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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01506115
Recruitment Status : Completed
First Posted : January 9, 2012
Last Update Posted : November 20, 2015
Information provided by (Responsible Party):
Samsung Medical Center

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 Not Applicable

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
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 : September 2009
Actual Primary Completion Date : March 2011
Actual Study Completion Date : March 2011

Resource links provided by the National Library of Medicine

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

Primary Outcome Measures :
  1. Complications associated with the procedure [ Time Frame: 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 :
  1. Improvement of jaundice [ Time Frame: Six months ]
    The improvement of jaundice was defined as a decrease in total bilirubin by more than 30% of the pre-procedural value.

  2. Disappearance of hemobilia [ Time Frame: Six months ]
    Disappearance of hemobilia was defined when there was no more evidence of bleeding in patients with previous hemobilia after PDT.

  3. Survival time [ Time Frame: 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.

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Ages Eligible for Study:   19 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Exclusion Criteria:

  • Severe renal disease
  • Severe cardiac disease
  • Bleeding tendency
  • Porphyria

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01506115

Korea, Republic of
Samsung Medical Center 81 Irwon-Ro Gangnamgu
Seoul, Korea, Republic of, 06351
Sponsors and Collaborators
Samsung Medical Center
Study Director: Kwang Hyuck Lee, M.D. Samsung Medical Center


Responsible Party: Samsung Medical Center Identifier: NCT01506115     History of Changes
Other Study ID Numbers: 2009-09-048
First Posted: January 9, 2012    Key Record Dates
Last Update Posted: November 20, 2015
Last Verified: January 2012

Keywords provided by Samsung Medical Center:
Hepatocellular carcinoma
Obstructive jaundice
Photodynamic therapy

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Jaundice, Obstructive
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Pathologic Processes
Skin Manifestations
Signs and Symptoms
Dihematoporphyrin Ether
Hematoporphyrin Derivative
Antineoplastic Agents
Dermatologic Agents
Photosensitizing Agents