Efficacy and Safety Study of PDT Using Deuteporfin for Unresectable Advanced Perihilar Cholangiocarcinoma

Study Overview
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Brief Summary
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This is a multi-center, randomized, controlled, open-label, phase IIa clinical study.The study will observe the efficacy and safety of Deuteporfin photodynamic therapy in addition to stenting compared to stenting alone in patients with unresectable advanced Perihilar Cholangiocarcinoma.

Official Title
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Multi-center, Randomized, Controlled, Open-label Study of Deuteporfin Photodynamic Therapy Plus Stenting Versus Stenting Alone as Treatment for Unresectable Advanced Perihilar Cholangiocarcinoma

Conditions
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Hilar Cholangiocarcinoma

Intervention / Treatment
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* Combination Product: PDT-Deuteporfin（6 hour)
* Combination Product: PDT-Deuteporfin（9 hour)
* Device: stenting


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females aged 18 or older. Diagnosed with radiologically and biopsy or cytology confirmed inoperable perihilar cholangiocarcinoma Bismuth Tumor Stage Ⅲ/Ⅳ. KPS≥70. Total Bilirubin<85.5 umol/L. Informed consent obtained. Exclusion Criteria: The first diagnosis time of cholangiocarcinoma > 3 months before randomization. Expected survival <3 months. Patients with abnormal laboratory parameters: white blood cell<3.0×10(9)/L；hemoglobin <80g/L；Neutrophil Differential Count<1.5×10(9)/L；blood platelets<75×10(9)/L；or patients have other diseases of the blood system. Creatinine clearance >1.5×upper limit of normal range. Patients with severe liver function damage，or aspartate transaminase (AST) and/or alanine transaminase (ALT) >5×upper limit of normal range. Patients have intrahepatic metastasis, or distant metastasis (including distant lymph node metastasis); or bile duct cancer patients with other parts of the primary malignant tumor. Patients have activities of viral hepatitis, liver cirrhosis, liver abscess, alcoholic fatty liver, primary hepatocellular carcinoma, and other liver diseases; or patients have immunoglobulin G4 (IgG4) sclerosing cholangitis, primary sclerosing cholangitis, autoimmune cholangitis, and other cholangitis. Malignancies other than cholangiocarcinoma within 5 years prior to randomization, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer. Patients had received PDT treatment prior to randomization. Patients had received bile duct carcinoma resection prior to randomization. Patients had received chemotherapy, or brachytherapy，or radiotherapy prior to randomization. Patients had received metal stent treatment prior to randomization. Presence of infection (active, untreated infection and/or acute bacterial or fungal infection) other than the infection of the bile duct (cholangitis). Uncontrolled severe hypertension [sitting systolic blood pressure (SBP) >180 mmHg and/or sitting diastolic blood pressure (DBP) >110 mmHg after medication]; have severe complications of hypertension or diabetes. Presence of severe heart, lung and central nervous system diseases. Presence of mental illness, or mental disorders can not accurately describe their feelings, or not according to the doctor's advice to take medication. History of alcohol abuse, drug abuse in the past 1 years. Presence of allergic diseases，or known to have light skin allergies or porphyria, or known to allergic to study drug(porphyrin drugs) or other similar compounds, cephalosporin antibiotics, other types penicillin, β lactamase inhibitors. Patients need to use prohibited drugs in proposal during the first 2 weeks of screening, or during the trial period. Patients having been enrolled in other clinical trial within 3 months prior to this clinical trial. Pregnant, lactating women or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception. The researchers weren't allowed to participate in this study as subjects. Patients unsuitable for enrollment in the clinical trial according to investigators decision.

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PDT-Deuteporfin（6 hour）plus stenting<br>Deuteporfin (7.5mg/kg) was injected intravenously 6 hours before intraluminal photoactivation (wavelength,630 nm;light dose, 180 J/cm(2)). After PDT, endoscopic or percutaneous stenting will be performed.The second treatment may be given after 3 months. | Combination Product: PDT-Deuteporfin（6 hour)<br>* Photodynamic therapy (PDT) involves the i.v. injection of Deuteporfin (7.5 mg/kg，Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co., Ltd，Shanghai，China） followed by the illumination of the tumor. 6 hours after the injection,a laser light ( (wavelength,630 nm; light dose, 180 J/cm(2)；Guilin Xingda Photoelectric Medical Calinstrument Co., Ltd，,Fujian, China） will be applied to the tumor.The second courses of PDT may be given at 3-month intervals.<br>Device: stenting<br>* The stenting procedure consists in the placement of plastic stents （Boston Scientific Corporation, MA,USA；or Cook Medical, Bloomington,USA）above the main tumors of the right and left hepatic bile ducts via endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC).<br>|
| Experimental: PDT-Deuteporfin（9 hour）plus stenting<br>Deuteporfin (7.5mg/kg) was injected intravenously 9 hours before intraluminal photoactivation (wavelength,630 nm;light dose, 180 J/cm(2)). After PDT, endoscopic or percutaneous stenting will be performed.The second treatment may be given after 3 months. | Combination Product: PDT-Deuteporfin（9 hour)<br>* Photodynamic therapy (PDT) involves the i.v. injection of Deuteporfin (7.5 mg/kg，Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co., Ltd，Shanghai，China) followed by the illumination of the tumor.9 hours after the injection,a laser light ( (wavelength,630 nm; light dose, 180 J/cm(2)；Guilin Xingda Photoelectric Medical Calinstrument Co., Ltd，,Fujian, China) will be applied to the tumor. The second courses of PDT may be given at 3-month intervals.<br>Device: stenting<br>* The stenting procedure consists in the placement of plastic stents （Boston Scientific Corporation, MA,USA；or Cook Medical, Bloomington,USA）above the main tumors of the right and left hepatic bile ducts via endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC).<br>|
| Other: Stenting<br>Endoscopic or percutaneous stenting alone will be performed. | Device: stenting<br>* The stenting procedure consists in the placement of plastic stents （Boston Scientific Corporation, MA,USA；or Cook Medical, Bloomington,USA）above the main tumors of the right and left hepatic bile ducts via endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overallsurvival | From the date of randomization until the date of death or the last date the subject was known to be alive | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-year survival rate | From the date of randomization until the date of death or the last date the subject was known to be alive | Up to 12 months | 
| The change rate of Bile duct stricture | The date at the phase of baseline，at the end of first month, third month and sixth month | Up to 6 months | 
| The change rate of serum bilirubin | The date at the phase of baseline，at the first week ，at the end of first month | Up to 1 month | 
| The change rate of carbohydrate antigen 199(CA199) | The date at the phase of baseline，at the end of first month, third month and sixth month | Up to 6 months | 
| The change rate of Karnofsky Performance Scale(KPS) | From the date of randomization until the date of death or the last date the subject was known to be alive | Up to 12 months | 
| The change rate of European Organization for Research and Treatment of Cancer Quality Of Life Questionnaire C30 (EORTC QLQ-C30) | From the date of randomization until the date of death or the last date the subject was known to be alive | Up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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photodynamic therapy(PDT), stenting, Hilar Cholangiocarcinoma, Deuteporfin