Liver Transplantation for Non-Resectable Colorectal Liver Metastases Without Local Treatment Options

Condition(s) studied

Investigational drug(s) / intervention(s)

Liver transplantation: Orthotopic liver transplantation with a full or split graft from a deceased donor allocated by Eurotransplant under a study-specific ReMELD-Na Standard Exception, or from a living donor where evaluated as suitable by the participating centre. Staged hepatectomy techniques are not permitted. Machine perfusion may be used for graft assessment and preservation in accordance with the German guidelines for organ transplantation. Systemic chemotherapy continues until transplantation, excluding anti-EGFR antibodies, anti-VEGF antibodies and checkpoint inhibitors. Immunosuppression and perioperative care follow local site protocols; post-transplant chemotherapy is resumed at the discretion of the local tumour board and is not a study-specific intervention. Re-transplantation may be requested from Eurotransplant for primary non-function or surgical complications where the recipient meets the criteria of the German guidelines.

Study summary

Patients whose colorectal cancer has spread to the liver, and whose liver metastases cannot be removed by surgery or destroyed by ablation, currently receive palliative chemotherapy in Germany. Fewer than one in ten of these patients survive five years. International studies have shown that replacing the whole liver by transplantation can achieve much longer survival in carefully selected patients, because removing the entire liver removes all of the tumour when the disease is confined to it. The TransMet trial reported five-year survival of 57% with transplantation plus chemotherapy, compared with 13% for chemotherapy alone. This approach is not yet available in German routine care, where liver transplantation for this indication is permitted only within a clinical study.

GTO-001 will enrol approximately 260 adults aged 18 to 65 years with colorectal liver metastases that are confined to the liver, that cannot be removed or ablated, and that have remained stable or improved for at least six months on chemotherapy. Every participant is assessed by a newly established National Tumor Board for Transplant Oncology, which meets monthly, reviews the imaging and case independently of the local centre, and decides whether the patient may be listed for transplantation. Patients who are approved are listed with a study-specific priority status, continue their chemotherapy while they wait, and undergo a surgical inspection of the abdomen at the start of the transplant operation to confirm that the cancer has not spread outside the liver. Participants who are not listed, or in whom transplantation is not performed, remain in the study and are followed in the same way.

The main question is how many patients are alive five years after transplantation. The study also measures how many of the patients assessed are eventually listed and transplanted, how many leave the waiting list because their disease progresses or becomes operable, survival after each of the treatments patients actually receive, how well the transplanted livers function, and complications after surgery. Because the study follows everyone who is assessed, it will also establish for the first time how many patients in Germany genuinely qualify for this treatment. Participants are followed for five years after transplantation; the study runs until 2036.

Eligibility

Primary outcome measure(s)

• Overall survival at 5 years after liver transplantation — 60 months after liver transplantation
  Proportion of transplanted participants alive 5 years after liver transplantation, estimated by the Kaplan-Meier method with a two-sided 95% confidence interval, in the transplant cohort (participants transplanted after approval by the National Tumor Board and without study-specific contraindications at the time of transplantation). Time origin is the date of transplantation; the event is death from any cause; participants with missing survival information from a given visit onwards are censored at the last completed follow-up visit. Higher values indicate better outcome. The study is designed to demonstrate 5-year survival above 50%, equivalent to median survival exceeding 5 years.

Trial sites (1)

More Charite University, Berlin, Germany trials in Germany

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