Colorectal Cancer Liver Metastases (CRLM)DRAGON 2NCT05428735
The DRAGON 2 Trial
A study testing Embolization in people with Colorectal Cancer Liver Metastases (CRLM) and Small Future Liver Remnant (FLR), run by Maastricht University at 24 sites in 9 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer Liver Metastases (CRLM), Small Future Liver Remnant (FLR)
- What is being tested?
- Embolization
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 348 participants
- Where
- 24 sitesin 9 countries
- Study dates
- 1 Apr 2022to 30 Jun 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 9Show fewer
- 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.
Trial locations and contacts
24 sites in 9 countries. Contact the study team or a site near you to ask about taking part.
24 sites in 9 countries
Netherlands7 sites, 7 recruiting
- Recruiting
Amsterdam UMC, location AMC
Amsterdam, North Holland, 1105 AZ
Joris I Erdmann, MD PhD
Otto M van Delden, MD PhD
- Not yet recruiting
Amphia
Breda
Farshad Imani, MD PhD
Paul Gobardhan, MD PhD
- Recruiting
Maxima Medisch Centrum
Eindhoven
Wouter Leclercq, MD PhD
Wouter KG Leqlercq, MD PhD
- Recruiting
University Medical Center Groningen
Groningen, Provincie Groningen, 9713 GZ
Marieke T de Boer, MD PhD
Jan T Bottema
- Recruiting
Maastricht University Medical Center+
Maastricht, Limburg, 6229 HX
Remon Korenblik, MD, +31637297507, remon.korenblik@mumc.nl
Ronald M van Dam, MD, PhD, r.van.dam@mumc.nl
- Not yet recruiting
Erasmus Medical Center
Rotterdam, South Holland, 3015
Dirk J. Grünhagen, MD PhD
Adriaan Moelker, MD PhD
- Recruiting
Universitair Medisch Centrum Utrecht
Utrecht
Maarten LJ Smits, MD PhD
Jeroen Hagendoorn, MD PhD
Canada5 sites, 5 recruiting
- Recruiting
Juravinski Hospital and Cancer Centre
Hamilton, Ontario, ON L8V 5C2
Leyo Ruo
- Not yet recruiting
McGill University Health Center
Montreal
Jeniffer Kalil
Peter Metrakos, Prof
- Recruiting
The Ottawa Hospital
Ottawa, Ontario, k1H 8L6
Guillaume Martel, MD
Stephen Ryan, MD, PhD
- Recruiting
Sunnybrook Hospital
Toronto, Ontario, M4N 3M5
Paul Karanicolas
- Recruiting
Vancouver Coastal Health
Vancouver, British Columbia, V5Z 4H5
Maja Segedi
Maya Segedi
Belgium4 sites, 4 recruiting
- Recruiting
Hôpital Erasme
Brussels, Brussels Capital, 1070
Valerio Lucidi, MD PhD
Viviane van Laethem
- Recruiting
UZ Gent
Ghent, Oost-Vlaanderen, Gent (9000)
Luis Luis Abreu de Carvalho
Luis Abreu de Carvalho
- Recruiting
CHU de Liège
Liège, Liège, 4000
Celine Lambrecht
Olivier Detry
- Recruiting
CHU-UCL Namur site Godinne
Yvoir, Namen, 5530
Aelxandra Dili, MD PhD
Claude Bertrand, MD PhD
Sweden2 sites, 2 recruiting
- Recruiting
Linköping University Hospital
Linköping, 581 85
Per Sandström, Prof.
Bergthor Bjornsson, MD
- Recruiting
Karolinska University Hospital
Stockholm, 14186
Ernesto Sparrelid, MD
Martin Delle, MD
Switzerland2 sites, 2 recruiting
- Recruiting
Claraspital & Clarunis University Hospital Basel
Basel, Canton of Basel-City, CH-4058
Otto Kollmar, Prof.
Bettina Woelnerhanssen
- Recruiting
Kantonsspital Winterthur (KSW)
Winterthur, 8401
Erik Schadde, MD
Sabine Kern
United States1 site, 1 recruiting
- Recruiting
Yale New Haven Hospital
New Haven, Connecticut, 06510
Kevin Billingsley
David Madoff
Australia1 site, 1 recruiting
- Recruiting
Monash Medical Centre
Clayton, Victoria, 3168
Diederick De Boo, PhD
Austria1 site, 1 recruiting
- Not yet recruiting
Social Medical Center, South
Vienna, State of Vienna, 1100
Thomas Gruenberger, MD
Tanja Friz, BSc
Italy1 site, 1 recruiting
- Recruiting
IRCCS San Raffaele Hospital
Milan
Luca Aldrighetti, Prof
Stephanie Steidler
About this study
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)
In the randomized controlled DRAGON 2 trial study subjects will be randomized between two arms, PVE alone (control group) and PVE/HVE (interventional group).
Read the 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
- Being tested
- Embolization
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EmbolizationProcedure or surgery
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
| Study group | Role | What they receive |
|---|---|---|
| Portal Vein Embolization (PVE) alone - (control arm) | Active comparator | Portal Vein Embolization (PVE) alone Receives: Procedure: Embolization |
| Combined Portal and Hepatic Vein Embolization (PVE/HVE) - (interventional arm) | Experimental | Combined Portal and Hepatic Vein Embolization (PVE/HVE) - (interventional arm) Receives: Procedure: Embolization |
What is being measured
The primary outcome is the main question the study is designed to answer.
Volume sufficient for resection at week 3 after the embolization
Volume sufficient for resection will be based on the first week or third week CT/MR Volumetry. Vauthey calculation for TLV will be used and the FLR volume will be measured centrally (objective panel)
Measured: 3 weeks
5-year Overall Survival
survival data will be recorded up to 5-years.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2022
- Study start1 Apr 2022
- Primary completion30 Jun 2026 (estimated)
- Study completion30 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal Cancer Liver Metastases (CRLM)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 1:1 Randomization between control and interventional group
- Masking
- None (open label)
- Enrolment
- 348 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Maastricht University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ronald M. van Dam, PhD, Principal investigator, Maastricht Universitair Medisch Centrum
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05428735
- Sponsor's protocol ID
- NL80303.068.22
- Acronym
- DRAGON 2
- Status last verified
- Sep 2024
- First submitted
- 1 Feb 2022
- Last updated
- 1 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Upon reasonable request
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05428735
- Acronym / sponsor ID
- DRAGON 2 / NL80303.068.22
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 348 participants (estimated)
- Lead sponsor
- Maastricht UniversityUniversity, hospital or other
- Study start
- 1 Apr 2022 (actual)
- Primary completion
- 30 Jun 2026 (estimated)
- Study completion
- 30 Jun 2029 (estimated)
- First posted
- 23 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 1:1 Randomization between control and interventional group
| Arm | Type | Receives |
|---|---|---|
| Portal Vein Embolization (PVE) alone - (control arm) | Active comparator | Procedure: EmbolizationPortal Vein Embolization (PVE) alone |
| Combined Portal and Hepatic Vein Embolization (PVE/HVE) - (interventional arm) | Experimental | Procedure: EmbolizationCombined Portal and Hepatic Vein Embolization (PVE/HVE) - (interventional arm) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EmbolizationPortal 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 | Procedure or surgery | Combined Portal and Hepatic Vein Embolization (PVE/HVE) - (interventional arm), Portal Vein Embolization (PVE) alone - (control arm) |
Primary outcome
Volume sufficient for resection at week 3 after the embolization
Time frame: 3 weeks
Volume sufficient for resection will be based on the first week or third week CT/MR Volumetry. Vauthey calculation for TLV will be used and the FLR volume will be measured centrally (objective panel)
5-year Overall Survival
Time frame: 5 years
survival data will be recorded up to 5-years.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2024.
- Individual participant dataSharing planned: Yes. Upon reasonable request
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PULSAR Combined With PD-1 Ab and Chemotherapy Plus Bev. for CRLM
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A Single-Arm, Phase II Study of Retlirafusp Alfa in Combination With XELOX and Bevacizumab for the First-Line Treatment of Advanced RAS-Mutated Colorectal Cancer With Liver Metastases (CRLM)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ronald M. van Dam, PhD principal investigator
Maastricht Universitair Medisch Centrum
24 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Embolization in people with Colorectal Cancer Liver Metastases (CRLM) and Small Future Liver Remnant (FLR), run by Maastricht University at 24 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in Netherlands, Canada, Belgium, Sweden, Switzerland and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sinéad James, MD, PhD-candidate (+31 638463945, sinead.james@mumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Volume sufficient for resection at week 3 after the embolization (time frame: 3 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2024.