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)

Overview

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

Interventions

• Procedure Embolization
  Portal Vein embolization with Glue by a transhepatic approach vs. PVE and Hepatic Vein Occlusion with Vascular plugs via a transjugular or transfemoral approach in the same session as the PVE procedure

Primary outcome measures

• Volume sufficient for resection at week 3 after the embolization [Time frame: 3 weeks]
• 5-year Overall Survival [Time frame: 5 years]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Netherlands · 7 centers

• Maastricht University Medical Center+ — Maastricht
• Amsterdam UMC, location AMC — Amsterdam
• University Medical Center Groningen — Groningen
• Erasmus Medical Center — Rotterdam
• Amphia — Breda
• Maxima Medisch Centrum — Eindhoven
• Universitair Medisch Centrum Utrecht — Utrecht

Canada · 5 centers

• Vancouver Coastal Health — Vancouver
• Juravinski Hospital and Cancer Centre — Hamilton
• The Ottawa Hospital — Ottawa
• Sunnybrook Hospital — Toronto
• McGill University Health Center — Montreal

Belgium · 4 centers

• Hôpital Erasme — Brussels
• CHU de Liège — Liège
• CHU-UCL Namur site Godinne — Yvoir
• UZ Gent — Ghent

Sweden · 2 centers

• Linköping University Hospital — Linköping
• Karolinska University Hospital — Stockholm

Switzerland · 2 centers

• Claraspital & Clarunis University Hospital Basel — Basel
• Kantonsspital Winterthur (KSW) — Winterthur

United States · 1 center

• Yale New Haven Hospital — New Haven

Australia · 1 center

• Monash Medical Centre — Clayton

Austria · 1 center

• Social Medical Center, South — Vienna

Italy · 1 center

• IRCCS San Raffaele Hospital — Milan

Identifiers

NCT: NCT05428735 · NL80303.068.22

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗