REMS Combined With TAI for Unresectable HC

Study Overview
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Brief Summary
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The purpose of this randomized controlled study is to evaluate the efficacy and safety of the Radiation-Emitting Metallic Stents (REMS) combined with Trans-Arterial Infusion (TAI) for unresectable hilar cholangiocarcinoma.

Detailed Description
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This is a multicentric, open-labal, randomized controlled trial which aims to evaluate the efficacy and safety of Radiation-Emitting Metallic Stents (REMS) combined with Trans-Arterial Infusion (TAI) versus Uncovered Self-Expandable Metallic Stent (SEMS) Combined With Trans-Arterial Infusion (TAI) for Unresectable Hilar Cholangiocarcinoma. The primary hypotheses are that Radiation-Emitting Metallic Stents (REMS) combined with Trans-Arterial Infusion (TAI) is superior to Uncovered Self-Expandable Metallic Stent (SEMS) Combined With Trans-Arterial Infusion (TAI) with respect to Over survival(OS). The primary endpoint is overall survival. The secondary endpoints include quality of life, progression free survival, relief of jaundice, patency, and adverse events.

Official Title
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Radiation-Emitting Metallic Stents (REMS) Combined With Trans-Arterial Infusion (TAI) Versus Uncovered Self-Expandable Metallic Stent (SEMS) Combined With Trans-Arterial Infusion (TAI) for Unresectable Hilar Cholangiocarcinoma

Conditions
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Unresectable Hilar Cholangiocarcinoma

Intervention / Treatment
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* Procedure: REMS+TAI
* Procedure: SEMS+TAI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinically or histopathologically diagnosis of cholangiocarcinoma With symptoms such as jaundice related to biliary obstruction Biliary obstruction of Bismuth-Correlate Classification Type III or IV Unresectable disease confirmed by multidisciplinary team Maximum diameter of lesion ≤3 cm Liver function of Child-Pugh A or B 18 years older With an expected survival time ≥ 3 months With an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 Meet the following laboratory test parameters: hematologic function (absolute neutrophil count ≥ 1.0×10⁹/L; platelet count ≥ 50×10⁹/L; hemoglobin ≥ 90 g/L; INR < 1.7 or prolonged prothrombin time not more than 4 seconds); liver function (ALT/AST not more than 5 times the upper limit of normal; albumin ≥ 28 g/L); renal function (serum creatinine not more than 1.5 times the upper limit of normal) Exclusion Criteria: Presence of distant metastases With another malignancy type other than cholangiocarcinoma Previous history of biliary stent placement Moderate to severe ascites (ascites up to Child-Pugh score of 3) Biliary perforation History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to enrollment Unstable angina, myocardial infarction, coronary artery bypass graft, congestive heart failure, cerebrovascular accident (including transient ischemic attack, pulmonary embolism) within 3 months before enrollment Persistent arrhythmia (CTCAE criteria grade 2 and above), atrial fibrillation of any degree, prolonged Qtc interval (more than 450 ms in men and more than 470 ms in women) Refractory hypertension (blood pressure above 150/100 mmHg even after optimal drug therapy Concomitant receipt of other anti-tumor drugs Concomitant human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome Pregnant or lactating women Concomitant acute or chronic mental disorders (including mental disorders affecting subject enrollment, therapeutic intervention, and follow-up)

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: REMS+TAI<br>Radiation-Emitting Metallic Stents (REMS) Combined With Trans-Arterial Infusion (TAI) for Unresectable Hilar Cholangiocarcinoma | Procedure: REMS+TAI<br>* Radiation-Emitting Metallic Stents (REMS) Combined With Trans-Arterial Infusion (TAI) for Unresectable Hilar Cholangiocarcinoma<br>|
| Active Comparator: SEMS+TAI<br>Uncovered Self-Expandable Metallic Stent (SEMS) Combined With Trans-Arterial Infusion (TAI) for Unresectable Hilar Cholangiocarcinoma | Procedure: SEMS+TAI<br>* Uncovered Self-Expandable Metallic Stent (SEMS) Combined With Trans-Arterial Infusion (TAI) for Unresectable Hilar Cholangiocarcinoma<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Time from treatment to the day when the patients died or lost to the follow-up. | Participants will be followed till die or lost to follow-up, an expected average of a year. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Including side effect/complication, radioactive safety. Complications would be evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE 4.03). | Participants will be followed till die or lost to follow-up, an expected average of a year. | 
| Relief of jaundice | Relief of jaundice was defined as reduction of more than 20% total bilirubin within 1 week after stent implantation. | Relief of jaundice was evaluated within 1 week after stent implantation. | 
| Patency | Time from stent placement to the day when re-stenosis of the stent occurred. | Participants will be followed till die or lost to follow-up, an expected average of a year. | 
| Quality of life assessed by Quality-of-life Questionnaire Core 30 | Quality of life was assessed by European Organization for Research and Treatment of Cancer (EORTC) Quality-of-life Questionnaire Core 30 (QLQ-C30), which was completed at different time points: baseline (T0), 4 weeks (T1), 12 weeks (T2), and 24 weeks (T3) after stenting procedures. | 24 weeks | 
| Time to symptom progression | Symptom progression was defined as when ECOG performance status increased from 0-2 before enrollment to 4 or 5 | Participants will be followed till progression appeared or die or lost to follow-up, an expected average of a year. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Unresectable hilar cholangiocarcinoma, Irradiation stent, Conventional stent, Trans-arterial infusion, Bile duct