Photodynamic Therapy (PDT) for Palliation of Cholangiocarcinoma

Study Overview
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Brief Summary
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Successful palliation of biliary obstruction is the main goal for reducing morbidity and mortality in patients with biliary disease and biliary obstruction related to cholangiocarcinoma. Surgical intervention for the sale is unfortunately complicated by a 30-day postoperative mortality rate of between 7 and 24%. Moreover, because of recovery time the quality of life following surgery is only improved in a minority. At present endoscopic insertion of a plastic or metal stent is the method of choice to relieve obstructive jaundice without the high morbidity and mortality associated with surgery. But this relief is unfortunately temporary since stents tend to become obstructed and the fact that effective biliary drainage in the proximal lesion is challenging. Photodynamic Therapy (PDT) is a new therapeutic approach that specifically targets neoplastic cells. This therapy involves the intravenous administration of a photosensitizing agent followed by activation of the agent by illumination with non-thermal light of a specific wavelength, resulting in cell death from direct cytotoxicity and ischemic necrosis. A randomized controlled trial study by Ortner et all confirmed the significant advantage of PDT with regard to relief of jaundice, quality of life, and survival. In photodynamic therapy (PDT) the uniform distribution of externally applied light is desirable but often difficult to achieve. An optical fiber tip producing cylindrical or lateral light emission can facilitate the application of laser energy by direct implantation of the tip into solid tumors. However, currently used FDA approved glass diffusers used in standard of care PDT might break in the bile ducts causing injury since they are not meant to be used within bile ducts through an endoscope or choledochoscope. Hence, there is a need to evaluate and introduce more efficient and safe non-glass cylindrical optic fiber diffuser for photo dynamic therapy in the bile ducts. Recent studies have shown that the Pioneer plastic optic diffuser is safe and effective in photodynamic therapy, it can be also used via a choledochoscope. We aim to add to the clinical evidence by conducting an open label observational study trial using this fiber optic diffuser during photo dynamic therapy in the bile ducts.

Detailed Description
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Cholangiocarcinoma (CCA) is the second most common malignancy arising within the liver, and the association of this malignant condition with high morbidity and mortality is well recognized. It originates from the epithelium of bile ducts or ductules. Two types have been described: the peripheral type occurring in the parenchyma of the liver and the central type occurring within or related to the major bile ducts. Surgery can offer a curative chance, but only a minority of patients are candidates for this therapy at initial presentation since most patients are found with an unresectable tumor. In unresectable cases, the median survival is 6 months. Since morbidity and mortality from CCA occurs because of biliary obstruction, successful palliation of that complication is the main goal in these patients. Surgical biliary bypass can be offered in order to prolong life and relieve symptoms. This intervention is unfortunately complicated by 30-day postoperative mortality rate between 7 and 24%. Moreover, the quality of life following surgery is only improved in a minority because of the time needed to recover from surgery. Endoscopic biliary stenting during endoscopic retrograde cholangiopancreatography (ERCP) offers relief from obstructive jaundice without the high morbidity and mortality associated with surgery. In addition, a study by Luman et al even showed significant improvement in emotional, cognitive and global health scores following stenting. But this relief is unfortunately temporary since stents tend to become obstructed. Local therapies including iridium brachytherapy and photodynamic therapy (PDT) may prevent or postpone these problems. For more information about PDT, please see the 'Citations' section.

Official Title
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Open-label Observational Study of Plastic Cylindrical Fiber Optic Diffuser (Pioneer Optics) in Photodynamic Therapy for the Management of Cholangiocarcinoma.

Conditions
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Cholangiocarcinoma, Biliary Stricture, Biliary Obstruction, Bile Duct Cancer

Intervention / Treatment
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* Procedure: Photodynamic Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with cholangiocarcinoma Patient is age 18 years or older Patient is receiving Photodynamic therapy with stent(s) placement as part of their original treatment plan Patients must have adequate coagulation as defined below: Patient's INR ≤ 2 within 30 days of treatment Patient's platelets > 50,000/cmm within 30 days of treatment Exclusion Criteria: Subject has acute porphyria. Subjects exhibiting neurologic or cutaneous symptoms will undergo urinary delta-aminolevulinic acid and porphobilinogen dosage tests to determine severity. Subject is pregnant. Subject is allergic to Photofrin. Subject has uncorrected coagulopathy Subject is unstable for ERCP

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PDT Group<br>Subjects who receive Photodynamic therapy with plastic optic diffuser. | Procedure: Photodynamic Therapy<br>* Photofrin and Photodynamic therapy using the plastic optic diffuser, conducted during Standard of care Endoscopic retrograde cholangiopancreatography (ERCP)<br>* Other names: Laser;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy Profile | To assess the efficacy of a plastic cylindrical fiber optic diffuser (Pioneer Optics) in photodynamic therapy for the management of Cholangiocarcinoma by visualization of visible necrosis of target tissue in bile ducts after the application of the device. | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Profile | To assess the the number and intensity of adverse events occurring due to the application of the research device. | 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cholangiocarcinoma, Biliary Stricture, Biliary obstruction, Bile Duct Cancer, PDT, Photodynamic Therapy, Plastic optic Diffuser, Laser