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

Summary

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.

Conditions

• Hilar Cholangiocarcinoma
• Primary Sclerosing Cholangitis

Interventions

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.

Sponsors & Collaborators

• Azienda Ospedaliera di Padova

  lead OTHER

Principal Investigators

• Umberto Cillo, MD · Azienda Ospedaliera di Padova

• Enrico Gringeri, MD · Azienda Ospedaliera di Padova

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-01-31

Primary Completion

2013-07-31

Countries

• Italy

Study Locations