Liver Transplantation for Hilar Cholangiocarcinoma in Association With Neoadjuvant Radio- and Chemo-therapy

Study Overview
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Brief Summary
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Single-arm pilot clinical trial. Patients with non operable CC associated with PSC will be subjected to liver transplantation after a neoadjuvant multimodal therapy protocol. Cholangiocarcinoma (CC) accounts for 3% of all gastrointestinal cancers; it is more frequent in patients with primary sclerosing cholangitis (PSC), who carry an 8%-12% risk of developing this type of neoplasm. Only a minority of patients are suitable for resection partly because of the anatomic position of the tumor (which often arises from the bile duct bifurcation) and partly because of the frequently coexisting liver disease. In fact, CC is currently considered a major contraindication to liver transplantation (OLT) at the majority of centers, given a 5-year survival rate of 0%-35%. New strategies have been developed for the treatment of this kind of cancer arising in PSC. The Nebraska University group showed a 1 and 3 years survival of 55 and 45 % combining a neoadjuvant intra bile duct barchytherapy and 5-FU based chemotherapy with liver transplantation. University of Pittsburg proposed also a neoadjuvant protocol prior to liver transplantation based on systemic chemotherapy and external radiotherapy reporting a 53% 5 years survival. More convincing results come from the Mayo Clinic. An accurate selection of patients and a proper neoadjuvant multimodal therapy (chemotherapy, external radiotherapy and intraluminal bile duct brachytherapy) lead to a 80% 5 years survival after liver transplantation.

Official Title
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Trapianto di Fegato Per Colangiocarcinoma (CCA) Ilare in Associazione a Radio e Chemioterapia Neoadiuvante

Conditions
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Hilar Cholangiocarcinoma, Primary Sclerosing Cholangitis

Intervention / Treatment
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* Procedure: Liver transplantation
* Radiation: 45 Gy external radiations
* Radiation: Endoluminal bile duct Brachytherapy
* Drug: Capecitabine
* Procedure: Pre liver transplantation laparoscopic hand assisted staging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Older than 18 years Male or female Diagnosis of Cholangiocarcinoma using: PTBD biopsy or Brushing cytology Ca 19-9>100mg/ml and/or liver mass at CT or MRI with malignant stenosis apperance at Cholangiography, Non resectable tumour araising above the cystic duct Absence of intra and extra hepatic metastasis ECOG score(Eastern Cooperative Oncology Group) 0 ASA score (American Society of Anesthesiologists) ≤ 3 Ability to understand and willingness to sign the written informed consent form (ICF) Exclusion Criteria: Intrahepatic Cholangiocarcinoma Non controlled infection Previous radio or chemotherapy Previsous bile duct resection or attempt to resection Intra and/or extrahepatic metastasis Preivious malignant neoplasm (within 5 years) Execution of trans peritoneal biopsy Tumour diameter more than 3 cm

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Procedure: Liver transplantation|Liver transplantation using classic technique and avoiding proximal ilum dissection. The donor hepatic artery will be anastomosed to a jump graft connected to the Aorta. In case of positive margin of the bile duct at a frozen section analysis the liver transplant will be performed after an adjunctive pancreatodudodenctomy|
|Radiation: 45 Gy external radiations|45 Gy in 30 fractions, 1,5 Gy twice a day) and 5-FU iv infusion- 3 week treatment|
|Radiation: Endoluminal bile duct Brachytherapy|Brachytherapy (20 Gy a 1 cm in 20-25h) - administered 2 weeks after radiotherapy completion|
|Drug: Capecitabine|Capecitabine - administered till liver transplantation|
|Procedure: Pre liver transplantation laparoscopic hand assisted staging|Pre liver transplantation laparoscopic hand assisted staging for sampling hepatic artery lymph nodes and assessing peritoneal disease.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients free of disease at 24 months post-transplant |  | 24 months | 
| Time to recurrence after liver transplant |  | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression disease free survival |  | 24 months | 
| Overall 2 years survival after liver transplantation |  | 24 months | 
| Complication rate due to radiotherapy (Hepatic artery thrombosis and Portal vein thrombosis) |  | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neoadjuvant radio- chemo-therapy, Liver transplantation