Liver Transplantation for Non-resectable Perihilar Cholangiocarcinoma

  • STATUS
    Recruiting
  • End date
    May 31, 2045
  • participants needed
    15
  • sponsor
    Oslo University Hospital
Updated on 13 August 2021

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.

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.

Details
Condition Bile duct carcinoma, Cholangiocarcinoma, Klatskin's Tumor, Biliary neoplasm, Perihilar Cholangiocarcinoma, cancer of the bile duct, klatskin tumor
Treatment Liver Transplant
Clinical Study IdentifierNCT04993131
SponsorOslo University Hospital
Last Modified on13 August 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Radiologically strong suspicion of pCCA
Tumor can involve intrahepatic portal vein without thrombosis of extrahepatic portal vein
Tumor can involve hepatic artery distal to gastroduodenal artery or involve replaced hepatic artery
First time pCCA
Disease deemed not eligible for liver resection based on tumor location or underlying liver dysfunction
No extrahepatic disease, or lymph node involvement detected on imaging
No signs of extrahepatic metastatic disease according to PET-CT scan
No signs of extrahepatic metastatic disease according to CT or MR (chest/abdomen/pelvis) scan within 4 weeks prior to the faculty meeting at the transplant unit
At least 18 years of age
Good performance status, Eastern Cooperative Oncology Group (ECOG) score: 0 or 1
Satisfactory blood tests Hb >10g/dl, neutrophiles >1.0 (after any G-CSF), TRC >50, Bilirubin<3 x upper normal level, ASAT, ALAT<5 x upper normal level, Creatinine <1.5 x upper normal level. Albumin above lower normal level, Normal IgG4 levels
Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to GCP, and national/local regulations
Received chemotherapy for at least 6 months with at least 10% response according ti RECIST criteria and with no progression of disease at time of Lt
At least 10 months from diagnosis
Patient must be accepted for transplantation before progressive disease
Twelve months or more time span from the diagnosis of pCCA and date of being listed for liver transplantation

Exclusion Criteria

Tumor involving common hepatic artery, celiac trunck or superior mesenteric artery the tumor
Tumor involving main portal vein
Tumor involving inferior vena cava
Perforation of the visceral peritoneum
Weight loss >15% the last 6 months
Patient BMI > 30
Other malignancies, except curatively treated more than 5 years ago without relapse
Known history of human immunodeficiency virus (HIV) infection
Prior history of solid organ or bone marrow transplantation
Substance abuse, medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
Known hypersensitivity to rapamycin
Prior extrahepatic metastatic disease
Women who are pregnant or breast feeding
Any reason why, in the opinion of the investigator, the patient should not participate
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