Treatment of Non-resectable Bile Duct Cancer with Radiofrequency Ablation or Photodynamic Therapy

Phase 4

Recruiting

• Conditions: Hilar Cholangiocarcinoma
• Interventions: Drug: Photosensitizer; Procedure: Radiofrequency ablation (RFA)

• Registration Number: NCT05551299
• Lead Sponsor: University of Leipzig

Brief Summary

Bile duct cancer is often diagnosed after curative options are no longer available. Stent therapy is used to keep the ducts open and can be combined with photodynamic therapy (PDT) to extend life expectancy. PDT requires an injection of photosensitizer after which light of a particular wavelength is applied endoscopically to kill the cancer cells. Drawbacks include not only high costs and poor availability, but foremost that patients have to avoid direct sunlight for a period of weeks. Radio frequency ablation (RFA) together with stent implantation constitutes an alternative by which the cancer cells are killed through heat, also applied endoscopically. The RFA technology is more widely available and easier to deploy. However, it has not been studied extensively and no randomized trials exist comparing the two methods. This trial will compare survival in patients with a particular bile duct cancer depending on whether they receive PDT or RFA. Moreover, data will be collected on side-effects and quality of life.

Detailed Description

Klatskin tumours are a form of bile duct cancer. They are generally not diagnosed until quite late and a curative operation is rarely a possibility. Their anatomic location usually results in bile duct obstruction and the aim of therapy is thus to keep the ducts open. This is accomplished through endoscopic retrograde cholangiopancreatography (ERCP) by implanting stents. Stent therapy combined with photodynamic therapy (PDT) extends life expectancy. PDT requires an injection of photosensitizer that is absorbed primarily by the cancer cells. Light of a particular wavelength is then applied with ERCP to kill the cancer cells. Drawbacks include not only high costs and poor availability, but foremost that patients have to avoid direct sunlight for a period of weeks. Radio frequency ablation (RFA) together with stent implantation constitutes an alternative by which the cancer cells are killed through heat applied during ERCP. The RFA technology is more widely available and easier to deploy. However, it has not been studied extensively and no randomized trials exist comparing the two methods. This trial will compare survival in patients with Klatskin tumours depending on whether they receive PDT or RFA. Moreover, data will be collected on side-effects and quality of life.

Study Timeline

• Study First Submitted: 2022-09-08
• Study First Submitted QC: 2022-09-20
• Study First Posted: 2022-09-22
• Study Start: 2023-02-10
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-24
• Last Update Posted: 2025-03-27
• Primary Completion: 2028-04
• Study Completion: 2028-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 258

Inclusion Criteria

1. Hilar cholangiocarcinoma (cytological or histological confirmation)
2. Surgery is not planned
3. Age ≥ 18 years
4. Written informed consent

Exclusion Criteria

1. Tumour not accessible endoscopically
2. Known hypersensitivity to porphyrins or to any of the other ingredients of the photosensitizer chosen
3. Leukopenia (< 2000/mm3)
4. Thrombocytopenia (< 100,000 / mm³)
5. Severe, uncorrected coagulopathy (at the discretion of the physician)
6. Suspected erosion of major blood vessels, because of the risk of life-threatening mass haemorrhage exists
7. Porphyria (clinician's assessment) or other light-exacerbated diseases
8. Severely impaired liver and or kidney function (at the discretion of the physician)
9. Bedridden for more than 50% of the time (similar to ECOG (Eastern Cooperative Oncology Group) grade 3)
10. Planned surgical procedure within the next 30 days
11. Concurrent eye disease that will require a slit lamp examination within the next 30 days
12. Prior radiotherapy within the last four weeks
13. Previous PDT or RFA
14. Planned liver transplantation
15. Fertile women (within two years of their last menstruation) without appropriate contraceptive measures (implanon, injections, oral contraceptives, intrauterine devices, partner with vasectomy) while participating in the trial (participants using a hormone-based method have to be informed of possible effects of the trial medication on contraception)
16. Participation in other interventional trials
17. Patients under legal supervision or guardianship
18. Pregnant or nursing women

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Photodynamic therapy (PDT)	Photosensitizer	The index procedure in all patients at baseline includes stenting, using an endoscopic retrograde cholangio-pancreatography (ERCP) procedure. The Intervention is at least one PDT at baseline according to the clinical routine of the trial site.
Radiofrequency ablation (RFA)	Radiofrequency ablation (RFA)	The index procedure in all patients at baseline includes stenting, using an endoscopic retrograde cholangio-pancreatography (ERCP) procedure. The Intervention is at least one RFA at baseline according to the clinical routine of the trial site.

Primary Outcome Measures

Name	Time	Method
Overall survival	through study completion, an average of 1 year	Hazard ratio from a Cox regression model will be used to compare randomization arms. Covariates will be stratification variables, classification of local inoperability, use of prophylactic antibiotics, Bismuth type and time between diagnosis and beginning RFA/PDT.

Secondary Outcome Measures

Name	Time	Method
Overall survival (complementary perspective: restricted mean survival on a time horizon of two-years)	through study completion, an average of 1 year	Kaplan-Meier estimates will be used (see e.g. PMID: 15690989)
Stent patency based on clinician's assessment (e.g. cholangitis, cholestasis, ultrasound)	through study completion, an average of 1 year	Stent patency provides one measure of the burden of the disease and efficacy of the treatment. Mean time to stent closure/replacement/death after last stent replacement will be analysed.
Quality-adjusted life years (QALYs)	through study completion, an average of 1 year	Using QALYs, a weighted measure of survival will be compared between RFA and PDT that takes QoL into account. The details will be provided in a Statistical Analysis Plan.
Overall survival (complementary perspective: median survival time)	through study completion, an average of 1 year	Estimates of the difference in median survival time between the groups will be based on the method of Chen and Zhang (PMID: 26983640).
Overall survival (complementary perspective: two-year overall survival)	up to two years	Kaplan-Meier estimates will be used.
Days alive and out of hospital up to two years	up to two years	This constitutes a basic and easy to understand measure of quality of life. Only in-hospital stays will be included in this endpoint and the day of arrival and dismissal will each be counted. The source of data will be the hospital records, epicrisis and patient disclosure.
Quality of Life (QoL) measured using QLQ-C30 at various points in time after randomization (V2 (14 days), V3 (ca. 3 months), as a function of time after 6 months, adjusting for the baseline value)	through study completion, an average of 1 year	Prolonging life is especially worthwhile if QoL is sufficiently good. The established cancer-specific Core Quality of Life questionnaire QLQ-C30 from the EORTC (European Organisation for Research will be used. Shortly after the index therapy (V2, V3), the difference between arms will be assessed. The requirement to stay indoors may affect QoL. At later points in time, a description per arm is of interest and will be based on a weighted mean of all available questionnaires, weighting according to calendar time.
Quality of Life (QoL) measured using FACT-Hep at various points in time after randomization (V2 (14 days), V3 (ca. 3 months), as a function of time after 6 months, adjusting for the baseline value)	through study completion, an average of 1 year	Prolonging life is especially worthwhile if QoL is sufficiently good. The Functional Assessment of Cancer Therapy - Hepatobiliary (FACT-Hep) questionnaire, containing the hepatobiliary-specific cancer subscale, will be used as a second instrument for assessing QoL. Shortly after the index therapy (V2, V3), the difference between arms will be assessed. The requirement to stay indoors may affect QoL. At later points in time, a description per arm is of interest and will be based on a weighted mean of all available questionnaires, weighting according to calendar time.
Laboratory parameter (haematocrit)	through study completion, an average of 1 year	Changes in laboratory parameters after index treatment (V3) and as a function of time will be analysed and compared between randomization arms.
Laboratory parameter (haemoglobin)	through study completion, an average of 1 year	Changes in laboratory parameters after index treatment (V3) and as a function of time will be analysed and compared between randomization arms.
Laboratory parameter (bilirubin)	through study completion, an average of 1 year	Changes in laboratory parameters after index treatment (V3) and as a function of time will be analysed and compared between randomization arms.
Laboratory parameter (albumin)	through study completion, an average of 1 year	Changes in laboratory parameters after index treatment (V3) and as a function of time will be analysed and compared between randomization arms.
Laboratory parameter (ALT)	through study completion, an average of 1 year	Changes in laboratory parameters after index treatment (V3) and as a function of time will be analysed and compared between randomization arms.
Laboratory parameter (leucocytes)	through study completion, an average of 1 year	Changes in laboratory parameters after index treatment (V3) and as a function of time will be analysed and compared between randomization arms.
Laboratory parameter (CA 19-9)	through study completion, an average of 1 year	Changes in laboratory parameters after index treatment (V3) and as a function of time will be analysed and compared between randomization arms.
Laboratory parameter (CRP)	through study completion, an average of 1 year	Changes in laboratory parameters after index treatment (V3) and as a function of time will be analysed and compared between randomization arms.
Pruritus as reported by patients on a scale from 0 ("no itching") to 10 ("worst imaginable itching").	through study completion, an average of 1 year	Pruritus will be analysed as a function of time.
Laboratory parameter (GGT)	through study completion, an average of 1 year	Changes in laboratory parameters after index treatment (V3) and as a function of time will be analysed and compared between randomization arms.

Trial Locations

Locations (20)

Uniklinik RWTH Aachen, Medizinische Klinik III; 🇩🇪 Aachen, Germany

Universitätsklinikum Augsburg; III. Med. Klinik; 🇩🇪 Augsburg, Germany

Vivantes Netzwerk für Gesundheit GmbH, Klinikum Friedrichshain, Innere Medizin/Gastroenterologie; 🇩🇪 Berlin, Germany

Universitatsklinikum Bonn, Medizinische Klinik und Poliklinik I; 🇩🇪 Bonn, Germany

Universitätsklinikum Frankfurt, Medizinische Klinik 1; 🇩🇪 Frankfurt, Germany

Universitätsklinikum Freiburg, Medizinische Klinik II, Abteilung Gastroenterologie, Hepatologie, Endokrinologie & lnfektiologie; 🇩🇪 Freiburg, Germany

Universitätsmedizin Greifswald Klinik für Innere Medizin A; 🇩🇪 Greifswald, Germany

Site: Martin-Luther-Universitat Halle-Wittenberg, Universitätsklinik und Poliklinik für Innere Medizin I; 🇩🇪 Halle, Germany

Klinikum Hanau; Klinik für Gastroenterologie, Diabetologie und Infektiologie; 🇩🇪 Hanau, Germany

KRH Klinikum Siloah, Klinik für Gastroenterologie; 🇩🇪 Hannover, Germany

Klinikum St. Georg gGmbH; Klinik für Gastroenterologie, Hepatologie, Diabetologie und Endokrinologie; 🇩🇪 Leipzig, Germany

University Hospital of Leipzig, Department of Gastroenterology; 🇩🇪 Leipzig, Germany

RKH Kliniken Ludwigsburg- Bietigheim gGmbH, Klinik für Innere Medizin, Gastroenterologie, Hämato-Onkologie, Diabetologie und Infektiologie; 🇩🇪 Ludwigsburg, Germany

Universitätsmedizin Mannheim, II. Medizinische Klinik; 🇩🇪 Mannheim, Germany

Universitätsklinikum Gießen und Marburg GmbH (UKGM); Klinik für Innere Medizin mit den Schwerpunkten Gastroenterologie, Endokrinologie, Stoffwechsel und klinische Infektiologie; 🇩🇪 Marburg, Germany

Klinikum der LMU München, Medizinische Klinik II, Campus Großhadern; 🇩🇪 München, Germany

Universitlitsklinikum Munster Medizinische Klinik B (Gastroenterologie, Hepatologie, Endokrinologie, Klinische lnfektiologie); 🇩🇪 Münster, Germany

Klinikum Nürnberg Nord; Gastroenterologie/ Endokrinologie; 🇩🇪 Nürnberg, Germany

Robert-Bosch-Krankenhaus (RBK) Stuttgart; Gastroenterologie, Hepatologie und Endokrinologie; 🇩🇪 Stuttgart, Germany

Universitätsklinikum Tübingen, Medizinische Klinik I; 🇩🇪 Tübingen, Germany