Embolization for Small Future Liver Remnant in Colorectal Cancer

(DRAGON 2 Trial)

Recruiting in Hamilton (>99 mi)

+23 other 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

Trial Summary

What is the purpose of this trial?

In the randomized controlled DRAGON 2 trial study subjects will be randomized between two arms, PVE alone (control group) and PVE/HVE (interventional group).

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.

What data supports the effectiveness of this treatment for small future liver remnant in colorectal cancer?

Research shows that portal vein embolization (PVE) is effective in helping the liver grow before surgery, which can prevent liver failure. Combining PVE with hepatic vein embolization (HVE) in a single procedure, known as liver venous deprivation (LVD), may lead to better liver growth compared to PVE alone. ^{1 2 3 4 5}

Is embolization for small future liver remnant in colorectal cancer safe?

Research shows that portal vein embolization (PVE) and combined portal and hepatic vein embolization (LVD) are generally safe procedures. They have been used to help the liver grow before surgery, with studies indicating they are feasible and safe for patients with liver metastases. ^{1 2 5 6 7}

How does embolization for small future liver remnant in colorectal cancer differ from other treatments?

This treatment is unique because it combines portal vein embolization (PVE) and hepatic vein embolization (HVE) to promote faster and more effective growth of the future liver remnant (FLR) before surgery, compared to PVE alone. This simultaneous approach, known as liver venous deprivation (LVD), aims to optimize liver preparation and improve surgical outcomes for patients with colorectal cancer liver metastases. ^{1 2 6 8 9}

Research Team

Ronald M. van Dam, PhD

Principal Investigator

Maastricht Universitair Medisch Centrum

Eligibility Criteria

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 18 years old or older.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Combined portal vein embolization and neoadjuvant chemotherapy as a treatment strategy for resectable hepatic colorectal metastases. [2022]

3. United States 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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Percutaneous liver venous deprivation: outcomes in heavily pretreated metastatic colorectal cancer patients. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Is Portal Vein Embolization Followed by Hepatectomy for Hepatocellular Carcinoma Justified in Patients with Impaired Liver Function? [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Combined simultaneous embolization of the portal vein and hepatic vein (double vein embolization) - a technical note about embolization sequence. [2021]

7. United States 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. [2017]

8. Greece 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. [2006]

9. Germany pubmed.ncbi.nlm.nih.gov

Hepatic vein embolization after portal vein embolization to induce additional liver hypertrophy in patients with metastatic colorectal carcinoma. [2020]