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 systemic anti-tumor therapy with or without immune-checkpoint-inhibitor (ICI). The main question it aims to answer is whether it is safe to combine systemic anti-tumor therapy with or without ICI with and bRFA.
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 systemic anti-tumor therapy, 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.
Male or female ≥18 years old.
Histologically or cytologically confirmed diagnosis of previously untreated and unresectable*, locally advanced and/or metastatic extrahepatic biliary tract cholangiocarcinoma with obstructive jaundice (increased serum level of total bilirubin).
ECOG performance status 0 to 2.
Adequate bone marrow function: Neutrophil count ≥1.0 x 109/L, platelet count ≥100 x 109/L.
Solely intrahepatic cholangiocarcinoma or mixed type liver tumors (cholangiocarcinoma with hepatocellular differentiation parts).
Multiple hepatic metastases with significant blockage of one or more liver segments and/or less than 50% of liver parenchyma potentially drainable on pre-intervention imaging.
In case of immune-checkpoint-inhibitor (ICI) administration, any autoimmune diseases including inflammatory disorders such as Crohn's disease, ulcerative colitis, Wegener granulomatosis, systemic lupus erythematosus, rheumatoid arthritis, Graves' disease.
Use of immunosuppressive medication within 3 weeks prior to ICI administration.
Parallel
Gemcitabin, Cisplatin and Durvalumab
DrugCICI (Gemcitabin d1 \& d8 Cisplatin d1 \& d8, Durvalumab d1) are administered repeating every 21 days for a total of 8 cycles.
Biliary Radiofrequency Ablation
Procedure/SurgeryBiliary Radiofrequency Ablation is applied at baseline, 6 and 12 weeks
Endoscopic Retrograde Cholangio-Pancreatography with stenting
Procedure/SurgeryERCP with stenting are applied at baseline and as clinically indicated
Any grade 3 or 4 adverse events (AE) leading to systemic anti-tumor therapy with or without ICI discontinuation up to six months after randomization.
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 systemic anti-tumor therapy with or without ICI agents.
Endoscopic complications as measured by the Adverse events GastRointestEstinal Endoscopy (AGREE) criteria specifically developed for endoscopic interventions
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.
Progression-free survival: The time until either progression of the underlying disease or death, whichever occurs first, assessed from the time of up to 6 months after randomization.
Death from any cause at the follow-up at 6 months after randomization (overall survival).
Disease-specific quality-of-life as measured by the EORTC QLQ-BIL21 before every CICI cycle and at 3 and 6 months after the start of CICI treatment.
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.
Details of adverse events
Overall survival at 24 months after randomization
This will be an investigator-initiated sub-study outside this protocol
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Insel Gruppe AG, University Hospital Bern
Lead sponsor
Swiss Cancer League
Collaborator
