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

NCT06274879 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: 1938 Ablatio-bilicaSNCPT
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Bile Duct Cancer

Keywords

Durvalumab + chemotherapy; Radiofrequency ablation; Adverse events; Chemo-immune-checkpoint-inhibitor; Extra hepatic biliary tract cancer

Outcome Measures

Primary Outcomes (1)

• Any grade 3 or 4 adverse events (AE) leading to chemo-immune checkpoint inhibitor-therapy (CICI) 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 CICI agents.

  6 months

Secondary Outcomes (11)

• Endoscopic complications as measured by the Adverse events GastRointestEstinal Endoscopy (AGREE) criteria specifically developed for endoscopic interventions

  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

• 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

• 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

Other Outcomes (2)

• Details of adverse events

  6 months

• Overall survival at 24 months after randomization

  24 months

Study Arms (2)

Control arm

ACTIVE COMPARATOR

Standard of care consisting of chemotherapy + durvalumab + endoscopic stenting

Drug: Gemcitabin, Cisplatin and Durvalumab; Procedure: Endoscopic Retrograde Cholangio-Pancreatography with stenting

Biliary radiofrequency ablation

EXPERIMENTAL

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

Drug: Gemcitabin, Cisplatin and Durvalumab; Procedure: Biliary Radiofrequency Ablation; Procedure: Endoscopic Retrograde Cholangio-Pancreatography with stenting

Interventions

Gemcitabin, Cisplatin and Durvalumab DRUG

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

Biliary radiofrequency ablation; Control arm

Biliary Radiofrequency Ablation PROCEDURE

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

Biliary radiofrequency ablation

Endoscopic Retrograde Cholangio-Pancreatography with stenting PROCEDURE

ERCP with stenting are applied at baseline and as clinically indicated

Biliary radiofrequency ablation; Control arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 1.
• Adequate bone marrow function: Neutrophil count ≥1.0 x 109/L, platelet count ≥100 x 109/L.
• Adequate renal function: Estimated Glomerular Filtration Rate (eGFR) ≥50mL/min/1.73m2.
• Willing and able to provide written informed consent. \*The reason for inoperability needs to be documented and categorized as follows: - Locally advanced or vascular invasion = surgically not removable. - Distant metastasis.
• Severe comorbidities.

You may not qualify if:

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• 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.
• Received prior systemic treatment for unresectable and/or metastatic Extrahepatic Biliary Tract Cancer (EBTC).
• Any autoimmune diseases including inflammatory disorders such as Crohn's disease, ulcerative colitis, Wegener granulomatosis, systemic lupus erythematosus, rheumatoid arthritis, Graves' disease.
• Exceptions:
• Hypothyroidism following Hashimoto thyroiditis stable on hormone replacement.
• Patients with vitiligo.
• Any chronic skin disorders that do not require systemic treatment.
• Use of immunosuppressive medication within 3 weeks prior to the dose of durvalumab.
• Exceptions:
• \- Topical or inhaled steroids.
• \- Systemic corticosteroids at physiologic doses not exceeding \>10mg/d of prednisone or equivalent.
• Known history of Human Immunodeficiency Virus.
• Prior Self-Expandable Metal Stent (SEMS) placement.

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead
• Swiss Cancer League: collaborator

Study Sites (1)

Inselspital Bern University Hospital

Bern, Canton of Bern, 3010, Switzerland

Location

Related Publications (2)

• Kelley RK, Ueno M, Yoo C, Finn RS, Furuse J, Ren Z, Yau T, Klumpen HJ, Chan SL, Ozaka M, Verslype C, Bouattour M, Park JO, Barajas O, Pelzer U, Valle JW, Yu L, Malhotra U, Siegel AB, Edeline J, Vogel A; KEYNOTE-966 Investigators. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023 Jun 3;401(10391):1853-1865. doi: 10.1016/S0140-6736(23)00727-4. Epub 2023 Apr 16.

  PMID: 37075781 BACKGROUND

• Rimini M, Fornaro L, Lonardi S, Niger M, Lavacchi D, Pressiani T, Lucchetti J, Giordano G, Pretta A, Tamburini E, Pirrone C, Rapposelli IG, Diana A, Martinelli E, Garajova I, Simionato F, Schirripa M, Formica V, Vivaldi C, Caliman E, Rizzato MD, Zanuso V, Nichetti F, Angotti L, Landriscina M, Scartozzi M, Ramundo M, Pastorino A, Daniele B, Cornara N, Persano M, Gusmaroli E, Cerantola R, Salani F, Ratti F, Aldrighetti L, Cascinu S, Rimassa L, Antonuzzo L, Casadei-Gardini A. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer: An early exploratory analysis of real-world data. Liver Int. 2023 Aug;43(8):1803-1812. doi: 10.1111/liv.15641.

  PMID: 37452505 BACKGROUND

MeSH Terms

Conditions

Bile Duct Neoplasms

Interventions

Gemcitabine; Cisplatin; durvalumab; Stents

Condition Hierarchy (Ancestors)

Biliary Tract Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Prostheses and Implants; Equipment and Supplies

Study Officials

• Reiner Prof. Dr. med. Wiest

  Inselspital Bern University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Reiner Prof. Dr. med. Wiest

CONTACT

+41 31 632 59 41; reiner.wiest@insel.ch

Martin Prof. Dr. med. Berger

CONTACT

+41 31 632 41 14; martin.berger@insel.ch

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2024
• First Posted: February 23, 2024
• Study Start: June 1, 2025
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2028
• Last Updated: January 9, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)