Safety Study of Liver Transplantation for Hilar Cholangiocarcinoma

Phase 1 Study of Liver Transplantation Combined With Neoadjuvant Radiochemotherapy for Unresectable Hilar Cholangiocarcinoma

Hilar cholangiocarcinoma is a highly malignant tumor. Surgical resection or simple liver transplantation leads to poor prognosis accompanied by high recurrence rate and low survival rate. The newly proposed neoadjuvant therapy with liver transplantation strategy shows promising clinical application, which once reported 5-year survival rate 82%. However, transplantation centers conducting this kind of research are limited due to its complexity and long-term. The investigators would like to conduct a clinical trial for only unresectable hilar cholangiocarcinoma patients who should take neoadjuvant brachytherapy and chemoradiotherapy followed by orthotopic liver transplantation.

Study Overview

• Status: Unknown
• Conditions: Hilar Cholangiocarcinoma
• Intervention / Treatment: Other: liver transplantation combined with neoadjuvant therapy

Detailed Description

The enrolled patients should be prescribed with several examinations when admitted to hospital consisting of CT, MRI, MRCP, ECT, PET/CT and other laboratory tests. All preoperative examinations must indicate that enrolled individuals should be diagnosed as unresectable hilar cholangiocarcinoma. In addition, repetitive ERCP manipulations are needed in order to obtain positive results by brush cytology. Of course, all enrolled patients should be adherent to the fundamental principles of liver transplantation.

We employed I-125 radioactive plastic stents (patent No: ZL 201610116321.3) to conduct brachytherapy. Each stent composed of a drainage tube with a stab at both ends that had a stabilizing effect. Two opposite channels were made in the wall of stents paralleling the drainage lumen, with irradiation window in the lateral wall of the channel. The diameter of the channel is a bit smaller than that of the radioactive seeds, so as is the length and width of irradiation windows. The stents are so designed to immobilize seeds and radiate properly. The radioactive I-125 seeds were 4.5 mm long and 0.8 mm thick, and their half-life was 60.1 days. The nasobiliary radiography was performed to determine the length of involvement of bile duct.Corresponding radioactive seeds are then put in appropriate location with biliary stents by ERCP procedure.

About a month later, external beam radiotherapy was administrated to a target dose of 30Gy in 30 fractions, 1.5Gy twice per day. Concomitantly, Intravenous capecitabine was given at 1.0g bid for two weeks, which is repeated after 14 days until transplantation.

Immunosuppressive therapy was provided with tacrolimus, mycophenolate and corticosteroids. Corticosteroids were withdrawn a week later. Chemotherapy was continued 1 month after OLT with expected 3 courses.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Recruiting
      • Hepatobiliary department, Nanjing DrumTower Hospital
      • Contact: Yitao Ding, MD; Phone Number: 66866 86 25 83304616; Email: yitao_ding@163.com
      • Contact: Jinyang Gu, MD; Phone Number: 60911 86 25 83304616; Email: gjynyd@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

unresectable hilar cholangiocarcinoma tumor diameter less than 3 cm adherence to liver transplantation requirements

Exclusion Criteria:

intrahepatic cholangiocarcinoma uncontrolled infection intrahepatic or extrahepatic metastasis distant lymph node metastasis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: unresectable hilar cholangiocarcinoma; control group
Experimental: liver transplantation; liver transplantation combined with neoadjuvant radiochemotherapy	Other: liver transplantation combined with neoadjuvant therapy; liver transplantation combined with neoadjuvant radiochemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
survival rate	1-yr survival rate
survival rate	3-yr survival rate
survival rate	5-yr survival rate
tumor-free survival rate	1-yr tumor-free survival rate
tumor-free survival rate	3-yr tumor-free survival rate
tumor-free survival rate	5-yr tumor-free survival rate

Secondary Outcome Measures

Outcome Measure	Time Frame
acute rejection rate	usually within 2 months after liver transplantation
chronic rejection rate	usually 2 months upon liver transplantation

Collaborators and Investigators

• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Investigators: Study Chair: Yitao Ding, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Anticipated): December 1, 2016
• Study Completion (Anticipated): December 1, 2016

Study Registration Dates

• First Submitted: June 14, 2014
• First Submitted That Met QC Criteria: June 26, 2014
• First Posted (Estimate): June 30, 2014

Study Record Updates

• Last Update Posted (Estimate): June 30, 2014
• Last Update Submitted That Met QC Criteria: June 26, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Cholangiocarcinoma; Klatskin Tumor
• Other Study ID Numbers: 20140615