Safety and Tumoricidal Effect of Low Dose Foscan PDT in Patients With Inoperable Bile Duct Cancers (PDT)

Safety and Tumoricidal Effect of Low Dose Temoporfin Photodynamic Therapy in Patients With Inoperable Bile Duct Cancers (Foscan® Study)

In this study, we hope to evaluate the safety of PDT using temoporfin plus endoscopic stents in patients with inoperable bile duct cancers. In addition as a preliminary study we sought to determine if the treatment can reduce tumor volume in the short term.

Study Overview

• Status: Completed
• Conditions: Cholangiocarcinoma; Klatskin Tumor; Tumor
• Intervention / Treatment: Drug: Temoporfin

Detailed Description

Cholangiocarcinoma is a tumor associated with a grave prognosis. The only curative treatment is surgery or liver transplantation. Only about 10-20% of patients with the tumor are operated upon. In the majority of patients, the tumor is often diagnosed at a late stage. Many patients are not operated upon owing to their advanced age or comorbid illnesses. These patients suffer from intense pruritus a result of obstructive jaundice, recurrent biliary sepsis and progressive hepatic failure leading to death. Quality in life in these patients is poor. The median survival in these patients is around 6 months. The palliative treatment is stents inserted either at ERCP or through a percutaneous transhepatic route. Many return with recurrent cholangitis necessitating frequent stent changes. Photodynamic therapy (PDT) in combination with stenting is the only proven treatment that confers a survival benefit when compared to stenting alone. Two randomized controlled trials have shown significant survival advantage in patients treated by PDT in addition to stenting compared to stenting alone. Ortner et al. 1 randomized 39 patients with inoperable cholangiocarinoma to endoscopic stents with or without PDT. Median survival in those given PDT was 493 days compared to that of 98 days in those with stents alone. Survival difference was again wide in favor of PDT use in another randomized controlled study by Zoepf et al 2 (median survival 630 vs. 210 days). In addition, PDT improves quality of life and cholestasis in patients with cholangiocarcinoma. In a series from Germany, survival after PDT and stenting compared favorably to R1 and R2 resections. 3 Despite of the evidence, PDT for inoperable cholangiocarcinoma is not available in Hong Kong.

Meso-tetrahydroxyphenylchlorin (mTHPC, Foscan®) is a photosensitizer for PDT in cholangiocarcinoma. In compared with other agents such as Photofin and Photosan, PDT treatment using temoporfin at a low dose (3 mg per treatment) is associated with a deeper tissue penetration (4-6mm) and a reduced period of photosensitivity.

In this study, we hope to evaluate the safety of PDT using temoporfin plus endoscopic stents in patients with inoperable bile duct cancers. In addition as a preliminary study we sought to determine if the treatment can reduce tumor volume in the short term.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: James YW LAU, MD; Phone Number: +85226321411; Email: laujyw@surgery.cuhk.edu.hk
• Study Contact Backup: Name: Kim WL AU, MSc; Phone Number: +85226322640; Email: kimau@surgery.cuhk.edu.hk

Study Locations

• Hong Kong
  • N.t.
    • Shatin, N.t., Hong Kong
      • Endoscopy Centre, Prince of Wales Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with inoperable cholangiocarcinoma belonging to all Bismuth Corlette classification.
• Karnofsky index >30%
• Satisfactory relief of jaundice (serum bilirubin < 100µmol/L) with biliary prostheses inserted either at ERCP or via percutaneous transhepatic routes.
• Absence of biliary sepsis
• Age 18-80
• Provision of written consent
• No evidence of metastatic disease

Exclusion Criteria:

• Porphyria
• Previous inserted metallic biliary stents
• Refusal to provide a written consent.
• Moribund from disseminated disease or comorbidities
• Pregnant or lactating women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Foscan; A single treatment with Temoporfin (Foscan) 3 mg given intravenously followed by PDT with laser light at 652 nm (Ceralas, Biolitec, Germany) within 72 hours	Drug: Temoporfin; A single treatment with Temoporfin (Foscan) 3 mg given intravenously followed by PDT with laser light at 652 nm (Ceralas, Biolitec, Germany) within 72 hours; Other Names: Foscan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety (will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0)	Safety (will be graded according to the Common Terminology Criteria for Adverse Events	10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor response as categorized by the World Health Organization criteria at 8 weeks as assessed by ERCP and Intraduct ultrasound	Tumor response as categorized by the World Health Organization criteria at 8	10 years
Relief of jaundice at 8 weeks (<50% pretreatment serum bilirubin)	Relief of jaundice at 8 weeks (<50% pretreatment serum bilirubin)	10 years
Cholangitis and stent occlusions requiring stent change (will be assessed based on blood tests and ERCP findings)	Cholangitis and stent occlusions requiring stent change (will be assessed based on blood tests and ERCP findings)	10 years
Quality of life (in every visit, European Organization for Research and Treatment of Cancer core questionnaire [EORTC QLQ-C30] will be filled and specific symptom enquiry is made; itchiness, fever and general well-being over a Likert 0-4 scale.	Quality of life (in every visit, European Organization for Research and Treatment of Cancer core questionnaire [EORTC QLQ-C30] will be filled and specific symptom enquiry is made; itchiness, fever and general well-being over a Likert 0-4 scale.	10 years

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Investigators: Principal Investigator: James YW LAU, MD, CUHK

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2014
• Primary Completion (Actual): April 12, 2023
• Study Completion (Actual): August 12, 2023

Study Registration Dates

• First Submitted: February 24, 2016
• First Submitted That Met QC Criteria: December 21, 2016
• First Posted (Estimated): December 26, 2016

Study Record Updates

• Last Update Posted (Actual): August 22, 2023
• Last Update Submitted That Met QC Criteria: August 20, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Photodynamic therapy; Endoscopic retrograde cholangiopancreatography; Inoperable cholangiocarcinoma
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Biliary Tract Diseases; Bile Duct Diseases; Biliary Tract Neoplasms; Cholangiocarcinoma; Klatskin Tumor; Bile Duct Neoplasms; Antineoplastic Agents; Photosensitizing Agents; Dermatologic Agents; Temoporfin
• Other Study ID Numbers: Foscan

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO