RFA Combined With Chemotherapy for Unresectable Cholangiocarcinoma

Study Overview
=================
Brief Summary
-----------------
Extrahepatic cholangiocarcinoma is a malignant tumor that is highly malignant and difficult to diagnose and treat early. Endobiliary radiofrequency ablation (RFA) has been reported to be a beneficial treatment option for palliation of malignant biliary strictures. Within the bile duct, RFA appears to be safe and may result in decreased tumor ingrowth. 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 compare the efficacy and safety of RAF combined with Gemcitabine and S-1 in patients with unresectable cholangiocarcinoma.

Detailed Description
-----------------
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 compare the efficacy and safety of RAF combined with Gemcitabine and S-1 in patients with unresectable cholangiocarcinoma

Official Title
-----------------
Endoscopic Radiofrequency Ablation Combined With Gemcitabine and S-1 in Paitiens for Unresectable Cholangiocarcinoma：A Randomized Open-label Clinical Trial

Conditions
-----------------
Cholangiocarcinoma

Intervention / Treatment
-----------------
* Device: radiofrequency ablation
* Drug: Chemotherapy drug


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Obtention of a written informed consent. 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 > 60， ECOG>level 2 Patient capable of fill in the quality of life questionnaire For the first time treatment CT, MRCP, EUS and other examinations indicate that the tumor has locally infiltrated large blood vessels and cannot be surgically removed Exclusion Criteria No written informed consent Patients under or already treated by radiotherapy or chemotherapy treatment for cholangiocarcinoma. Pregnant, parturient or breastfeeding women Serious abnormalities in liver and kidney function and coagulation function The ERCP guide wire cannot pass the stricture due to severe biliary stricture Merge with other malignant tumors Use other treatments that may affect the observation, such as radioactive particles or seed stent implantation, P53 injection, oral chemotherapy, interventional therapy, etc.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RAF combined with gemcitabine and S-1 group<br>Patients will receive endobiliary radiofrequency ablation ( RFA) followed by plastic stent(s) placement, and be treated with gemcitabine and S-1 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. Plastic stent(s) were placed after RFA depending on the location of the malignant obstruction<br>Drug: Chemotherapy drug<br>* Gemcitabine 1 000 mg/m2 intravenously on day 1，8; S-1 80 mg/m2 was taken orally twice for two weeks. The curative effect was evaluated comprehensively for each 2 cycles of chemotherapy<br>* Other names: oral fluoropyrimidine;|
| Placebo Comparator: RFA-only gruop<br>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. Plastic stent(s) were placed after RFA depending on the location of the malignant obstruction<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| survival time | The period from endoscopic treatment to patient death or the last day of study | 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 | one month | 
| Stent patency time | Take the stent placement as the starting point and the stent occlusion confirmed by ERCP as the end point. Record the time interval between the two point | two years | 
| Progression free survival | evaluate the survival time without disease progression | two years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
S-1, biliary tract cancer, radiofrequency ablation, Gemcitabine