Live Donor Liver Transplantation for Colorectal Cancer Liver Metastases

Overseen By Erin Winter, BSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Must be taking: Chemotherapy

Disqualifiers: Previous cancer, Cardiac disease, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores live donor liver transplantation (LDLT) for patients with colorectal cancer that has spread to the liver and cannot be surgically removed. The researchers aim to determine if LDLT can improve survival and quality of life compared to patients who do not undergo the transplant. Participants must have liver metastases stable on chemotherapy and a healthy, willing donor. This trial targets individuals in Canada with colorectal cancer confined to the liver who have shown stability or improvement during recent chemotherapy. As an unphased trial, it offers patients the chance to contribute to groundbreaking research that could lead to new treatment options.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, since participants must have stable liver metastases on standard chemotherapy, it seems likely that continuing your current chemotherapy regimen is required.

What prior data suggests that live donor liver transplantation is safe for patients with colorectal cancer liver metastases?

Research has shown that live donor liver transplantation (LDLT) is generally safe for patients with colorectal cancer that has spread to the liver. Studies indicate that LDLT is a good option for patients whose cancer remains confined to the liver.

Reports suggest that LDLT is both safe and effective for these patients. Although any surgery carries risks, LDLT remains a viable choice for those stable on standard chemotherapy.

Importantly, LDLT is considered a safe procedure overall and may offer significant survival benefits compared to other treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for colorectal cancer liver metastases, such as chemotherapy, targeted therapy, or surgical resection, live donor liver transplantation offers a fresh approach by replacing the entire diseased liver with a healthy one from a living donor. This method is particularly promising for cases where the cancer is deemed unresectable, meaning it can't be removed surgically due to its size, location, or spread within the liver. Researchers are excited because this approach could potentially eliminate extensive cancerous tissue and offer patients a new liver that's free of cancer, possibly leading to better long-term outcomes and survival rates compared to traditional therapies.

What evidence suggests that live donor liver transplantation might be an effective treatment for colorectal cancer liver metastases?

Research has shown that liver transplants can improve outcomes for patients with colorectal cancer that has spread to the liver and cannot be surgically removed. Studies have found that individuals receiving a liver transplant for this condition often live longer and remain cancer-free longer than those receiving only chemotherapy. For patients whose liver tumors can be surgically removed, surgery offers a 5-year survival rate of about 40-50%. However, those unable to undergo surgery generally face much lower survival rates. In this trial, participants will receive liver transplants from living donors, which have demonstrated promising results in enhancing overall survival and extending the time free from cancer progression. This option might be valuable when other treatments fail. ^{2 3 4 5 6}

Who Is on the Research Team?

Gonzalo Sapisochin, MD

Principal Investigator

University Health Network, Toronto

Are You a Good Fit for This Trial?

This trial is for Canadian residents with colorectal cancer that has spread to the liver and can't be removed by surgery. Participants need a willing, compatible living donor for liver transplant, stable or improving cancer markers on chemotherapy, and good physical function (ECOG score 0-1). Pregnant women and those not using birth control are excluded.

Inclusion Criteria

I have been treated with chemotherapy for at least 3 months.

My liver metastases have not worsened in the past 3 months.

My liver metastases cannot be surgically removed and are in both lobes.

Exclusion Criteria

My kidneys are not working well, with a low creatinine clearance rate.

I have a history of heart disease.

I do not have severe nerve pain or damage.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neo-adjuvant Chemotherapy

Participants receive standard chemotherapy to stabilize liver metastases before transplantation

Varies based on individual response

Living Donor Liver Transplantation

Eligible participants undergo living donor liver transplantation

Surgical procedure with immediate post-operative care

Follow-up

Participants are monitored for survival, disease-free survival, and quality of life

5 years

Regular follow-up visits at 6-month intervals

What Are the Treatments Tested in This Trial?

Interventions

• Live Donor Liver Transplantation

Trial Overview The study tests live donor liver transplantation in patients whose colorectal cancer has spread only to the liver and isn't getting worse on standard chemo. It compares survival rates of these patients post-transplant against those who leave the study before receiving a transplant.

How Is the Trial Designed?

Group I: transplantation Experimental Treatment 1 Intervention

Live donor liver transplantation for the treatment of unresectable colorectal cancer liver metastases

Live Donor Liver Transplantation is already approved in United States, European Union for the following indications:

Approved in United States as LDLT for:

• Unresectable colorectal cancer liver metastases

Approved in European Union as LDLT for:

• Unresectable colorectal cancer liver metastases

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Published Research Related to This Trial

Living donor liver transplantation (LDLT) is a promising solution to the shortage of deceased donor organs, but its adoption in the U.S. is still limited due to various barriers.

Key barriers include a lack of awareness and engagement among patients and providers, data gaps in donor and candidate selection, and insufficient information on post-donation outcomes, which can be addressed through education, research, and institutional support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Living donor liver transplant candidate and donor selection and engagement: Meeting report from the living donor liver transplant consensus conference. Jesse, MT., Jackson, WE., Liapakis, A., et al.[2023]

Living donor liver transplantation (LDLT) is a promising alternative to deceased donor transplantation for treating early malignant hepatic tumors, especially when patients cannot undergo tumor resection due to poor liver function or when cadaveric grafts are not available in a timely manner.

The review emphasizes the need for careful selection of candidates for LDLT based on tumor characteristics and staging, as well as the potential development of new immunosuppressors that could enhance anti-tumor effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Present status and recent advances in living donor liver transplantation for malignant hepatic tumors. Qin, JM., Takada, Y., Uemoto, S., et al.[2008]

In a study of 139 patients who underwent living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC) at the University of Tokyo Hospital, the 1-, 5-, and 10-year patient survival rates were 91%, demonstrating the efficacy of LDLT for HCC within the expanded Tokyo criteria.

The study found that high levels of alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP), as well as exceeding the Tokyo criteria, were significant predictors of HCC recurrence, highlighting the importance of these biomarkers in assessing patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Living donor liver transplantation for hepatocellular carcinoma at the University of Tokyo Hospital. Togashi, J., Akamastu, N., Kokudo, N.[2022]

In a study of 50 living donor liver transplantations in Egypt, there were no donor fatalities, and major complications occurred in only 10% of cases, indicating a high level of safety for donors.

Donors experienced a quick recovery, returning to their normal activities within 6 to 8 weeks, and no liver impairment was observed during the 6-month follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Donor outcomes in right lobe adult living donor liver transplantation: single-center experience in Egypt. Esmat, G., Yosry, A., El-Serafi, M., et al.[2005]

In a study of 81 patients with unresectable colorectal liver metastases, those who underwent living donor liver transplantation (LDLT) showed significantly better recurrence-free survival compared to those who continued with systemic chemotherapy, highlighting the potential efficacy of LDLT in selected patients.

While overall survival rates were similar between the LDLT and resected groups, the LDLT group had a much higher rate of remaining cancer-free at one and three years, suggesting that LDLT may be a promising option for patients who meet specific criteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toronto Management of Initially Unresectable Liver Metastasis from Colorectal Cancer in a Living Donor Liver Transplant Program. Rajendran, L., Claasen, MP., McGilvray, ID., et al.[2023]

Living donor liver transplantation (LDLT) significantly reduces waitlist mortality and offers excellent long-term outcomes for patients with end-stage liver disease, yet its use in the US remains limited.

A consensus conference identified cultural beliefs and behaviors as major barriers to expanding LDLT, emphasizing the need for education and engagement to shift perceptions and promote LDLT as the preferred option for liver transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Living donor liver transplantation: A multi-disciplinary collaboration towards growth, consensus, and a change in culture. Liapakis, A., Jesse, MT., Pillai, A., et al.[2023]

Live-donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC) shows similar long-term survival outcomes compared to deceased-donor liver transplantation (DDLT), despite LDLT patients often having more advanced tumors outside Milan criteria.

Patients receiving LDLT had a shorter wait time for transplantation (173 days) compared to those receiving DDLT (219 days), indicating a potential advantage in timely treatment for HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Living Donor Liver Transplantation for Hepatocellular Carcinoma: It Is All about Donors? Saidi, RF., Li, Y., Shah, SA., et al.[2021]

The study involved 65 living donor liver transplant procedures, primarily from mothers to their children, demonstrating that living donor hepatectomy can be performed safely with a 30% complication rate, mostly minor, and no reported mortality.

The median operative time was 374 minutes, which improved over time, and the median hospital stay was 7 days, indicating that while LDLT is complex, it can yield acceptable outcomes for donors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Living donor liver transplantation in South Africa: the donor experience. Botha, J., Ströbele, B., Loveland, J., et al.[2020]

Living donor liver transplantation (LDLT) using the left lobe (LL) has become more common, with a notable increase in procedures from an average of 5.2 per year (1998-2003) to 19.4 per year (2004-2010).

However, recipients of LL-LDLT experienced significantly lower allograft survival rates and higher retransplantation rates compared to those receiving right lobe (RL) LDLT, indicating that LL-LDLT may carry higher risks for graft failure and patient survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is left lobe adult-to-adult living donor liver transplantation ready for widespread use? The US experience (1998-2010). Saidi, RF., Jabbour, N., Li, Y., et al.[2022]

In a study of 80 live donors who underwent right hepatectomy over an 11-year period, there were no reported deaths, highlighting the safety of live-donor liver transplantation (LDLT).

While 21.2% of donors experienced complications, only 8.7% were classified as major, and most complications were manageable, indicating that LDLT is a feasible option to address the shortage of cadaveric donors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Living-donor liver transplantation: donor selection criteria and postoperative outcomes. A single-center experience with a 10-year follow-up. Lauterio, A., Poli, C., Cusumano, C., et al.[2013]

Living donor liver transplantation (LDLT) is a safe and effective alternative to deceased donor liver transplantation (DDLT) in Egypt, where DDLT is not yet available, as demonstrated by a study of 500 consecutive LDLT cases primarily involving patients with chronic hepatitis C virus (HCV) infection.

The study reported a 1-year survival rate of 80.9% and identified several independent predictors of overall survival, including preoperative creatinine levels and postoperative complications, highlighting the importance of experienced medical teams in performing LDLT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Living-Donor Liver Transplantation in Hepatitis C Virus Era: A Report of 500 Consecutive Cases in a Single Center. Wahab, MA., Shehta, A., Elshoubary, M., et al.[2018]

In a study of 117 patients who underwent living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC), those within Milan criteria had a high 5-year recurrence-free survival (RFS) rate of 88%, even when poor prognostic factors were present.

For patients outside Milan criteria, the presence of two or more poor prognostic factors significantly reduced their RFS, highlighting the need for careful evaluation in this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Living Donor Liver Transplantation for Hepatocellular Carcinoma: A Single-Center Experience from Pakistan. Bhatti, ABH., Dar, FS., Qureshi, AI., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02864485

Living Donor Liver Transplantation for Unresectable ... Surgery offers a distinct survival advantage: the 5-year survival after liver resection for LM is around 40-50% in most studies versus 10-20% 5-year survival ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35353121/

Recipient and Donor Outcomes After Living-Donor Liver ... This study's findings of recurrence-free and overall survival rates suggest that select patients with unresectable, liver-confined CRLMs may benefit from total ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1600613523006895

Living donor liver transplantation for colorectal cancer ... The presence of colorectal liver metastasis (CRLM) remains the strongest predictor of survival, and resection can offer a chance of cure with a 5-year survival ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11753392/

Liver transplantation for colorectal cancer with liver ... Liver transplantation for colorectal cancer with unresectable liver metastases is associated with longer progression-free and OS compared with chemotherapy ...

5. mayoclinic.org mayoclinic.org/medical-professionals/transplant-medicine/news/liver-transplantation-for-patients-with-colorectal-liver-metastases/mac-20576145

Liver transplantation for patients with colorectal liver ... Liver transplant can offer significantly improved outcomes for patients with colorectal liver metastases and is an important option when other therapies are ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37805187/

Living donor liver transplantation for colorectal cancer ... LDLT is a safe and effective alternative for patients with CRLM who do not have progressive disease or extrahepatic metastasis. Keywords: ...