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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2012 by Azienda Ospedaliera di Padova.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Prof. Umberto Cillo, Azienda Ospedaliera di Padova
ClinicalTrials.gov Identifier:
NCT01549795
First received: March 7, 2012
Last updated: July 17, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention
Hilar Cholangiocarcinoma
Primary Sclerosing Cholangitis
Procedure: Liver transplantation
Radiation: 45 Gy external radiations
Radiation: Endoluminal bile duct Brachytherapy
Drug: Capecitabine
Procedure: Pre liver transplantation laparoscopic hand assisted staging

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Trapianto di Fegato Per Colangiocarcinoma (CCA) Ilare in Associazione a Radio e Chemioterapia Neoadiuvante

Resource links provided by NLM:


Further study details as provided by Azienda Ospedaliera di Padova:

Primary Outcome Measures:
  • Percentage of patients free of disease at 24 months post-transplant [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Time to recurrence after liver transplant [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression disease free survival [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Overall 2 years survival after liver transplantation [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Complication rate due to radiotherapy (Hepatic artery thrombosis and Portal vein thrombosis) [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 33
Study Start Date: January 2012
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    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.
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01549795

Contacts
Contact: Umberto Cillo, MD +390498218547 cillo@unipd.it
Contact: Enrico Gringeri, MD +390498218547 enrico.gringeri@unipd.it

Locations
Italy
Azienda Ospedaliera di Padova Recruiting
Padova, Italy, 35100
Contact: Umberto Cillo, MD    +390498218547    cillo@unipd.it   
Contact: Enrico Gringeri, MD    +390498218547    enrico.gringeri@unipd.it   
Principal Investigator: Umberto Cillo, MD         
Sub-Investigator: Enrico Gringeri, MD         
Sub-Investigator: Domenico Bassi, MD         
Sub-Investigator: Giacomo Zanus, MD         
Sub-Investigator: Daniele Neri, MD         
Sub-Investigator: Francesco D'Amico, MD         
Sub-Investigator: Alessandro Vitale, MD         
Sponsors and Collaborators
Azienda Ospedaliera di Padova
Investigators
Study Chair: Umberto Cillo, MD Azienda Ospedaliera di Padova
Principal Investigator: Enrico Gringeri, MD Azienda Ospedaliera di Padova
  More Information

Additional Information:
Publications:
Responsible Party: Prof. Umberto Cillo, Director of the Hepatobiliary Surgery and Liver Transplantation Unit, Azienda Ospedaliera di Padova
ClinicalTrials.gov Identifier: NCT01549795     History of Changes
Other Study ID Numbers: 2372P
Study First Received: March 7, 2012
Last Updated: July 17, 2012
Health Authority: Italy: Ethics Committee

Keywords provided by Azienda Ospedaliera di Padova:
Liver transplantation
Neoadjuvant radio- chemo-therapy

Additional relevant MeSH terms:
Cholangitis
Cholangitis, Sclerosing
Cholangiocarcinoma
Klatskin's Tumor
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Capecitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 22, 2014