Liver Transplantation for Cholangiocarcinoma

Cancer Clinical Trial

Official title:

Liver Transplantation for Cholangiocarcinoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00708877
• Other study ID #: HCI18450
• Status: Terminated
• Phase: N/A
• First received: June 27, 2008
• Last updated: July 23, 2013
• Start date: March 2007
• Est. completion date: July 2011

Study information

• Verified date: July 2013
• Source: University of Utah
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Cancer
• Cholangiocarcinoma
• Liver

Intervention

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.

Locations

Country	Name	City	State
United States	University of Utah/Huntsman Cancer Institute	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
University of Utah

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Transplant-related Mortality	Determined mortality-related transplant outcomes.	2 years	No