Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Cholangiocarcinoma

Biliary Tract Neoplasms

Bile Duct Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Biliary Tract Diseases

Gastrointestinal Diseases

Bile Duct Diseases

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Bile Duct Cancer

Biliary Tract Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Immune Checkpoint Inhibitors

Cisplatin

Durvalumab

Antineoplastic Agents, Immunological

Antimetabolites

Standard of care consisting of chemotherapy + durvalumab + endoscopic stenting

Standard of care consisting of chemotherapy + durvalumab + endoscopic stenting plus intraductal radiofrequency ablation (bRFA)

CICI (Gemcitabin d1 \& d8 Cisplatin d1 \& d8, Durvalumab d1) are administered repeating every 21 days for a total of 8 cycles.

Gemcitabin, Cisplatin and Durvalumab

Biliary Radiofrequency Ablation is applied at baseline, 6 and 12 weeks

Biliary Radiofrequency Ablation

ERCP with stenting are applied at baseline and as clinically indicated

Endoscopic Retrograde Cholangio-Pancreatography with stenting

Reiner Prof. Dr. med. Wiest

Martin Prof. Dr. med. Berger

The goal of this clinical trial is to provide evidence for the general tolerability of radiofrequency ablation (bRFA) in patients with unresectable bile duct cancer undergoing systemic palliative treatment consisting of chemotherapy (gemcitabine and cisplatin) plus durvalumab (immune-checkpoint-inhibitor, ICI). The main question it aims to answer is whether it is safe to combine chemotherapy (gemcitabine and cisplatin) and immunotherapy (durvalumab) - CICI therapy.

Participants will be assigned to either the control group or the experimental group. In the control group, the standard of care consists of endoscopy with stent placement in the bile duct and CICI, whereas in the experimental group, bRFA will be performed in addition to the standard of care. Participants will be followed up for 6 months, during the follow-up, the stage of the tumor, blood examination, the duration of the stent from the insertion until its failure, adverse events and quality of life will be examined.

Researchers will compare the standard of care alone to the experimental group to see if the additional bRFA procedure causes higher or no difference in adverse events rate.

Extrahepatic biliary tract cancer (EBTC) in most cases is diagnosed at an unresectable stage of disease. Standard-of-care systemic palliative treatment consists of chemotherapy (gemcitabine and cisplatin) plus durvalumab (immune-checkpoint-inhibitor, ICI). Nonetheless, overall survival remains limited at about 12.8 months. Moreover, severe adverse events can occur leading to treatment discontinuation increasing the risk of tumor progression and poor prognosis. Biliary obstruction is one of the most relevant factors for survival limiting eligibility and timing/dosing of chemo-immunotherapy. Endoscopic biliary stenting is standard to relieve jaundice, but tumor ingrowth can limit the rate and duration of success. Radiofrequency ablation (RFA) results from thermal damage created by a high-frequency alternating current released from an electrode into tissue. RFA has become a standard treatment modality in numerous indications, including the treatment of Barrett's oesophagus-related dysplasia and hepatocellular carcinoma. Intraductal biliary radiofrequency ablation (bRFA) is a relatively new method of inducing tumor necrosis via thermal energy. bRFA has been applied in patients suffering unresectable EBTC within randomized-controlled trials indicating improved stent patency as well as overall survival and progression-free survival.

The primary objective of the study is to provide evidence for the general tolerability of bRFA in patients with unresectable extrahepatic biliary tract cholangiocarcinoma undergoing CICI. It is hypothesis that bRFA is generally safe and well tolerated by patients. Primary endpoint of the study is any grade 3 or 4 adverse events leading to chemo-immune checkpoint inhibitor-therapy discontinuation up to six months after enrolment.

Eligible patients will be registered in the study database and randomized in 1:2 ratio to either the standard group (CICI with endoscopic biliary stenting) or the experimental bRFA group (CICI with endoscopic biliary stenting + bRFA).

CICI with endoscopic biliary stenting are standard of care applied commonly in both the control and the experimental group:

Endoscopic retrograde cholangiography (ERC) procedure stenting are applied at baseline and as clinically indicated. CICI cycle (Gemcitabin d1 \& d8, Cisplatin d1 \& d8, Durvalumab d1) are administered repeating every 21 days for a total of 8 cycles.

bRFA will be applied only to the experimental group, it is standardized as for generator settings and protocol adapting to tumor morphology using the probe at baseline, 6 and 12 weeks after study start.

Safety of Biliary Intraductal Radiofrequency Ablation in Patients With Unresectable Extrahepatic Biliary Tract Cancer

Safety of Biliary Intraductal Radiofrequency Ablation in Patients With Unresectable Extrahepatic Biliary Tract Cancer Undergoing Standard of Care Chemo-immune Checkpoint Inhibitor -Therapy: a Phase II, Multicenter, Randomized and Controlled

This will be planned only at study completion

This will be an investigator-initiated sub-study outside this protocol

AEs will be assessed according to US National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v5). Treatment discontinuation is defined as deferral of administration by at least four weeks or a definite stop of all CICI agents.

Current guideline definitions for cholangitis, post-ERCP pancreatitis and bleeding are applied. The rate of readmissions for biliary complications will be assessed specifically by being defined as any non-elective endoscopic reintervention after the first stent placement and will be documented in terms of timing, type of intervention, hospitalization and its duration and resolution.

EORTC QLQ-BIL21 (European Organisation for Research and Treatment of Cancer questionnaire for measuring quality of life in patients with cholangiocarcinoma and cancer of the gallbladder), scores range from 0 to 100, where a lower score means a better quality of life.

EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer questionnaire quality of life questionnaire core 30), scores range from 0 to 100, where a high scale score represents a higher response level.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Safety of Biliary Intraductal Radiofrequency Ablation in Patients With Unresectable Extrahepatic Biliary Tract Cancer	NCT06274879	Bile Duct Cance...	Gemcitabin, Cis... Biliary Radiofr... Endoscopic Retr...	18 Years -	Insel Gruppe AG, University Hospital Bern
Safety of Biliary Intraductal Radiofrequency Ablation in Patients With Unresectable Extrahepatic Biliary Tract Cancer	NCT06274879	Bile Duct Cance...	Gemcitabin, Cis... Biliary Radiofr... Endoscopic Retr...	18 Years -	Insel Gruppe AG, University Hospital Bern

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