Photodynamic Therapy for Cholangiocarcinoma

Study Overview
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Brief Summary
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Comparison of the bile duct patency with photodynamic therapy (PDT) and regular Endoscopic Retrograde Cholangiopancreatography(ERCP) stents in unresectable cholangiocarcinoma.

Detailed Description
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Cholangiocarcinoma is a malignant tumor originating from the bile duct epithelium, accounting for about 70% of the malignant tumors of the bile duct system. Patients have no obvious clinical symptoms in the early stage. After late diagnosis, the effective treatment is surgical resection and & or liver transplantation, and chemotherapy is only used as adjuvant or palliative treatment. Some types of cholangiocarcinomas, such as hilar cholangiocarcinomas, are difficult to achieve radical resection due to their anatomical location, early invasions and are prone to recurrence with a poor long-term efficacy after surgery. Therefore, the comprehensive treatment of cholangiocarcinoma by multiple means urgently needs to be explored. In recent years, photodynamic therapy (PDT), as a new local treatment method, has attracted increasing attention. This study investigates the bile duct patency and effectiveness of photodynamic therapy compare with ordinary ERCP treatment for cholangiocarcinoma including the median survival, overall survival, and other indicators of side effects.

Official Title
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Evaluation of Bile Duct Patency After Photodynamic Therapy in Unresectable Cholangiocarcinoma：a Prospective Non-randomized Controlled Study

Conditions
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Cholangiocarcinoma Non-resectable

Intervention / Treatment
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* Drug: Hematoporphyrin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ERCP cholangiocarcinoma（the tumor is unresectable or patient can't accept surgery in the situation, the tumor can be resected but the patients cannot tolerate surgery）; Exclusion Criteria: Proximal cholangiocarcinoma (Bismuth type Ⅲ-Ⅳ, or intra-hepatic cholangiocarcinoma); Patients with Karnofsky Performance Scale (KPS) score≤70； Expected survival≤3months； Patients with porphyria； Coagulation dysfunction (INR> 1.5) and low peripheral blood platelet count(<50×10^9 / L) or using anti-coagulation drugs； Bilirubin could not be reduced to less than 100mmol/L within 1 month after drainage； Patients have intrahepatic metastasis or distant metastasis； Patients with no pathological diagnosis； known to allergic to study drug(porphyrin drugs) or other similar and related compounds； Other photosensitizers have been used within 4 weeks prior； Metal biliary stents were placed previously； Patients with contraindications to ERCP； Patients with HIV infection； Pregnant, parturient, or breastfeeding women； Patients complicated with other malignant tumors； Patients with severe liver function damage； Patients who were in cachexia, liver abscess, or advanced patients who were unable to tolerate PDT； Patients with other serious physical or mental illnesses that prevent researchers to enroll them in this study as subjects； Patients with other contraindications for photodynamic therapy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PDT with stent<br>Before photodynamic therapy, candidate patients undergoing biliary biopsy and biliary duct drainage. If pathology shows a bile duct malignancy, PDT therapy will carry out until total bilirubin drops below 100 μmol/L.Patients with negative skin test of hematoporphyrin Injection (3.0-5.0mg/Kg plus saline 250 mL intravenous drip, the drip was completed within 1 hour) and keep patients away from the light. The first PDT therapy was performed 24 hours after infusion of hematoporphyrin injection by ERCP. The biliary tumor necrosis was observed and the biliary tract was cleaned up 24 hours later and then PDT therapy showed again if necessary. Multiple plastic stents or metal stent will be placed. Follow up regularly after the procedure, PDT therapy would be given again in 3 months. | Drug: Hematoporphyrin<br>* Patients with negative skin test of hematoporphyrin Injection (3.0-5.0mg/Kg plus saline 250 mL intravenous drip, the drip was completed within 1 hour) and keep patients away from the light. The first PDT therapy was performed 24 hours after infusion of hematoporphyrin injection by ERCP. The biliary tumor necrosis was observed and the biliary tract was cleaned up 24 hours later and then PDT therapy showed again if necessary. Multiple plastic stents or bald metal stents will be placed. Follow up regularly after the procedure, PDT therapy would be given again in 3 months.<br>* Other names: ERCP stents;|
| No Intervention: ERCP stent<br>After obtaining bile duct biopsy, the candidates were placed with biliary plastic stents or metal stents directly. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bile duct patency | Patency period of the stents after treatment | 3years (every 3 months or obstruction appears) | 
| Median survival time | The time of the half of the patients survived after initial therapy | 3years (every 3 months） | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | The time from initial therapy to death or the end of the study | 5years (every 3 months） | 
| Karnofsky Performance Scale | The Karnofsky Performance Scale scores range from 0 (death) to 100 (normal). The lower the Karnofsky score, the worse likelihood of survival. However, the premature termination of the study does not allow for a meaningful analysis of the scale where 100% means no complaints with no evidence of disease, 80% is a normal activity with effort and some signs or symptoms of the disease. pre-operation, 1 month, 3 months, 6 months, 9 months, and 12 months after the operation | 1year (baseline and every 3 months） | 
| European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 | EORTCQLQ-C30 score used to assess the quality of life of cancer patients. EORTCQLQ-C30 score contains 30 questions, the first 28 questions include 1-4 points, the lower the score, the better; but the latter two questions include 1-7 points, the higher the score, the better. pre-operation, 1 month, 3 months, 6 months, 9 months, and 12 months after the operation | 1year (baseline and every 3 months） | 
| The change of weight in kilograms | Weight changes of the patient before and after PDT treatment, pre-operation, 1 month, 3 months, 6 months, 9 months, and 12 months after the operation | 1year (baseline and every 3 months） | 
| Beck Anxiety Inventory | BAI is a 21-item self-reported questionnaire that measures the existence and severity of symptoms of anxiety. Each of the 21 items on the BAI tool represents an anxiety symptom. A total score of 0 - 7 is interpreted as a Minimal level of anxiety; 8 - 15 as Mild; 16 - 25 as Moderate, and; 26 - 63 as Severe, pre-operation, 1 month, 3 months, 6 months, 9 months and 12 months after the operation | 1year (baseline and every 3 months） | 
| Cumulative treatment costs | The overall treatment costs from initial PDT to death or the end of the study | 5years (baseline and in each year） | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ERCP, PDT, Cholangiocarcinoma, Bile duct drainage, Stent