Embolization for Small Future Liver Remnant in Colorectal Cancer

(DRAGON 2 Trial)

Recruiting at 25 trial locations

Overseen By Jens Smits

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Maastricht University

Disqualifiers: Pregnancy, Non-resectable disease, Others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 3 weeks

348 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments for colorectal cancer that has spread to the liver. It compares Portal Vein Embolization (PVE) alone to a combined approach using both Portal and Hepatic Vein Embolization (PVE/HVE). The researchers aim to determine which method better prepares the liver for surgery by increasing the size of the healthy liver portion. This trial may suit individuals with colorectal cancer that cannot be easily removed by surgery and whose liver portion remains too small for surgery after chemotherapy. As an unphased trial, it provides a unique opportunity to explore innovative treatment options that could improve surgical outcomes.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combined portal and hepatic vein embolization (PVE/HVE) treatment is safe for patients. Earlier studies reported no deaths linked to the procedure, and complications were rare, indicating that most people tolerated the treatment well. The combination of these procedures aims to prepare the liver for surgery. Results demonstrated a high success rate in making previously inoperable cases ready for surgery. For those considering joining a trial, this evidence suggests that PVE/HVE is generally safe with manageable risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about embolization techniques for small future liver remnants in colorectal cancer because they offer a potentially more effective way to prepare the liver for surgery. Unlike traditional treatments that often rely on chemotherapy to shrink tumors, these techniques focus on manipulating blood flow to the liver. Portal Vein Embolization (PVE) alone redirects blood flow to encourage liver growth, while the combined Portal and Hepatic Vein Embolization (PVE/HVE) method may enhance this effect by involving both veins. This dual approach could lead to faster and more significant liver regeneration, making surgery a safer and more viable option for patients.

What evidence suggests that this trial's treatments could be effective for colorectal cancer?

Research has shown that combining two procedures, portal and hepatic vein embolization (PVE/HVE), is effective for patients with colorectal cancer that has spread to the liver. In this trial, participants will join either the PVE/HVE interventional arm or the PVE alone control arm. Studies indicate that PVE/HVE helps the liver regrow faster after surgery by enlarging the remaining part of the liver, enabling more patients to have their cancer removed safely. Specifically, one study found that this method is safe, with a low risk of complications and no procedure-related deaths. Overall, PVE/HVE offers a promising option for improving treatment outcomes for patients with liver cancer. ^{1 5 6 7 8}

Who Is on the Research Team?

Ronald M. van Dam, PhD

Principal Investigator

Maastricht Universitair Medisch Centrum

Are You a Good Fit for This Trial?

The DRAGON 2 trial is for adults with colorectal liver metastases (CRLM) where the remaining healthy liver is too small for safe surgery. Candidates must have potentially resectable or treatable lung/brain metastases and not be pregnant, breastfeeding, or unwilling to use contraception. Those with disease progression after chemotherapy or other hepatic malignancies are excluded.

Inclusion Criteria

My liver cancer can't be removed by surgery due to its size or my liver's condition.

My lung or brain cancer can be surgically removed or treated, as confirmed by a tumor board.

I am either a man or a woman.

Exclusion Criteria

My liver's shape or tumor location prevents certain liver vein treatments.

I am a premenopausal woman not using or willing to use birth control pills.

My cancer fully responded to the initial chemotherapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo either Portal Vein Embolization (PVE) alone or Combined Portal and Hepatic Vein Embolization (PVE/HVE) to induce liver hypertrophy

3 weeks

1 visit (in-person) for embolization procedure

Follow-up

Participants are monitored for liver volume and function, and overall survival is tracked

5 years

Regular follow-up visits as per study protocol

What Are the Treatments Tested in This Trial?

Interventions

• PVE alone
• PVE/HVE

Trial Overview This study compares two procedures in patients needing more healthy liver tissue before cancer surgery: Portal Vein Embolization (PVE), which redirects blood to grow healthy liver areas, and a combination of PVE with Hepatic Vein Embolization (HVE). Participants are randomly assigned to one of these two groups.

How Is the Trial Designed?

Group I: Combined Portal and Hepatic Vein Embolization (PVE/HVE) - (interventional arm) Experimental Treatment 1 Intervention

Combined Portal and Hepatic Vein Embolization (PVE/HVE) - (interventional arm)

Group II: Portal Vein Embolization (PVE) alone - (control arm) Active Control 1 Intervention

Portal Vein Embolization (PVE) alone

Who Is Running the Clinical Trial?

Maastricht University

Lead Sponsor

Trials

246

Recruited

13,190,000+

Published Research Related to This Trial

Liver venous deprivation (LVD) is a well-tolerated technique for patients undergoing liver surgery, showing similar overall survival and disease-free survival rates compared to the standard portal vein embolization (PVE) technique, with no significant differences in complication rates.

LVD resulted in a higher mean daily kinetic growth rate (0.2% vs. 0.1%) and a greater increase in future liver remnant volume (49% vs. 27%) compared to PVE, suggesting it may enhance liver regeneration more effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver Venous Deprivation Versus Portal Vein Embolization Before Major Hepatectomy for Colorectal Liver Metastases: A Retrospective Comparison of Short- and Medium-Term Outcomes. Cassese, G., Troisi, RI., Khayat, S., et al.[2023]

Salvage hepatic vein embolization (HVE) significantly increased the volume of the future liver remnant (FLR) in patients with metastatic colorectal cancer (mCRC) who had inadequate hypertrophy after initial portal vein embolization (PVE), with FLR increasing from a median of 0.16 to 0.26 after HVE.

This study involved 9 patients and demonstrated that HVE can be an effective technique to promote liver hypertrophy, making it a viable option for patients with small FLR volumes (<20%) who are undergoing treatment for mCRC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatic vein embolization after portal vein embolization to induce additional liver hypertrophy in patients with metastatic colorectal carcinoma. Niekamp, AS., Huang, SY., Mahvash, A., et al.[2020]

Simultaneous portal vein embolization (PVE) and hepatic vein embolization (HVE) is safe and effective, leading to sufficient growth of the future liver remnant (FLR) in six out of seven patients, allowing for potential surgical resection.

The study suggests that performing PVE before HVE is crucial, as it results in deeper glue penetration in the portal vein, reducing the risk of complications such as glue spillage due to decreased blood flow after HVE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined simultaneous embolization of the portal vein and hepatic vein (double vein embolization) - a technical note about embolization sequence. Najafi, A., Schadde, E., Binkert, CA.[2021]

In a study of 40 patients undergoing percutaneous portal vein embolization (PVE) for colorectal liver metastases, the procedure was technically successful in all cases, leading to adequate liver remnant hypertrophy in 57.5% of patients.

However, the study found a higher incidence of portal venous thrombosis (20%) following PVE compared to standard procedures, which could lead to complications such as portal hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Portal Vein Embolization in the Setting of Staged Hepatectomy with Preservation of Segment IV ± I Only for Bilobar Colorectal Liver Metastases: Safety, Efficacy, and Clinical Outcomes. Cassinotto, C., Dohan, A., Gallix, B., et al.[2017]

Portal vein embolization (PVE) can stimulate liver growth even in patients undergoing concurrent chemotherapy for colorectal cancer, with similar growth rates observed compared to those not on chemotherapy.

Patients who underwent PVE before extended liver resection experienced improved recovery outcomes, including reduced need for fresh frozen plasma, lower peak bilirubin levels, and shorter hospital stays, without an increase in mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined portal vein embolization and neoadjuvant chemotherapy as a treatment strategy for resectable hepatic colorectal metastases. Covey, AM., Brown, KT., Jarnagin, WR., et al.[2022]

In a study of 97 hepatocellular carcinoma (HCC) patients undergoing portal vein embolization (PVE) before hepatectomy, 32.4% could not proceed to surgery, with a significantly higher dropout rate in patients with liver damage B (61.5%) compared to those with liver damage A (26.2%).

Patients with liver damage B experienced significantly worse long-term outcomes after hepatectomy, with a 5-year overall survival rate of only 23.1% compared to 74.6% for those with liver damage A, suggesting that PVE followed by hepatectomy may not be advisable for patients with impaired liver function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is Portal Vein Embolization Followed by Hepatectomy for Hepatocellular Carcinoma Justified in Patients with Impaired Liver Function? Imai, K., Yamashita, YI., Nakao, Y., et al.[2021]

The study investigates a new procedure called liver venous deprivation (LVD), which combines portal vein embolization (PVE) and hepatic vein embolization (HVE) in a single intervention to enhance liver regeneration before surgery, potentially leading to better outcomes for patients with colorectal liver metastases.

In a randomized phase II trial involving 64 patients, the primary goal is to measure the percentage change in future liver remnant (FLR) volume at 3 weeks post-procedure, with LVD expected to show a significant increase in FLR compared to PVE alone, thereby improving the chances of successful liver resection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study protocol of the HYPER-LIV01 trial: a multicenter phase II, prospective and randomized study comparing simultaneous portal and hepatic vein embolization to portal vein embolization for hypertrophy of the future liver remnant before major hepatectomy for colo-rectal liver metastases. Deshayes, E., Piron, L., Bouvier, A., et al.[2021]

Liver venous deprivation (LVD) effectively increased the future liver remnant (FLR) ratio in 12 patients with colorectal liver metastasis, from an average of 28.7% to 42.2%, indicating successful hypertrophy after treatment.

The procedure was safe, with no severe complications reported, and allowed 10 out of 12 patients to proceed to surgery within about 39 days, demonstrating its efficacy in preparing patients for liver resection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous liver venous deprivation: outcomes in heavily pretreated metastatic colorectal cancer patients. Ghosn, M., Kingham, TP., Ridouani, F., et al.[2022]

Simultaneous right portal vein embolization (PVE) and radiofrequency ablation (RFA) of left liver metastases was successfully performed in 5 patients, allowing for effective control of left-sided tumors during liver regeneration after PVE.

The procedure showed promising results with no tumor growth at the RFA site before surgery and complete tumor sterilization in histological assessments, although one patient experienced acute liver failure postoperatively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous percutaneous right portal vein embolization and left liver tumor radiofrequency ablation prior to a major right hepatic resection for bilateral colorectal metastases. Elias, D., Santoro, R., Ouellet, JF., et al.[2006]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2666776225000766

Safety and efficacy of combined portal and hepatic vein ... DRAGON 1 demonstrates that PVE/HVE is safe, with no embolization-related mortality, low morbidity, and high resection rates in upfront unresectable CRLM.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10806199/

A systematic review and meta-analysis of liver venous ... This systematic review and meta-analysis concluded that LVD was associated with higher future liver remnant (FLR) volume after embolization, ...

3. jvir.org jvir.org/article/S1051-0443(24)00620-1/fulltext

Liver Vein Deprivation versus Portal Vein Embolization Liver vein deprivation appears to be safe and superior to portal vein embolization in inducing future liver remnant (FLR) hypertrophy in terms ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7826613/

Oncological Outcomes after Liver Venous Deprivation for ... The authors report for the first time the oncological outcomes of Liver Venous Deprivation (LVD) for Colorectal Liver Metastases.

5. sciencedirect.com sciencedirect.com/science/article/pii/S1365182X21014568

outcomes in heavily pretreated metastatic colorectal cancer ... In heavily pretreated patients, LVD safely stimulated a rapid and effective FLR hypertrophy, with a resultant high rate of resection.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9458562/

Dragon 1 Protocol Manuscript - PubMed Central - NIH The DRAGON 1 trial aims to assess training, implementation, safety and feasibility of combined portal- and hepatic-vein embolization (PVE/HVE) ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1365182X25005763

First results from the international registry on liver venous ... The aim of this retrospective study was to review the effect of additional HVE with PVE on the liver hypertrophy response in a cohort of patients who underwent ...

8. ahpba.org ahpba.org/wp-content/uploads/2023/07/Heil_BJS-2021_Preoperative-portal-vein-or-portal-and-hepatic-vein-embolization_DRAGON-collaborative-group-analysis.1.pdf

DRAGON collaborative group analysis PVE/HVE: simultaneous portal vein embolization (PVE) and hepatic vein embolization (HVE); FLR, future liver remnant; sFLR, standardized FLR ...