Live Donor Liver Transplantation for Colorectal Cancer Liver Metastases

Recruiting in Toronto (>99 mi)

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

Trial Summary

What is the purpose of this trial?

Patients with unresectable liver metastases (LM) from colorectal cancer (CRC)have a poor prognosis. In patients with resectable disease, surgery offers a distinct survival benefit. This study will offer live donor liver transplantation (LDLT) to select patients with unresectable metastases that are 1) limited to the liver and 2) stable (non-progressing) on standard chemotherapy. Potential participants will be evaluated for liver transplant suitability and must also have a willing, healthy living donor come forward for evaluation. Those participants who undergo LDLT will be followed for survival, disease-free survival and quality of life for 5 years and compared to a "control group" of participants who drop out of study prior to transplantation due to reasons other than cancer progression.

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 data supports the effectiveness of the treatment Live Donor Liver Transplantation for colorectal cancer liver metastases?

Living donor liver transplantation (LDLT) has shown excellent long-term outcomes for end-stage liver disease and is increasingly used for treating liver tumors, including colorectal cancer liver metastases, although it is not widely available outside study protocols. It is considered a promising option due to its success in reducing waitlist mortality and providing good outcomes for other liver conditions. ^{1 2 3 4 5}

Is live donor liver transplantation generally safe for humans?

Living donor liver transplantation (LDLT) is generally considered safe, with studies emphasizing donor safety as a priority. Research from various centers shows that LDLT is a viable alternative to deceased donor liver transplantation, with careful evaluation and management of surgical complications to ensure donor well-being. ^{6 7 8 9 10}

How is the treatment Live Donor Liver Transplantation different from other treatments for colorectal cancer liver metastases?

Live Donor Liver Transplantation (LDLT) is unique because it involves transplanting a portion of a healthy liver from a living donor to a patient with colorectal cancer liver metastases, offering a potential option when tumors are not removable by surgery. This approach is particularly valuable in overcoming the shortage of deceased donor organs and is not widely available outside of study protocols. ^{1 4 9 11 12}

Research Team

Gonzalo Sapisochin, MD

Principal Investigator

University Health Network, Toronto

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

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]

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]

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]

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]

References

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

Toronto Management of Initially Unresectable Liver Metastasis from Colorectal Cancer in a Living Donor Liver Transplant Program. [2023]

2. India pubmed.ncbi.nlm.nih.gov

Living Donor Liver Transplantation for Hepatocellular Carcinoma: A Single-Center Experience from Pakistan. [2022]

3. Denmark 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. [2023]

4. Singapore pubmed.ncbi.nlm.nih.gov

Present status and recent advances in living donor liver transplantation for malignant hepatic tumors. [2008]

5. Denmark pubmed.ncbi.nlm.nih.gov

Living donor liver transplantation: A multi-disciplinary collaboration towards growth, consensus, and a change in culture. [2023]

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

Donor outcomes in right lobe adult living donor liver transplantation: single-center experience in Egypt. [2005]

7. United States 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. [2013]

8. South Africa pubmed.ncbi.nlm.nih.gov

Living donor liver transplantation in South Africa: the donor experience. [2020]

9. China (Republic : 1949- ) pubmed.ncbi.nlm.nih.gov

Living donor liver transplantation for hepatocellular carcinoma at the University of Tokyo Hospital. [2022]

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

Living-Donor Liver Transplantation in Hepatitis C Virus Era: A Report of 500 Consecutive Cases in a Single Center. [2018]

11. Iran pubmed.ncbi.nlm.nih.gov

Living Donor Liver Transplantation for Hepatocellular Carcinoma: It Is All about Donors? [2021]

12. England pubmed.ncbi.nlm.nih.gov

Is left lobe adult-to-adult living donor liver transplantation ready for widespread use? The US experience (1998-2010). [2022]