Endobiliary Radiofrequency Ablation for Malignant Biliary Obstruction Due to Perihilar Cholangiocarcinoma

Study Overview
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Brief Summary
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A multicentre, parallel group, open label, randomized controlled trial comparing endobiliary RFA prior to metal stent placement with stent placement only in patients with inoperable perihilar cholangiocarcinoma.

Official Title
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Endobiliary Radiofrequency Ablation for Malignant Biliary Obstruction Due to Perihilar Cholangiocarcinoma: a Randomized Controlled Trial

Conditions
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Perihilar Cholangiocarcinoma

Intervention / Treatment
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* Device: Endobiliary radiofrequency ablation (eRFA)
* Device: uncovered self-expanding metal stent (uSEMS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older. Capable of providing written and oral informed consent. Histological or cytological proof of perihilar CCA (adenocarcinoma). Perihilar biliary obstruction with an indication for drainage with uSEMS.* Advanced (no candidate for surgical resection) due to metastases, vascular or lymph node (N2) involvement on imaging or during staging laparoscopy according to multidisciplinary team (MDT). Only patients with pCCA are eligible however in case of reasonable doubt between intrahepatic CCA with a perihilar biliary obstruction or massforming pCCA, patients can be included. Exclusion Criteria: Patients who potentially qualify for curative resection of pCCA. pCCA eligible for liver transplantation. Life-expectancy less than 3 months. ERCP and PTC technically not feasible. Uncontrolled coagulopathy (PTT >1,5x prolonged or thrombocytes below 40*10E9/L). Ongoing cholangitis or liver abscess. Patients are required to be off antibiotic treatment for cholangitis and/or liver abscess at least 7 days. Any condition that is unstable or that could jeopardize the safety of the subject and their compliance in the study. Patients who are pregnant or breastfeeding.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Endobiliary RFA + stent placement<br> | Device: Endobiliary radiofrequency ablation (eRFA)<br>* Intraductal radiofrequency ablation of tumor prior to stent placement<br>Device: uncovered self-expanding metal stent (uSEMS)<br>* Intraductal placement of uncovered metal stent<br>|
| Active Comparator: Stent placement only<br> | Device: uncovered self-expanding metal stent (uSEMS)<br>* Intraductal placement of uncovered metal stent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to biliary obstruction | Defined as period between initial procedure and recurrence of biliary obstruction. Recurrence of biliary obstruction is defined as recurrent jaundice (conjugated bilirubin ≥ 40 umol/l (≥2.3 mg/dl)), presence of biochemical evidence of cholestasis along with dilatation of the drained bile duct(s), or endoscopic findings suggesting stent occlusion. | Through study completion, max 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life expressed in quality adjusted life-years (QALYs) | EORTC QLQ-C30, BIL21 and EQ-5D questionnaires are to be filled out 4 weeks and every3 months after the intervention | Through study completion, max 1 year | 
| Number of patients with technical success of initial ablation | Defined as completion of ablation of the malignant stenosis through which the stent will be placed using RFA for 120 seconds with 7W. | During intervention | 
| Number of patients with functional success | In case of inadequate drainage prior to the procedure (bilirubin ≥40 umol/L [≥2.3 mg/dl]), defined as 50% decrease or normalization of bilirubin level within 14 days of the procedure or relieve of symptoms in case of cholangitis. In case of sufficient drainage prior to the procedure, a persistent bilirubin level <40 umol/L (<2.3 mg/dl) after 14 days is considered functional success. | 14 days | 
| Presumed reason of recurrent biliary obstruction | Stent occlusion due to tumour ingrowth Stent occlusion due to tumour overgrowth Stent occlusion due to sludge with/or without stones, hemobilia, food impaction Stent migration | Through study completion, an average of 1 year | 
| Need for unscheduled re-intervention (PTC and/or ERCP) to achieve adequate biliary drainage. |  | Through study completion, an average of 1 year | 
| Need for external drainage catheters. |  | Through study completion, an average of 1 year | 
| Time to re-intervention. |  | Through study completion, an average of 1 year | 
| Stent patency after repeated eRFA. |  | Through study completion, an average of 1 year | 
| Adverse events within 30 days after the procedu |  | 30 days | 
| Overall survival. |  | Through study completion | 
| Healthcare costs. |  | Through study completion, max 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endobiliary radiofrequency ablation, Stent patency