remnant volume 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 1 year follow up ion of patients proceeding to complete resection (=resection rate)
Trial Locations
- Locations (42)
CHU-UCL Namur site Godinne
🇧🇪Yvoir, Namen, Belgium
Amsterdam UMC, location AMC
🇳🇱Amsterdam, Noord-Holland, Netherlands
Monash Health, Clayton
🇦🇺Clayton, Victoria, Australia
Amsterdam Medical Centers, Location VUmc
🇳🇱Amsterdam, Netherlands
Yale School of Medicine
🇺🇸New Haven, Connecticut, United States
CHU de Liège
🇧🇪Liège, Belgium
McGill University Health Center
🇨🇦Montréal, Canada
Claraspital & Clarunis University Hospital Basel
🇨ðŸ‡Basel, Basel-Stadt, Switzerland
Klinikum Saarbrücken gGmbH
🇩🇪Saarbrücken, Saarland, Germany
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
Social Medical Center, South
🇦🇹Vienna, Austria
Hôpital Erasme
🇧🇪Brussels, Bruxelles, Belgium
The Ottawa Hospital
🇨🇦Ottawa, Ontario, Canada
University Hospital Halle (Saale)
🇩🇪Halle (Saale), Saksen-Anhalt, Germany
Policlinico Sant'Orsola-Malpighi
🇮🇹Bologna, Italy
Frankfurt University Hospital
🇩🇪Frankfurt, Germany
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
Erasmus Medical Center
🇳🇱Rotterdam, Zuid-Holland, Netherlands
Maxima Medisch Centrum
🇳🇱Eindhoven, Netherlands
Amphia
🇳🇱Breda, 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 TaulÃ
🇪🇸Sabadell, Barcelona, Spain
Hospital Universitari Mútua Terrassa
🇪🇸Terrassa, Barcelona, Spain
University Hospital Miguel Servet
🇪🇸Zaragoza, Spain
Hospital Universitari Dr. Josep Trueta
🇪🇸Girona, Gerona, Spain
ClÃnic de Barcelona
🇪🇸Barcelona, Spain
Linköping University Hospital
🇸🇪Linköping, Sweden
Karolinska University Hospital
🇸🇪Stockholm, Sweden
University Hospital Southampton
🇬🇧Southampton, Hampshire, United Kingdom
Aintree University Hospital
🇬🇧Liverpool, Merseyside, United Kingdom
Kantonsspital Winterthur (KSW)
🇨ðŸ‡Winterthur, Switzerland
King's college hospital NHS foundation trust
🇬🇧London, United Kingdom
Oxford University Hospitals NHS Foundation Trust
🇬🇧Oxford, United Kingdom
Belfast Health and Social Care Trust
🇬🇧Belfast, United Kingdom