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

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.

Sex

All

Minimum age

18 Years

Maximum age

65 Years

Inclusion Criteria:

* Age 18 to 65 years at enrolment
* ECOG performance status 0 or 1
* Written informed consent before any study-related procedure
* Colorectal liver metastases stable for at least 6 months under active chemotherapy of no more than 2 lines
* Colorectal liver metastases not amenable to curative local treatment by resection or ablation because of insufficient liver capacity or future liver remnant, as judged by the local interdisciplinary tumour board
* For metachronous colorectal liver metastases: a colorectal primary resected in the past with T4a or lower and local R0 status
* For synchronous colorectal liver metastases: a potentially curatively resectable primary
* No evidence of peritoneal disease, as documented by a surgical report within the preceding 36 months
* Suitability for liver transplantation according to local centre criteria
* Participants of childbearing potential: negative highly sensitive pregnancy test before inclusion, and use of a contraceptive method with a failure rate below 1%, or confirmed post-menopausal status

Exclusion Criteria:

* Inability to give informed consent
* General contraindications to liver transplantation
* Large-vessel infiltration
* Extrahepatic disease, including lymph node involvement
* Listing for multi-organ transplantation
* Prior solid organ or bone marrow transplantation
* BRAF V600E mutation in the molecular pathology of the colorectal primary
* MSI-H/dMMR status in the molecular pathology of the colorectal primary
* Breastfeeding
* Institutionalisation by order of a court or public authority
* Dependence on the overall study lead, the investigator or the study site
* Participation in another clinical study with an investigational medicinal product or medical device