Safety and Efficacy of Photodynamic Therapy for Bile Duct Invasion of Hepatocellular Carcinoma

Sponsor

Samsung Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT01506115

Collaborator

(none)

Enrollment

Location

Arm

17.9

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The prognosis of patients with obstructive jaundice caused by hepatocellular carcinoma (HCC) is dismal even after biliary drainage; due to malfunction of the biliary drainage tube caused by hemobilia and/or tumor emboli. Photodynamic therapy (PDT) in hilar cholangiocarcinoma improves biliary drainage and prolongs survival. The aims of this study were to assess the safety and efficacy of PDT in unresectable HCC with bile duct invasion.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma Obstructive Jaundice	Drug: Photofrin	N/A

Detailed Description

As more therapies are available for patients with hepatocellular carcinoma (HCC), the survival rate has improved. The incidence of jaundice in patients with HCC is reported as 5-44%, and substantial number of patients experience obstructive jaundice. With the improvement of survival in patients with HCC, it is not uncommon to encounter HCC patients with obstructive jaundice in clinical practice.

The prognosis of patients with obstructive jaundice caused by HCC is dismal due to progressive liver failure, rapid tumor progression and ineffective biliary drainage. The mean survival of HCC with obstructive jaundice after biliary drainage ranges from 2.5 to 4.5 months. Effective biliary drainage to improve jaundice and liver function is inevitably needed for further treatment. However, it is difficult to maintain the patency of the bile duct because recurrent obstruction frequently develops due to hemobilia.

Photodynamic therapy (PDT) with biliary drainage is a promising treatment option for advanced cholangiocarcinoma. Presence of the photosensitizer only itself is nontoxic, but showing light with specific wavelengths can induce cytotoxicity. The systemically administrated photosensitizer accumulates preferentially in proliferating tissue. If this targeted lesion is then illuminated by light of a specific wavelength, the activated photosensitizer generates reactive oxygen species, which trigger cell death by apoptosis and necrosis of the cells in the specific area. Experience with PDT in cholangiocarcinoma suggests that a survival benefit can be achieved by prolonged relief of the obstruction.

The investigators hypothesized that conducting PDT with biliary stenting in patients with obstructive jaundice caused by bile duct invasion of HCC would improves stent patency and other clinical outcomes. The aim of this study was to evaluate the safety and efficacy of PDT in HCC patients with bile duct invasion.

Study Design

Study Type:

Interventional

Actual Enrollment :

11 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Observational Study for Safety and Efficacy of Photodynamic Therapy for Bile Duct Invasion of Hepatocellular Carcinoma

Study Start Date :

Sep 1, 2009

Actual Primary Completion Date :

Mar 1, 2011

Actual Study Completion Date :

Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HCC with bile duct invasion Photodynamic therapy with biliary drainage in patients with bile duct invasion of unresectable HCC	Drug: Photofrin Photodynamic therapy: Intravenous Photofrin at a dose of 2 mg/kg body weight, 48 hours before photoactivation by intraluminal light illumination Other Names: Photofrin (Axcan Pharma Inc., Mount-Saint-Hilaire, Canada)

Arm

Intervention/Treatment

Experimental: HCC with bile duct invasion

Photodynamic therapy with biliary drainage in patients with bile duct invasion of unresectable HCC

Drug: Photofrin

Photodynamic therapy: Intravenous Photofrin at a dose of 2 mg/kg body weight, 48 hours before photoactivation by intraluminal light illumination

Other Names:

Photofrin (Axcan Pharma Inc., Mount-Saint-Hilaire, Canada)

Outcome Measures

Primary Outcome Measures

Complications associated with the procedure [Six months]
Procedure related cholangitis: fever accompanied by biliary pain that developed within three days after PDT without other infection Procedure related pancreatitis: abdominal pain and increases in amylase and lipase levels threefold higher than normal Procedure related bleeding: more than a 5% decrease in hematocrit compared to the initial value and coexisting bleeding on abdominal CT or endoscopy Complications associated with the photosensitizer: classified as photosensitivity, burn, and pigmentation

Secondary Outcome Measures

Improvement of jaundice [Six months]
The improvement of jaundice was defined as a decrease in total bilirubin by more than 30% of the pre-procedural value.
Disappearance of hemobilia [Six months]
Disappearance of hemobilia was defined when there was no more evidence of bleeding in patients with previous hemobilia after PDT.
Survival time [Six months]
Survival time was defined as the duration from the date of imaging showing bile duct invasion of HCC to the date of death or to the last follow-up.

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Known HCC: Diagnosis of HCC based on the 2005 AASLD (American Association for the Study of Liver Diseases) practice guidelines
Unresectable HCC: Determined based on the BCLC (Barcelona-Clinic-Liver-Cancer) staging and treatment system
Bile duct invasion of HCC: Confirmed by pathology via endoscopic retrograde cholangiopancreatogram (ERCP) or percutaneous transhepatic biliary drainage (PTBD). In case pathological diagnosis is clinically impossible, confirmed by dynamic CT or MRI showing that typical arterial enhancing mass in dilated bile duct and previous HCC diagnosis.