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

NCT01549795 | Unknown DMC

• 1 other identifier: 2372P
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

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.

Conditions

Hilar Cholangiocarcinoma; Primary Sclerosing Cholangitis

Keywords

Liver transplantation; Neoadjuvant radio- chemo-therapy

Outcome Measures

Primary Outcomes (2)

• Percentage of patients free of disease at 24 months post-transplant

  24 months

• Time to recurrence after liver transplant

  24 months

Secondary Outcomes (3)

• 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

Interventions

Liver transplantation PROCEDURE

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

45 Gy external radiations RADIATION

45 Gy in 30 fractions, 1,5 Gy twice a day) and 5-FU iv infusion- 3 week treatment

Endoluminal bile duct Brachytherapy RADIATION

Brachytherapy (20 Gy a 1 cm in 20-25h) - administered 2 weeks after radiotherapy completion

Capecitabine DRUG

Capecitabine - administered till liver transplantation

Pre liver transplantation laparoscopic hand assisted staging PROCEDURE

Pre liver transplantation laparoscopic hand assisted staging for sampling hepatic artery lymph nodes and assessing peritoneal disease.

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Azienda Ospedaliera di Padova: lead

Study Sites (1)

Azienda Ospedaliera di Padova

Padua, Padova, 35100, Italy

RECRUITING

Related Publications (4)

• 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.

  PMID: 15849505 BACKGROUND

• 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.

  PMID: 16135931 BACKGROUND

• 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.

  PMID: 20497401 BACKGROUND

• 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.

  PMID: 20556199 BACKGROUND

Related Links

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

MeSH Terms

Conditions

Klatskin Tumor; Cholangitis, Sclerosing

Interventions

Liver Transplantation; Capecitabine

Condition Hierarchy (Ancestors)

Cholangiocarcinoma; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Cholangitis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Tissue Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Digestive System Surgical Procedures; Surgical Procedures, Operative; Organ Transplantation; Transplantation; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Umberto Cillo, MD

  Azienda Ospedaliera di Padova

  STUDY CHAIR

• Enrico Gringeri, MD

  Azienda Ospedaliera di Padova

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Umberto Cillo, MD

CONTACT

+390498218547; cillo@unipd.it

Enrico Gringeri, MD

CONTACT

+390498218547; enrico.gringeri@unipd.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Hepatobiliary Surgery and Liver Transplantation Unit

Study Record Dates

• First Submitted: March 7, 2012
• First Posted: March 9, 2012
• Study Start: January 1, 2012
• Primary Completion: July 1, 2013
• Last Updated: July 18, 2012

Record last verified: 2012-07

Locations

IT (1)