Endobiliary Radiofrequency Ablation With S-1 for Unresectable Cholangiocarcinoma

Study Overview
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Brief Summary
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Endobiliary radiofrequency ablation (RFA) with biliary stent has been reported to be a beneficial treatment option for palliation of malignant biliary strictures. RFA uses a high-frequency alternating current to generate heat and achieve coagulative necrosis when in contact with tissue. Within the bile duct, RFA appears to be safe and may result in decreased tumor ingrowth. However, most of therapeutic effects were expected to delay bile duct obstruction rather than to decrease the tumor. Recently orally available chemotherapeutic agent, S-1, an oral fluoropyrimidine, was reported as effective in patients with bile duct adenocarcinoma. To date, little is known about the role of the addition of systemic chemotherapy to RFA for cholangiocarcinoma. The aim of this study is to evaluate the combined effect of RFA and S-1 in patients with unresectable cholangiocarcinoma.

Detailed Description
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Over 60 % of common bile duct (CBD) obstructions are due to malignancy, and the majority of neoplasms are unresectable at the time of diagnosis. Biliary drainage with placement of metal or plastic stents for palliation is the therapy of choice in this set of patients. Radiofrequency ablation (RFA) is well established method for treatment of some solid tumors, like liver cancer, lung cancer, etc. Recently, an endoscopically applicable radiofrequency probe, HabibTM EndoHBP catheter, was approved for clinical use. RFA uses a high-frequency alternating current to generate heat and achieve coagulative necrosis when in contact with tissue. Many studies showed RFA with biliary stent was a beneficial treatment option for palliation of malignant biliary strictures. However, most of therapeutic effects were expected to delay bile duct obstruction rather than to decrease the tumor. Recently orally available chemotherapeutic agent, S-1, an oral fluoropyrimidine, was reported as effective in patients with bile duct adenocarcinoma. To date, little is known about the role of the addition of systemic chemotherapy to RFA for cholangiocarcinoma. The aim of this study is to conduct a randomised, controlled, clinical trial to compare the effect of S-1 plus RFA with stent with RFA with stent in patients with unresectable cholangiocarcinoma.

Official Title
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Endobiliary Radiofrequency Ablation With S-1 in Patients With Unresectable Cholangiocarcinoma: A Prospective Randomized Trial With Open Label Control

Conditions
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Cholangiocarcinoma

Intervention / Treatment
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* Device: radiofrequency ablation
* Drug: S-1
* Device: Stent


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Obtention of a written informed consent. Patient over 18. Patient with histologically proved cholangiocarcinoma ; histologic diagnosis must be proved by biliary brushing, bile cytology, endobiliary biopsy under Spyglass, or by EUS-FNA. Patient with Karnofsky score ≥ 50 % Patient capable of fill in the quality of life questionnaire. Exclusion Criteria: No written informed consent. Patients under or already treated by radiotherapy or chemotherapy treatment for cholangiocarcinoma. Patients with porphyria or hypersensibility to porphyrins. Pregnant, parturient or breastfeeding women. Patient under 18.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RFA+stent+S-1<br>Endoscopic retrograde cholangiopancreatography (ERCP) would be performed under standard operating conditions to confirm the biliary malignancy. Patients will receive endobiliary radiofrequency ablation ( RFA) followed by plastic stent(s) placement, and be treated with S-1 began within 1 month after RFA. | Device: radiofrequency ablation<br>* All patients underwent biliary sphincterotomy. Cholangiogram was performed to confirm stricture location, length and diameter. The Habib Endo HPB (Hepatobiliary) probe (EMcision, HitchinHerts, UK) was then advanced over a wire at the level of the biliary stricture and ablation using ERBE generator set at 7-10 watts for a time period of 90-120 s was conducted. A 1- to 2-min resting period after energy delivery was allowed before moving the catheter along the length of the stricture to ablate the rest of the stricture.<br>Drug: S-1<br>* In the RFA plus S-1 group, treatment with S-1 began within 1 month after RFA. Based on the patient's body surface area, S-1 was administered as follows: when the level of total bilirubin was less than 2 mg/dl. Based on the body surface area, S-1 was administered if <1.25 m2, 80 mg/day; if 1.25-1.5 m2, 100 mg/day; if≥1.5 m2, 120 mg/day. S-1 was administered orally twice daily for 14 days, followed by 7 days without treatment.<br>* Other names: oral fluoropyrimidine;Device: Stent<br>* Plastic stent(s) were placed after RFA depending on the location of the malignant obstruction<br>|
| Placebo Comparator: RFA+stent<br>Endoscopic retrograde cholangiopancreatography (ERCP) would be performed under standard operating conditions to confirm the biliary malignancy. Patients will only receive endobiliary radiofrequency ablation ( RFA) followed by plastic stent(s) placement | Device: radiofrequency ablation<br>* All patients underwent biliary sphincterotomy. Cholangiogram was performed to confirm stricture location, length and diameter. The Habib Endo HPB (Hepatobiliary) probe (EMcision, HitchinHerts, UK) was then advanced over a wire at the level of the biliary stricture and ablation using ERBE generator set at 7-10 watts for a time period of 90-120 s was conducted. A 1- to 2-min resting period after energy delivery was allowed before moving the catheter along the length of the stricture to ablate the rest of the stricture.<br>Device: Stent<br>* Plastic stent(s) were placed after RFA depending on the location of the malignant obstruction<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| survival time | Compare overall survival time in patients with unresectable cholangiocarcinoma treated with RFA combined with or without S-1 | two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adverse events | Number of participants with adverse events; type, frequency and intensity of adverse events | two years | 
| frequency of repeat RFA |  | two years | 
| the frequency of cholangitis |  | two years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Biliary duct carcinoma;, radiofrequency ablation, S-1