Endoscopic Radiofrequency Ablation for Unresectable Cholangiocarcinoma

Study Overview
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Brief Summary
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The goal of this clinical trial is to learn about radiofrequency ablation in patients with unresectable bile duct cancer who receive systemic chemotherapy and bile duct stenting. The main questions it aims to answer are: Does radiofrequency ablation of tumorous bile duct occlusion reduce risk of complications in these patients (eg stent dysfunction, delay of chemotherapy, infections etc)? Is radiofrequency ablation safe in these patients? All participants will receive standard treatment with systemic chemotherapy and bile duct stenting. Researchers will compare two groups (one group will receive additional radiofrequency ablation, the other not).

Official Title
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Radiofrequency Ablation Via Catheter and Transpapillary Access in Patients With Cholangiocarcinoma

Conditions
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Cholangiocarcinoma, Klatskin Tumor, Bile Duct Cancer, Liver Cancer

Intervention / Treatment
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* Procedure: Intraductal biliary radiofrequency ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Unresectable perihilar and/or ductal CCA with bile duct stenting and palliative systemic therapy as indicated by the local Multidisciplinary Team (MDT) Written informed consent Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Age ≥18 years Eligibility for palliative systemic therapy based on clinical and laboratory parameters (except hyperbilirubinemia) as determined by the local MDT No prior radiofrequency ablation (RFA) for CCA No repeated bile duct stenting in the past 3 months (trial inclusion is possible upon first stent replacement or initial stent placement within past 3 months) No concomitant disease or malignancy interfering with the study procedure or efficacy outcome measures, particularly no severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV, unstable angina pectoris, myocardial infarction within ≤3 months, significant arrhythmias) and no psychiatric disorders precluding understanding of information of trial related topics and giving informed consent

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 |
| --- | --- |
| Active Comparator: Arm A: ablation arm<br>Systemic chemotherapy and bile duct stenting with intraductal RFA of malignant bile duct obstructions employing a CE-certified ablation catheter prior to stent placement. | Procedure: Intraductal biliary radiofrequency ablation<br>* Radiofrequency ablation via catheter and transpapillary access of malignant bile duct obstruction<br>* Other names: RFA;|
| No Intervention: Arm B: control arm<br>Systemic chemotherapy and bile duct stenting without RFA. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first event, ie stent dysfunction | • Time-to-first event (during 6 months follow up), i.e. stent dysfunction defined by bilirubin >5 mg/dl and/or cholangitis (fever >38.5°C and/or increase in C-reactive protein by at least 3-fold upper limit of normal and at least 20% from baseline without extrahepatic focus and absence of tumor progression) leading to premature stent replacement and/or disruption of chemotherapy (all possible events will be reviewed by a blinded and independent Endpoint Review Committee [ERC].) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Time to death or last seen alive | up to 30 month | 
| Satisfaction assessed by EORTC QLQ-C30 questionnaire | The EORTC QLG Core Questionnaire (EORTC QLQ-C30) is a 30-item instrument designed to measure quality of life in cancer patients. It is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. | 6 months | 
| Satisfaction assessed by EORTC QLQ-BIL21 questionnaire | The EORTC QLQ-BIL21 consists of 21 questions: 3 single-item assessments relating to treatment side effects, difficulties with drainage bags/tubes and concerns regarding weight loss, in addition to 18 items grouped into 5 proposed scales: eating symptoms (4 items), jaundice symptoms (3 items), tiredness (3 items), pain symptoms (4 items) and anxiety symptoms (4 items). The response format is a four-point Likert scale.and designed to more specifically adress side effects. A high scale score represents a higher response level. | 6 months | 
| Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE V5 | Safety events | 6 months | 
| Clinical event rate at 6 months | Rate of clinical events defined as per primary outcome after 6 months follow up | 6 months | 
| Total days of overnight-hospital-stays | Total days of overnight-hospital-stays | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radiofrequency ablation, Intraductal, Biliary, Endoscopic retrograde cholangiography, Transpapillary, Stent dysfunction, Cholangitis, Obstruction