Clinical trial NCT01549795: Liver Transplantation for Hilar Cholangiocarcinoma in Association With Neoadjuvant Radio- and Chemo-therapy
Official title: Trapianto di Fegato Per Colangiocarcinoma (CCA) Ilare in Associazione a Radio e Chemioterapia Neoadiuvante
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Hilar Cholangiocarcinoma
Primary Sclerosing Cholangitis
Keywords: Liver transplantation
Neoadjuvant radio- chemo-therapy
Lead sponsor: Azienda Ospedaliera di Padova
Sponsor class: OTHER
First posted: 2012-03-09
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of patients free of disease at 24 months post-transplant
timeFrame: 24 months
measure: Time to recurrence after liver transplant
timeFrame: 24 months
Secondary outcomes:
measure: Progression disease free survival
timeFrame: 24 months
measure: Overall 2 years survival after liver transplantation
timeFrame: 24 months
measure: Complication rate due to radiotherapy (Hepatic artery thrombosis and Portal vein thrombosis)
timeFrame: 24 months
Other outcomes:
Locations:
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
Study officials:
affiliation: Azienda Ospedaliera di Padova
name: Umberto Cillo, MD
role: STUDY_CHAIR
affiliation: Azienda Ospedaliera di Padova
name: Enrico Gringeri, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hemming AW, Reed AI, Fujita S, Foley DP, Howard RJ. Surgical management of hilar cholangiocarcinoma. Ann Surg. 2005 May;241(5):693-9; discussion 699-702. doi: 10.1097/01.sla.0000160701.38945.82.
citation: Rea DJ, Heimbach JK, Rosen CB, Haddock MG, Alberts SR, Kremers WK, Gores GJ, Nagorney DM. Liver transplantation with neoadjuvant chemoradiation is more effective than resection for hilar cholangiocarcinoma. Ann Surg. 2005 Sep;242(3):451-8; discussion 458-61. doi: 10.1097/01.sla.0000179678.13285.fa.
citation: Rosen CB, Heimbach JK, Gores GJ. Liver transplantation for cholangiocarcinoma. Transpl Int. 2010 Jul;23(7):692-7. doi: 10.1111/j.1432-2277.2010.01108.x. Epub 2010 May 20.
citation: Hamilton JP. Epigenetic mechanisms involved in the pathogenesis of hepatobiliary malignancies. Epigenomics. 2010 Apr 1;2(2):233-243. doi: 10.2217/epi.10.9.