Clinical trial NCT06914648: The Dragon PLC Trial (DRAGON-PLC)
Official title: The DRAGON PLC Trial - An International Multicenter Randomized Controlled Trial to Compare Combined Portal and Hepatic Vein Embolization (PVE/HVE) With PVE Alone in Primary Liver Cancers.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Primary Liver Cancer
Hepatocellular Carcinoma (HCC)
Cholangiocarcinoma
Keywords: Primary liver cancer
Future Liver Remnant
Liver regeneration
Portal Vein Embolization (PVE)
Hepatic Vein Embolization (HVE)
Lead sponsor: Maastricht University
Sponsor class: OTHER
First posted: 2025-04-06
Enrollment: 358
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1:1 Randomization between control and interventional group
Primary purpose: TREATMENT

Brief summary: The goal of the DRAGON PLC clinical trial is to determine whether portal vein embolization (PVE) combined with hepatic vein embolization (HVE) improves resectability and overall survival in patients with initially unresectable primary liver cancer compared to standard PVE alone. This trial specifically focuses on patients with hepatocellular carcinoma and cholangiocarcinoma.

The main questions this trial aims to answer are whether combined PVE and HVE increases the proportion of patients who become resectable within 3 weeks and improves 5-year overall survival compared to PVE alone by enhancing liver hypertrophy.

Participants will:

* Undergo either standard PVE or combined PVE and HVE.
* Have regular imaging to assess liver resectability.
* Be monitored for survival outcomes up to 5 years after intervention.

Detailed description: Primary liver cancer (PLC) is the third most common cause of cancer death worldwide. Surgical resection is the mainstay for a curative approach as contemporary chemotherapy and immune-based therapies only lead to a median survival of 10-14 months. A complete surgical resection increases the median survival to 42 months (range 32-52 months). However, PLC is mainly diagnosed at an advanced stage and \>70% of PLC patients are ineligible for an immediate surgical approach. There are different reasons that make a patient ineligible for surgery, one important reason is the risk of liver failure after the surgery due to a small remnant liver.

This study aims to improve the oncological, radiological and surgical strategy to allow more patients to undergo liver resection safely, to improve quality of life and to extend overall survival at acceptable costs.

Adequate function of the future liver remnant (FLR) is a prerequisite for surgical resectability. This is necessary in order to avoid liver failure after surgery, a major cause of morbidity (38%) and mortality (27%). To mitigate this risk, regenerative strategies based on preoperative calculation of the FLR volume and function are essential. Patients with technically resectable disease but predicted insufficient FLR volume or function are referred to as primarily unresectable or potentially resectable (PU/PR). These patients can undergo strategies that capitalize on the regenerative capacity of the liver which aim to preoperatively increase the FLR volume and function in order to allow surgery. Many of the patients that are primarily unresectable due to an insufficient FLR can become ultimately and safely resectable after the induction of adequate FLR-hypertrophy by the current standard, portal vein embolisation (PVE). However, 25% of patients do not show sufficient FLR growth after PVE and are unable to safely undergo resection. A new approach has been developed to improve this. Combined portal and hepatic vein embolisation (PVE/HVE) has great promise in terms of increasing FLR growth, resection rate (RR), safety and potentially, overall survival. Establishing PVE/HVE as the new standard could result in increased survival and a better quality of life (QoL) for patients.

Eligibility criteria: Inclusion Criteria:

* PLC diagnosis, specifically iCCC, pCCC, and HCC;
* Requiring PVE due to an FLR volume is \<30% in normally functioning livers, \<40% in livers with potentially impaired function e.g. resulting from prior systemic therapy induction or bile duct colonization / transpapillary biliary drainage, or \<50% in livers with severely impaired function resulting from liver cirrhosis (max. Child Pugh A5) OR function on hepatobiliary scintigraphy (HEBIS) is \< 2.7 %/min/m2;
* Age ≥ 18 years;
* Able to understand the trial and provide informed consent.

Exclusion Criteria:

* Liver cirrhosis with a Child-Pugh score of B or C;
* Presence of portal hypertension;
* Presence of cholangitis;
* Pregnant women;
* Premenopausal females not able/willing to commit to contraception (specifically long-acting reversible contraception or hormonal contraception);
* Patients unresectable due to prohibitive comorbidities (decision made by local multidisciplinary team);
* Patients with hepatic malignancies other than iCCC, pCCC or HCC;
* PVE/HVE anatomically not feasible;
* Any patient with non-resectable or non-ablatable extrahepatic metastatic disease.
* Unable to understand the study information, study instructions and give informed consent

Primary outcomes:
measure: Resectability 3 weeks after embolisation
timeFrame: 3 weeks
measure: Overall survival
timeFrame: 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale School of Medicine Hospital
state: Connecticut
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Melbourne
country: Australia
facility: Monash Medical Center
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Vienna
country: Austria
facility: Social Center South
city: Brussels
country: Belgium
facility: Erasmus Hospital
state: Bruxelles
city: Antwerp
country: Belgium
facility: UZ Antwerpen
state: Edegem
city: Yvoir
country: Belgium
facility: CHU-UCL Namur site Godinne (UCLouvain)
state: Namen
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint Luc, UCLouvain
city: Gent
country: Belgium
facility: UZ Gent
city: Hasselt
country: Belgium
facility: Jessa Hospital
city: Jette
country: Belgium
facility: UZ Brussel
city: Kortrijk
country: Belgium
facility: AZ Groeninge Hospital Kortrijk
city: Liège
country: Belgium
facility: CHU Liège
city: Calgary
country: Canada
facility: Foothills Medical Center
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Center
state: Nova Scotia
city: Hamilton
country: Canada
facility: Juravinski Hospital and Cancer Centre
state: Ontario
city: Kingston
country: Canada
facility: Kingston Health Sciences Centre
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: St. Joseph's Health Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Hospital
state: Ontario
city: Toronto
country: Canada
facility: University Health Network/TGH
state: Ontario
city: Sherbrooke
country: Canada
facility: Centre Hospitalier Universitaire de Sherbrooke
state: Quebec
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal
city: Montreal
country: Canada
facility: McGill University Health Centre, Montreal
city: Ottawa
country: Canada
facility: L'Hopital d'Ottawa
city: Saskatoon
country: Canada
facility: Royal University Hospital
city: Dresden
country: Germany
facility: Universitätklinikum Dresden
city: Hannover
country: Germany
facility: Universitätklinikum Hannover
city: Köln
country: Germany
facility: Universitätklinikum Köln
city: Milan
country: Italy
facility: Ospedale San Raffaele
city: Maastricht
country: Netherlands
facility: Maastricht Universitair Medisch Centrum+
state: Limburg
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, location VUMC
state: Noord Holland
city: Eindhoven
country: Netherlands
facility: Maxima Medisch Centrum
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Leiden
country: Netherlands
facility: Leiden Universitair Medisch Centrum
city: Oslo
country: Norway
facility: University Hospital Oslo
city: Linköping
country: Sweden
facility: University Hospital Linköping
city: Stockholm
country: Sweden
facility: Karolinska University Hospital Stockholm
city: Winterthur
country: Switzerland
facility: Cantonal Hospital Winterthur
state: Zürich
city: Basel
country: Switzerland
facility: Claraspital Basel
city: Basel
country: Switzerland
facility: Universitätsspital Basel
city: Lausanne
country: Switzerland
facility: CHUV - Lausanne University Hospital
city: Luzern
country: Switzerland
facility: Hirslanden Klinik St. Anna
city: Zürich
country: Switzerland
facility: Hirslanden Klinik
city: Belfast
country: United Kingdom
facility: Belfast Health and Social Care Trust
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Liverpool
country: United Kingdom
facility: Aintree University Hospital
city: London
country: United Kingdom
facility: Kings college Hospital
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
city: Southampton
country: United Kingdom
facility: University Hospital Southampton
Study officials:
References: