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

Hilar Cholangiocarcinoma Clinical Trial

— CARP  

Official title:

Cholangiocarcinoma Treatment With Radiofrequency Ablation or Photodynamic Therapy: a Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05551299
• Other study ID #: CARP
• Secondary ID: 2022-500107-50-0
• Status: Recruiting
• Phase: Phase 4
• Start date: February 10, 2023
• Est. completion date: April 2028

Study information

• Verified date: February 2024
• Source: University of Leipzig
• Contact: Albrecht Hoffmeister, Prof.Dr.med.
• Phone: +49-341-97-12240
• Email: albrecht.hoffmeister[@]medizin.uni-leipzig.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 258
• Est. completion date: April 2028
• Est. primary completion date: April 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cholangiocarcinoma
• Hilar Cholangiocarcinoma
• Klatskin Tumor

Intervention

Drug:
• Photosensitizer
A photosensitizer, which is absorbed preferentially by tumour cells, is administered 24 - 48 hours prior to PDT. Light of a particular wavelength is then applied during endoscopic retrograde cholangiopancreatography (ERCP) to kill primarily cancer cells locally within the stenosis. Immediately after PDT treatment, new stents are inserted into all treated segments if needed.

Procedure:
• Radiofrequency ablation (RFA)
RFA is also carried out as part of an ERCP. The RFA-probe is placed within the tumour stenosis and electrical current is applied. New stents are inserted into all treated segments if needed.

Locations

Country	Name	City	State
Germany	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

Sponsors (2)

Lead Sponsor	Collaborator
University of Leipzig	Zentrum für Klinische Studien Leipzig

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	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.	through study completion, an average of 1 year
Secondary	Overall survival (complementary perspective: median survival time)	Estimates of the difference in median survival time between the groups will be based on the method of Chen and Zhang (PMID: 26983640).	through study completion, an average of 1 year
Secondary	Overall survival (complementary perspective: two-year overall survival)	Kaplan-Meier estimates will be used.	up to two years
Secondary	Overall survival (complementary perspective: restricted mean survival on a time horizon of two-years)	Kaplan-Meier estimates will be used (see e.g. PMID: 15690989)	through study completion, an average of 1 year
Secondary	Days alive and out of hospital 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.	up to two years
Secondary	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)	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.	through study completion, an average of 1 year
Secondary	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)	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.	through study completion, an average of 1 year
Secondary	Quality-adjusted life years (QALYs)	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.	through study completion, an average of 1 year
Secondary	Stent patency based on clinician's assessment (e.g. cholangitis, cholestasis, ultrasound)	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.	through study completion, an average of 1 year
Secondary	Laboratory parameter (leucocytes)	Changes in laboratory parameters after index treatment (V3) and as a function of time will be analysed and compared between randomization arms.	through study completion, an average of 1 year
Secondary	Laboratory parameter (haematocrit)	Changes in laboratory parameters after index treatment (V3) and as a function of time will be analysed and compared between randomization arms.	through study completion, an average of 1 year
Secondary	Laboratory parameter (haemoglobin)	Changes in laboratory parameters after index treatment (V3) and as a function of time will be analysed and compared between randomization arms.	through study completion, an average of 1 year
Secondary	Laboratory parameter (bilirubin)	Changes in laboratory parameters after index treatment (V3) and as a function of time will be analysed and compared between randomization arms.	through study completion, an average of 1 year
Secondary	Laboratory parameter (albumin)	Changes in laboratory parameters after index treatment (V3) and as a function of time will be analysed and compared between randomization arms.	through study completion, an average of 1 year
Secondary	Laboratory parameter (CA 19-9)	Changes in laboratory parameters after index treatment (V3) and as a function of time will be analysed and compared between randomization arms.	through study completion, an average of 1 year
Secondary	Laboratory parameter (CRP)	Changes in laboratory parameters after index treatment (V3) and as a function of time will be analysed and compared between randomization arms.	through study completion, an average of 1 year
Secondary	Laboratory parameter (ALT)	Changes in laboratory parameters after index treatment (V3) and as a function of time will be analysed and compared between randomization arms.	through study completion, an average of 1 year
Secondary	Laboratory parameter (GGT)	Changes in laboratory parameters after index treatment (V3) and as a function of time will be analysed and compared between randomization arms.	through study completion, an average of 1 year
Secondary	Pruritus as reported by patients on a scale from 0 ("no itching") to 10 ("worst imaginable itching").	Pruritus will be analysed as a function of time.	through study completion, an average of 1 year