Clinical trial NCT05428735: The DRAGON 2 Trial
Official title: An International Multicenter Randomized Controlled Trial to Compare Combined Portal and Hepatic Vein Embolization (PVE/HVE) with PVE Alone in Patients with Colorectal Liver Cancer Metastases (CRLM) and a Small Future Liver Remnant (FLR)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Colorectal Cancer Liver Metastases (CRLM)
Small Future Liver Remnant (FLR)
Lead sponsor: Maastricht University
Sponsor class: OTHER
First posted: 2022-06-23
Enrollment: 348
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: In the randomized controlled DRAGON 2 trial study subjects will be randomized between two arms, PVE alone (control group) and PVE/HVE (interventional group).

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. Extended liver resections are sometimes necessary to resect primarily unresectable/ potentially resectable (PU/PR) colorectal liver metastases. These resections are generally performed if the volume of the future liver remnant (FLR) comprises at least 30% of the total volume of the liver (without the volume of the metastases) or when liver function of the FLR on technetium-99m (99mTc) scintigraphy exceeds 2.67%/min/m2.

When this liver volume or function criterion is not met, a high chance of post-hepatectomy liver failure exists. To prevent this, the induction of liver regeneration between a two-stage hepatectomy is commonly performed.

The current standard procedure to induce regeneration is the embolization of the portal vein branches to the tumor carrying liver (PVE) to induce hypertrophy of the remaining part of the liver which will serve as the FLR. Recently, combined embolization of both portal and hepatic veins (PVE/HVE) has been described as a possible superior alternative to PVE, as it increases and accelerates hypertrophy of the FLR. PVE/HVE combines simultaneous embolization of the main portal vein branches into the tumor carrying liver and the hepatic vein draining this part of the liver. Preclinical studies in pigs, several retrospective studies, and the prospective DRAGON 1 interim analysis (n=60) have demonstrated the safety and feasibility of this novel technique. However, no international randomized controlled trial has been performed, in which combined PVE/HVE is compared with PVE

Eligibility criteria: Inclusion Criteria:

* Patients with primarily unresectable/ potentially resectable CRLM with a FLR \<30% (\<40% in chemotherapy damaged livers)
* Patients with non-resected primary CRC may be included if there is an intention to resect the CRC after the liver treatment (liver first approach) or simultaneously during one of the liver procedures.
* Patients with resectable or ablatable lung or brain metastases can be included (statement about the resectability of these extrahepatic metastases by a tumor board needs to be available)
* 18 Years and older
* Men and women
* Able to understand the trial and provide informed consent.

Exclusion Criteria:

* Pregnant or lactating female.
* Premenopausal females not able or willing to commit to oral contraception
* Patients with prohibitive comorbidities, decision made by local team
* Any patient with non-resectable or non-ablatable extrahepatic disease
* Patients with hepatic malignancies other than CRLM
* Progression of disease by RECIST criteria after cytoreduction chemotherapy
* Complete response after conversion chemotherapy
* Staging CT and (if indicated) CT/MRI brain that demonstrates non-resectable extrahepatic disease
* The anatomy of the liver or manifestation of tumors in relation to the liver veins prohibits the use of combined PVE/HVE.

Primary outcomes:
measure: Volume sufficient for resection at week 3 after the embolization
timeFrame: 3 weeks
measure: 5-year Overall Survival
timeFrame: 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Clayton
country: Australia
facility: Monash Medical Centre
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: Gent
country: Belgium
facility: UZ Gent
state: Oost-Vlaanderen
city: Liège
country: Belgium
facility: CHU de Liège
city: Vancouver
country: Canada
facility: Vancouver Coastal Health
state: British Columbia
city: Hamilton
country: Canada
facility: Juravinski Hospital and Cancer Centre
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Hospital
state: Ontario
city: Montréal
country: Canada
facility: McGill University Health Center
city: Milan
country: Italy
facility: IRCCS San Raffaele Hospital
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: 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: 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)
Study officials:
affiliation: Maastricht Universitair Medisch Centrum
name: Ronald M. van Dam, PhD
role: PRINCIPAL_INVESTIGATOR
References: