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
Overview
- Phase
- Phase 2
- Intervention
- Gemcitabin, Cisplatin and Durvalumab
- Conditions
- Bile Duct Cancer
- Sponsor
- Insel Gruppe AG, University Hospital Bern
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- Any grade 3 or 4 adverse events (AE) leading to chemo-immune checkpoint inhibitor-therapy (CICI) discontinuation up to six months after randomization.
- Status
- Not yet recruiting
- Last Updated
- last year
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Control arm
Standard of care consisting of chemotherapy + durvalumab + endoscopic stenting
Intervention: Gemcitabin, Cisplatin and Durvalumab
Control arm
Standard of care consisting of chemotherapy + durvalumab + endoscopic stenting
Intervention: Endoscopic Retrograde Cholangio-Pancreatography with stenting
Biliary radiofrequency ablation
Standard of care consisting of chemotherapy + durvalumab + endoscopic stenting plus intraductal radiofrequency ablation (bRFA)
Intervention: Gemcitabin, Cisplatin and Durvalumab
Biliary radiofrequency ablation
Standard of care consisting of chemotherapy + durvalumab + endoscopic stenting plus intraductal radiofrequency ablation (bRFA)
Intervention: Biliary Radiofrequency Ablation
Biliary radiofrequency ablation
Standard of care consisting of chemotherapy + durvalumab + endoscopic stenting plus intraductal radiofrequency ablation (bRFA)
Intervention: Endoscopic Retrograde Cholangio-Pancreatography with stenting
Outcomes
Primary Outcomes
Any grade 3 or 4 adverse events (AE) leading to chemo-immune checkpoint inhibitor-therapy (CICI) discontinuation up to six months after randomization.
Time Frame: 6 months
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.
Secondary Outcomes
- Endoscopic complications as measured by the Adverse events GastRointestEstinal Endoscopy (AGREE) criteria specifically developed for endoscopic interventions(6 months)
- 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.(6 months)
- Stent patency at month 3 visit and at 6 months after the start of CICI treatment.(6 months)
- Number of patients with any grade 3 or 4 Adverse Events (AE) leading to discontinuation or non-initiation of CICI up to six months after randomization.(6 months)
- Number of patients not starting CICI within 4 weeks after randomization.(6 months)
- Change in health-related quality-of-life at baseline, 3 and 6 months from the start of the CICI treatment as measured by the EORTC QLQ-C30(6 months)
- Number of courses of CICI applied(6 months)
- Total dose of CICI applied(6 months)
- Time from randomization to CICI start.(6 months)
- 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.(6 months)
- Death from any cause at the follow-up at 6 months after randomization (overall survival).(6 months)