Liver Transplantation for Cholangiocarcinoma

July 23, 2013 updated by: University of Utah

Today, available therapies for hilar cholangiocarcinomas (CCA) are not satisfactory. Although these tumors are rare, their study is important because of the high death rates in afflicted patients, rivaling that of pancreatic cancer. Surgical resection offers the only current hope for long-term survival, averaging only 20% in major series1. The reality is such that for the majority of patients, CCA is a diagnosis of despair.

Although surgery has offered the only hope of cure, one of the major limiting factors in achieving long-term survival following surgical resection of CCA is the technical ability to achieve negative resection margins. The presence of malignant cells at the surgical margins following resection is a major prognostic factor predicting recurrence and death. Theoretically, the likelihood of achieving negative margins can be increased with total hepatectomy and orthotopic liver transplantation (OLT). Previous experience with OLT performed in isolation for hilar CCA's has been discouraging with dismal survival rates. However, a recent report has demonstrated that long-term survival can occur in carefully selected patients by combining the benefits of radiotherapy, chemosensitization, and OLT. With this strategy, patients survival rates of 92%, 82%, and 82% at 1, 3, and 5 years after transplantation have been achieved. It is not clear that these preliminary results can be confirmed at other centers, nor is it clear what selection criteria should optimally be used for this treatment strategy.

Our hypothesis is that select patients undergoing liver transplantation for CCA in the context of multi-modality neoadjuvant therapy exhibit survival equivalent to other established indications for liver transplantation as previously demonstrated. We will also attempt to extend previously published criteria for liver transplantation in the setting of CCA by offering this protocol to patients with evidence of intrahepatic disease and regional nodal disease. Patients undergoing transplantation for CCA will be followed longitudinally for their entire post-transplant course and compared with a matched cohort of liver transplant recipients in regard to post-transplant survival, survival on the waiting list, as well as complications pre-and post-transplantation. Explanted livers will be examined for the presence of residual tumor.

Data will be collected on the rate of regional lymph node metastasis, invasion of adjacent organs and tissues, and the rate of peritoneal metastases. The rate of tumor recurrence, site, and time to recurrence will also be assessed.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Objectives Specific Aim #1: Determine whether results obtained in select patients with American Joint Commission on Cancer (AJCC) Staging System Stage I or II CCA are transferable to select patients with T3 or N1 disease.

Specific Aim #2: To determine whether success achieved with the only published protocol currently in use is directly transferable to the University of Utah's liver transplant program.

Liver Transplant Protocol:

The surgical protocol will initially be offered to liver transplant candidates with de novo hilar CCA or CCA arising in the setting of PSC. Diagnosis of CCA will be established by intraluminal brush cytology, intraluminal biopsy, or a carcinoma antigen (CA) 19.9 level greater than 100 ng / mL in the setting of a radiographic malignant stricture. Biliary aneuploidy demonstrated with DIA and FISH will be considered equivalent to cytology.

All patients with CCA will be evaluated by the liver transplant team which includes experienced hepatobiliary and liver transplant surgeons. Patients will be presented at the weekly liver transplant selection conference to assess their candidacy as well as the weekly GI Multidisciplinary Tumor Conference at the Huntsman Cancer Institute. Clinical staging prior to neoadjuvant therapy will include chest and abdominal computed tomography, liver ultrasound, and bone scan. Patients will also undergo endoscopic ultrasound with fine needle aspiration of suspicious lymph nodes. Exclusion criteria will include previous chemotherapy or radiotherapy, uncontrolled infection, a previous malignance other than non-melanoma skin cancer or in situ cervical cancer within the last five years, medical conditions precluding transplantation, metastatic disease (including N2 disease), and patients with hilar tumors extending below the cystic duct.

All patients will undergo staging laparoscopy to rule out the presence of peritoneal disease followed by staging laparotomy. Patients with extrahepatic metastases, local spread of disease to adjacent organs, and N2 nodal disease (metastasis to peripancreatic, periduodenal, periportal, celiac, superior mesenteric, and / or posterior pancreaticoduodenal nodes) will be excluded as will patients with extension of tumor into the main portal vein. Patients with N1 disease (metastasis to lymph nodes within hepatoduodenal ligament) will remain eligible for the protocol. Tumor size will not be included in the exclusion criteria. Patients with evidence of disease progression beyond study criteria will not be eligible to continue on to liver transplantation.

Study Type

Interventional

Enrollment (Actual)

5

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • University of Utah/Huntsman Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

The surgical protocol will initially be offered to liver transplant candidates with de novo hilar CCA or CCA arising in the setting of PSC. Diagnosis of CCA will be established by intraluminal brush cytology, intraluminal biopsy, or a carcinoma antigen (CA) 19.9 level greater than 100 ng / mL in the setting of a radiographic malignant stricture.

Biliary aneuploidy demonstrated with DIA and FISH will be considered equivalent to cytology.

All patients with CCA will be evaluated by the liver transplant team which includes experienced hepatobiliary and liver transplant surgeons. Patients will be presented at the weekly liver transplant selection conference to assess their candidacy as well as the weekly GI Multidisciplinary Tumor Conference at the Huntsman Cancer Institute. Clinical staging prior to neoadjuvant therapy will include chest and abdominal computed tomography, liver ultrasound, and bone scan. Patients will also undergo endoscopic ultrasound with fine needle aspiration of suspicious lymph nodes.

All patients will undergo staging laparoscopy to rule out the presence of peritoneal disease followed by staging laparotomy.

Patients with N1 disease (metastasis to lymph nodes within hepatoduodenal ligament) will remain eligible for the protocol.

Tumor size will not be included in the exclusion criteria. Patients with evidence of disease progression beyond study criteria will not be eligible to continue on to liver transplantation.

** Patients with metastatic disease are not eligible for this trial **

Exclusion criteria will include:

  • previous chemotherapy or radiotherapy,
  • uncontrolled infection,
  • a previous malignance other than non-melanoma skin cancer or in situ cervical cancer within the last five years,
  • medical conditions precluding transplantation,
  • metastatic disease (including N2 disease), and
  • patients with hilar tumors extending below the cystic duct.

Patients with extrahepatic metastases, local spread of disease to adjacent organs, and N2 nodal disease (metastasis to peripancreatic, periduodenal, periportal, celiac, superior mesenteric, and / or posterior pancreaticoduodenal nodes) will be excluded as will patients with extension of tumor into the main portal vein.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: All participants
Procedure: Liver Transplantation
Transplantation will initially be performed with deceased donor livers using the technique of caval-sparing hepatectomy unless suspected caudate involvement or caudate atrophy is a concern regarding the resection margin. Patients will be assigned a provisional Model for End-Stage Liver Disease (MELD) score by the United Network for Organ Sharing (UNOS) Regional Review Board that will make a recipient eligible for transplantation within three months at the time of listing (typically 20-24). A segment of donor iliac artery will be used as an interposition graft to the recipient infrarenal aorta. The hilus will be avoided during dissection and the bile duct, hepatic artery, and portal vein will be divided as low as possible. A frozen section of the bile duct margin will be performed and patient will undergo pancreaticoduodenectomy if positive.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Transplant-related Mortality
Time Frame: 2 years
Determined mortality-related transplant outcomes.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Utah

Investigators

  • Principal Investigator: Jason Schwartz, MD, University of Utah

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2007

Primary Completion (Actual)

July 1, 2011

Study Completion (Actual)

July 1, 2011

Study Registration Dates

First Submitted

June 27, 2008

First Submitted That Met QC Criteria

June 27, 2008

First Posted (Estimate)

July 2, 2008

Study Record Updates

Last Update Posted (Estimate)

July 30, 2013

Last Update Submitted That Met QC Criteria

July 23, 2013

Last Verified

July 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HCI18450

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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