Liver Transplantation for Non-resectable Perihilar Cholangiocarcinoma
- Conditions
- Perihilar CholangiocarcinomaBile Duct CancerKlatskin Tumor
- Interventions
- Procedure: Liver transplant
- Registration Number
- NCT04993131
- Lead Sponsor
- Oslo University Hospital
- Brief Summary
The study will investigate whether liver transplantation provides increased survival, low side effects and good quality of life in patients with bile duct cancer where the tumor cannot be removed by normal surgery. Analyzes of blood and tissue samples from the tumor will be investigated to see if the analyzes can indicate who may have recurrence of the disease after liver transplantation. Furthermore, the effect of chemotherapy on normal liver and tumor tissues in the liver that are removed during transplantation will be investigated.
- Detailed Description
Liver transplantation (Lt) is an established method of treatment for acute and chronic liver failure. One and five- year survival after Lt is approximately 90% and 80%, respectively. Currently, Lt is a treatment option for selected patients with primary carcinomas in the liver and in patients with liver metastases from neuroendocrine tumors. The prerequisite is that there is no extra-hepatic tumor growth and that the primary tumor is removed. Lt for cancer comprises of 14% of all Lts in Europe (www.etlr.org). Types of primary carcinomas eligible for transplantation today include hepatocellular carcinoma (HCC), hepatoblastoma, hemangioendothelioma, and perihilar cholangiocarcinoma (pCCA), the latter in clinical protocols. The most common secondary hepatocarcinomas are neuroendocrine tumours (carcinoid tumours and gastrinomas). The International Registry of Hepatic Tumors in Liver Transplantation show that survival of HCC patients after transplantation is above 70% and 60% at 1 and 5 years, respectively. Recent studies on HCC and liver transplantation have shown even better results when patients are treated with an immunosuppressive regimen containing the antiproliferative agent rapamycin. For hepatoblastoma (children) and malign hemangioendotheliaoma the five-year survival is between 50-60% and for intestinal sarcomas and neuroendocrine tumours it is approximately 35-40%. In patients transplanted for pCCA using a multimodal approach utilizing neoadjuvant radiation, chemotherapy and liver transplantation (Mayo protocol) 5-year patient survival of \>80% in selected patients compared to a corresponding 21% five-year survival in liver resection.
Malignancy of the biliary tree (cholangiocarcinoma, CCA) is a rare cancer with an annual incidence around 150 cases in Norway. Cholangiocarcinoma can be subdivided into distal, perihilar, and intrahepatic according to their anatomical location5. Although rare, intrahepatic cholangiocarcinoma (iCCA) constitutes the second most common primary liver cancer after hepatocellular carcinoma, and the worldwide incidence of iCCA is increasing. Despite improvements in multidisciplinary management, patients with CCA have a poor outcome and only 20% of patients are eligible for surgical resection, with 5-year overall survival of less than 10% for all patients. The only potentially curative treatment option is surgical resection with complete excision of tumor with negative margins.
An Irish study with liver transplantation for patients with unresectable hilar CCA who received neoadjuvant chemoradiotherapy had 1- , 3- and 5-year survival of 81%, 69% and 62% respectively, of the transplanted patients. We have recently started a prospective exploratory study, TESLA trial, investigating Lt in non-resectable iCCA with stable disease on oncological treatment.
Building on these results in addition to our own experience with liver transplantation for non-resectable colorectal liver metastases, we want to investigate in the TESLA-II trial the role of Lt in selected patients with unresectable pCCA, who fulfill the inclusion criteria.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 15
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Liver transplant Liver transplant The patients will be transplanted according to standard procedures by the institutional protocol. Median time of surgery is 7 hours and 20 minutes. Each surgical procedure will be performed by specialists at the Rikshospitalet liver transplantation team, which consists of seven specialists at the unit. The transplantation procedure is initiated by an exploratory laparotomy with clinical assessment and frozen section of the lymphnodes in the hepatoduodenal ligament and along the common hepatic artery/coeliac axis. Complete clearance of the lymphatic tissue around the hepatoduodenal ligament. Frozen section is obtained from the distal end of the common bile duct. Evidence of disease dissemination to these regional lymph nodes will be an absolute contraindication to transplantation.
- Primary Outcome Measures
Name Time Method Overall survival From screening and until 36 months after inclusion Patient record
- Secondary Outcome Measures
Name Time Method Diagnosis of other malignancies Up to 10 years after liver transplantation Patient record
Overall survival from time of relapse From time of relapse and until 36 months after inclusion Patient record
Time to start of new treatment/change in strategy Immediately after liver transplatation to start of new treatment Patient record
Survival in relation to biological markers After Liver Transplant until 10 years after liver transplantation CA19-9, CEA
Disease free survival After liver transplantation and up 10 years after liver transplantation CT-scan/MRI scan according to RECISTcriteria
Complication according to Clavien-Dindo grad 3-5 Up to 90 days after liver transplantation Patient record
Quality of life (EORTC QLQ-C30), time to decrease in physical function and global health score Up to 10 years after liver transplantation Quality of life measured by EORTC QLQ-C30
Trial Locations
- Locations (1)
Oslo university hospital
🇳🇴Oslo, Norway