DRAGON 1- Training, Accreditation, Implementation and Safety Evaluation of Combined PVE/HVE

Colorectal Cancer Liver Metastases Clinical Trial

— DRAGON  

Official title:

DRAGON 1- Training, Accreditation, Implementation and Safety Evaluation of Portal and Hepatic Vein Embolization to Accelerate Future Liver Remnant (FLR) Hypertrophy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04272931
• Other study ID #: NL71535.068.19
• Status: Active, not recruiting
• Phase: N/A
• Start date: May 8, 2020
• Est. completion date: December 31, 2023

Study information

• Verified date: February 2023
• Source: Maastricht University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 111
• Est. completion date: December 31, 2023
• Est. primary completion date: October 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Cancer Liver Metastases
• Neoplasm Metastasis

Intervention

Procedure:
• Portal and Hepatic Vein Embolization
Procedure/Surgery: Combined portal vein embolization and hepatic vein embolization (PVE/HVE) • All techniques of PVE allowed (ipsi-lateral, contra-lateral, trans-splenic, all embolization agents except for ethanol alone) • All modifications of HVE allowed (venous occlusion umbrellas; trans-jugular, trans-hepatic, no use of vein glue to avoid lung embolization; staged approach allowed, but first PVE, then HVE and within 48 hours)

Locations

Country	Name	City	State
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Monash Health, Clayton	Clayton	Victoria
Austria	Social Medical Center, South	Vienna
Belgium	Hôpital Erasme	Brussels	Bruxelles
Belgium	CHU de Liège	Liège
Belgium	CHU-UCL Namur site Godinne	Yvoir	Namen
Canada	McGill University Health Center	Montréal
Canada	The Ottawa Hospital	Ottawa	Ontario
Germany	Frankfurt University Hospital	Frankfurt
Germany	University Hospital Halle (Saale)	Halle (Saale)	Saksen-Anhalt
Germany	Klinikum Saarbrücken gGmbH	Saarbrücken	Saarland
Italy	Policlinico Sant'Orsola-Malpighi	Bologna
Italy	Fondazione Poliambulanza	Brescia
Italy	IRCCS San Raffaele Hospital	Milan
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma
Netherlands	Amsterdam Medical Centers, Location VUmc	Amsterdam
Netherlands	Amsterdam UMC, location AMC	Amsterdam	Noord-Holland
Netherlands	Amphia	Breda
Netherlands	Maxima Medisch Centrum	Eindhoven
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Maastricht University Medical Center+	Maastricht	Limburg
Netherlands	Erasmus Medical Center	Rotterdam	Zuid-Holland
Netherlands	Universitair Medisch Centrum Utrecht	Utrecht
Norway	Oslo University Hospital	Oslo
Spain	University Hospital Germans Trias I Pujol	Badalona	Barcelona
Spain	Clínic de Barcelona	Barcelona
Spain	Hospital Universitari Dr. Josep Trueta	Girona	Gerona
Spain	University Hospital Parc Taulí	Sabadell	Barcelona
Spain	Hospital Universitari Mútua Terrassa	Terrassa	Barcelona
Spain	University Hospital Miguel Servet	Zaragoza
Sweden	Linköping University Hospital	Linköping
Sweden	Karolinska University Hospital	Stockholm
Switzerland	Claraspital & Clarunis University Hospital Basel	Basel	Basel-Stadt
Switzerland	Kantonsspital Winterthur (KSW)	Winterthur
United Kingdom	Belfast Health and Social Care Trust	Belfast
United Kingdom	Aintree University Hospital	Liverpool	Merseyside
United Kingdom	King's college hospital NHS foundation trust	London
United Kingdom	Oxford University Hospitals NHS Foundation Trust	Oxford
United Kingdom	University Hospital Southampton	Southampton	Hampshire
United States	Rush University Medical Center	Chicago	Illinois
United States	Yale School of Medicine	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Maastricht University	Koningin Wilhelmina Fonds

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Germany,  Italy,  Netherlands,  Norway,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ability of each center to enroll 3 patients in 12 months without mortality due to the intervention.	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.	1 year/ 90 day mortality
Secondary	Efficacy assessment: standardized future liver remnant volume	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	6 weeks
Secondary	Feasibility assessment: resection rate	ion of patients proceeding to complete resection (=resection rate)	1 year follow up
Secondary	Mortality assessment	90-mortality after resection	90 days
Secondary	Overall survival after PVE/HVE	Overall survival	1 year follow up
Secondary	Oncological effectiveness of PVE/HVE	Disease-free survival after 1 year	1 year
Secondary	General complication assessment	90-day complications, general (Clavien-Dindo)	90 days
Secondary	Liver specific complication assessment	90-day complications, liver specific (FABIB-classification)	90 days