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

Primary Sclerosing Cholangitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01549795
• Other study ID #: 2372P
• Status: Recruiting
• Phase: N/A
• First received: March 7, 2012
• Last updated: July 17, 2012
• Start date: January 2012

Study information

• Verified date: July 2012
• Source: Azienda Ospedaliera di Padova
• Contact: Umberto Cillo, MD
• Phone: +390498218547
• Email: cillo[@]unipd.it
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 33
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cholangiocarcinoma
• Cholangitis
• Cholangitis, Sclerosing
• Hilar Cholangiocarcinoma
• Klatskin's Tumor
• Primary Sclerosing Cholangitis

Intervention

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
• 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.

Locations

Country	Name	City	State
Italy	Azienda Ospedaliera di Padova	Padova

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Ospedaliera di Padova

Country where clinical trial is conducted

Italy, 

References & Publications (4)

Hamilton JP. Epigenetic mechanisms involved in the pathogenesis of hepatobiliary malignancies. Epigenomics. 2010 Apr 1;2(2):233-243. — View 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. — View 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. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients free of disease at 24 months post-transplant		24 months	No
Primary	Time to recurrence after liver transplant		24 months	No
Secondary	Progression disease free survival		24 months	No
Secondary	Overall 2 years survival after liver transplantation		24 months	No
Secondary	Complication rate due to radiotherapy (Hepatic artery thrombosis and Portal vein thrombosis)		24 months	No

External Links

•   Hepatobiliary surgery and Liver Transplantation Unit, University Hospital of Padua (Italy)