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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Samsung Medical Center
ClinicalTrials.gov Identifier:
NCT01506115
First received: December 29, 2011
Last updated: January 18, 2012
Last verified: January 2012
  Purpose

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 Intervention
Hepatocellular Carcinoma
Obstructive Jaundice
Drug: Photofrin

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Observational Study for Safety and Efficacy of Photodynamic Therapy for Bile Duct Invasion of Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by Samsung Medical Center:

Primary Outcome Measures:
  • Complications associated with the procedure [ Time Frame: Six months ] [ Designated as safety issue: Yes ]
    • 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 [ Time Frame: Six months ] [ Designated as safety issue: No ]
    The improvement of jaundice was defined as a decrease in total bilirubin by more than 30% of the pre-procedural value.

  • Disappearance of hemobilia [ Time Frame: Six months ] [ Designated as safety issue: No ]
    Disappearance of hemobilia was defined when there was no more evidence of bleeding in patients with previous hemobilia after PDT.

  • Survival time [ Time Frame: Six months ] [ Designated as safety issue: No ]
    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.


Enrollment: 11
Study Start Date: September 2009
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

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.

  Eligibility

Ages Eligible for Study:   19 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01506115

Locations
Korea, Republic of
Samsung Medical Center
Seoul, 50, Irwon-Dong, Gangnam-Gu, Korea, Republic of, 135-710
Sponsors and Collaborators
Samsung Medical Center
Investigators
Study Director: Kwang Hyuck Lee, M.D. Samsung Medical Center
  More Information

Publications:

Responsible Party: Samsung Medical Center
ClinicalTrials.gov Identifier: NCT01506115     History of Changes
Other Study ID Numbers: 2009-09-048
Study First Received: December 29, 2011
Last Updated: January 18, 2012
Health Authority: South Korea: Institutional Review Board

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

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Jaundice
Carcinoma
Jaundice, Obstructive
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Hyperbilirubinemia
Pathologic Processes
Skin Manifestations
Signs and Symptoms
Hematoporphyrin Derivative
Dihematoporphyrin Ether
Trioxsalen
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Photosensitizing Agents
Dermatologic Agents
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on September 16, 2014