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

Hepatocellular Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01506115
• Other study ID #: 2009-09-048
• Status: Completed
• Phase: N/A
• First received: December 29, 2011
• Last updated: November 17, 2015
• Start date: September 2009
• Est. completion date: March 2011

Study information

• Verified date: January 2012
• Source: Samsung Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Korea: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: March 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years to 70 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma
• Jaundice
• Jaundice, Obstructive
• Obstructive Jaundice

Intervention

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

Locations

Country	Name	City	State
Korea, Republic of	Samsung Medical Center 81 Irwon-Ro Gangnamgu	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Samsung Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (23)

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Cho HC, Lee JK, Lee KH, Lee KT, Paik S, Choo SW, Do YS, Choo IW. Are endoscopic or percutaneous biliary drainage effective for obstructive jaundice caused by hepatocellular carcinoma? Eur J Gastroenterol Hepatol. 2011 Mar;23(3):224-31. doi: 10.1097/MEG.0b013e3283436ff6. — View Citation

Dumoulin FL, Gerhardt T, Fuchs S, Scheurlen C, Neubrand M, Layer G, Sauerbruch T. Phase II study of photodynamic therapy and metal stent as palliative treatment for nonresectable hilar cholangiocarcinoma. Gastrointest Endosc. 2003 Jun;57(7):860-7. — View Citation

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Matsueda K, Yamamoto H, Umeoka F, Ueki T, Matsumura T, Tezen T, Doi I. Effectiveness of endoscopic biliary drainage for unresectable hepatocellular carcinoma associated with obstructive jaundice. J Gastroenterol. 2001 Mar;36(3):173-80. — View Citation

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Ortner ME, Caca K, Berr F, Liebetruth J, Mansmann U, Huster D, Voderholzer W, Schachschal G, Mössner J, Lochs H. Successful photodynamic therapy for nonresectable cholangiocarcinoma: a randomized prospective study. Gastroenterology. 2003 Nov;125(5):1355-63. — View Citation

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Shim CS, Cheon YK, Cha SW, Bhandari S, Moon JH, Cho YD, Kim YS, Lee LS, Lee MS, Kim BS. Prospective study of the effectiveness of percutaneous transhepatic photodynamic therapy for advanced bile duct cancer and the role of intraductal ultrasonography in response assessment. Endoscopy. 2005 May;37(5):425-33. — View Citation

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* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complications associated with the procedure	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	Six months	Yes
Secondary	Improvement of jaundice	The improvement of jaundice was defined as a decrease in total bilirubin by more than 30% of the pre-procedural value.	Six months	No
Secondary	Disappearance of hemobilia	Disappearance of hemobilia was defined when there was no more evidence of bleeding in patients with previous hemobilia after PDT.	Six months	No
Secondary	Survival time	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.	Six months	No