Ablatio-bilica: safety of biliary intraductal radiofrequency ablation in patients with unresectable extrahepatic biliary tract cancer undergoing systemic anti-tumor therapy: a phase II, multi-center, randomized, and controlled study

Background Unresectable and/or metastatic extrahepatic biliary tract cancer (EBTC) presents a clinical challenge with high mortality rates despite therapeutic advancements, for example, chemotherapy + immune checkpoint inhibitors (CICI). One critical aspect is biliary obstruction, which compromises liver function, is associated with complications, and limits the applicability of systemic treatment (chemotherapy with or without ICI). Endoscopic interventions with stent placement alleviate biliary obstruction and, hence, are standard of care. However, stent patency issues and tumor progression remain challenges, prompting the exploration of adjunctive therapies. Biliary radiofrequency ablation (bRFA) induces local tumor destruction, improves stent patency, and potentially boosts the immune response against cancer cells, being synergistic with CICI. Randomized controlled trials (RCT) demonstrated improved overall survival in EBTC but have not been performed in the setting of CICI and have not focused on rate and severity of adverse events (AE). Nonetheless, multiple current meta-analyses propose the use of bRFA in malignant biliary obstruction without high-quality data on its safety in combination with CICI. Hypothesis We hypothesize that bRFA in patients with unresectable and/or metastatic EBTC undergoing systemic treatment (chemotherapy with or without immunotherapy) is safe. Methods This is a randomized-controlled clinical trial (RCT) comparing chemotherapy with or without ICI plus endoscopic stenting ( n = 12) versus chemotherapy with or without ICI plus endoscopic stenting and bRFA ( n = 24) being allocated in a 1:2 ratio. The primary endpoint is the proportion of severe treatment-related adverse events (grade 3 or 4) leading to permanent discontinuation of all active chemotherapeutic drugs up to six months after enrolment. Discussion Our findings will provide valuable insights into the role of bRFA as a supplementary treatment in unresectable and/or metastatic EBTC in conjunction with systemic treatment. In case this safety study does indicate no clinically relevant increase in severe adverse events in EBTC treated with systemic treatment, then an RCT addressing the efficacy of bRFA in terms of progression-free and overall survival in this setting will follow. Clinical Trial Registration ClinicalTrials.gov , identifier NCT06274879.