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

Primary Purpose

Hilar Cholangiocarcinoma

Status
Recruiting
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
Photosensitizer
Radiofrequency ablation (RFA)
Sponsored by
University of Leipzig
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hilar Cholangiocarcinoma focused on measuring Hilar Cholangiocarcinoma, Radiofrequency ablation (RFA), Photodynamic therapy (PDT), Photosensitizer, Klatskin Tumor, Bile Duct Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Universitatsklinikum Bonn, Medizinische Klinik und Poliklinik IRecruiting
  • Universitätsklinikum Frankfurt, Medizinische Klinik 1
  • Universitätsklinikum Freiburg, Medizinische Klinik II, Abteilung Gastroenterologie, Hepatologie, Endokrinologie & lnfektiologie
  • Site: Martin-Luther-Universitat Halle-Wittenberg, Universitätsklinik und Poliklinik für Innere Medizin IRecruiting
  • University Hospital of Leipzig, Department of GastroenterologyRecruiting
  • RKH Kliniken Ludwigsburg- Bietigheim gGmbH, Klinik für Innere Medizin, Gastroenterologie, Hämato-Onkologie, Diabetologie und InfektiologieRecruiting
  • Universitätsmedizin Mannheim, II. Medizinische KlinikRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Photodynamic therapy (PDT)

Radiofrequency ablation (RFA)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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).
Overall survival (complementary perspective: two-year overall survival)
Kaplan-Meier estimates will be used.
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)
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
September 8, 2022
Last Updated
March 14, 2023
Sponsor
University of Leipzig
Collaborators
Zentrum für Klinische Studien Leipzig
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1. Study Identification

Unique Protocol Identification Number
NCT05551299
Brief Title
Treatment of Non-resectable Bile Duct Cancer With Radiofrequency Ablation or Photodynamic Therapy
Acronym
CARP
Official Title
Cholangiocarcinoma Treatment With Radiofrequency Ablation or Photodynamic Therapy: a Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 10, 2023 (Actual)
Primary Completion Date
April 2028 (Anticipated)
Study Completion Date
April 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Leipzig
Collaborators
Zentrum für Klinische Studien Leipzig

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hilar Cholangiocarcinoma
Keywords
Hilar Cholangiocarcinoma, Radiofrequency ablation (RFA), Photodynamic therapy (PDT), Photosensitizer, Klatskin Tumor, Bile Duct Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
258 (Anticipated)

8. Arms, Groups, and Interventions

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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Hilar cholangiocarcinoma (cytological or histological confirmation) Surgery is not planned Age ≥ 18 years Written informed consent Exclusion Criteria: Tumour not accessible endoscopically Known hypersensitivity to porphyrins or to any of the other ingredients of the photosensitizer chosen Leukopenia (< 2000/mm3) Thrombocytopenia (< 100,000 / mm³) Severe, uncorrected coagulopathy (at the discretion of the physician) Suspected erosion of major blood vessels, because of the risk of life-threatening mass haemorrhage exists Porphyria (clinician's assessment) or other light-exacerbated diseases Severely impaired liver and or kidney function (at the discretion of the physician) Bedridden for more than 50% of the time (similar to ECOG (Eastern Cooperative Oncology Group) grade 3) Planned surgical procedure within the next 30 days Concurrent eye disease that will require a slit lamp examination within the next 30 days Prior radiotherapy within the last four weeks Previous PDT or RFA Planned liver transplantation 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) Participation in other interventional trials Patients under legal supervision or guardianship Pregnant or nursing women
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Albrecht Hoffmeister, Prof.Dr.med.
Phone
+49-341-97-12240
Email
albrecht.hoffmeister@medizin.uni-leipzig.de
First Name & Middle Initial & Last Name or Official Title & Degree
Marcus Hollenbach, Dr. med.
Phone
+49-341-97-12362
Email
marcus.hollenbach@medizin.uni-leipzig.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Albrecht Hoffmeister, Prof.Dr.med.
Organizational Affiliation
Universitätsklinikum Leipzig; Bereich Gastroenterologie
Official's Role
Principal Investigator
Facility Information:
Facility Name
Universitatsklinikum Bonn, Medizinische Klinik und Poliklinik I
City
Bonn
ZIP/Postal Code
53127
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dominik Kaczmarek, Dr.
Phone
+49 228 287 -15263
Email
Dominik.Kaczmarek@ukbonn.de
Facility Name
Universitätsklinikum Frankfurt, Medizinische Klinik 1
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jörg Trojan, Prof. Dr.
Facility Name
Universitätsklinikum Freiburg, Medizinische Klinik II, Abteilung Gastroenterologie, Hepatologie, Endokrinologie & lnfektiologie
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Armin Küllmer, Dr.
Facility Name
Site: Martin-Luther-Universitat Halle-Wittenberg, Universitätsklinik und Poliklinik für Innere Medizin I
City
Halle
ZIP/Postal Code
06120
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jonas Rosendahl, Prof. Dr.
Phone
+49 345 557 2661
Email
jonas.rosendahl@uk-halle.de
Facility Name
University Hospital of Leipzig, Department of Gastroenterology
City
Leipzig
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Albrecht Hoffmeister, Prof. Dr.
Phone
++49 - 341 - 97 12240
Email
Albrecht.Hoffmeister@medizin.uni-leipzig.de
Facility Name
RKH Kliniken Ludwigsburg- Bietigheim gGmbH, Klinik für Innere Medizin, Gastroenterologie, Hämato-Onkologie, Diabetologie und Infektiologie
City
Ludwigsburg
ZIP/Postal Code
71640
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andreas Wannhoff, Dr.
Phone
+4971419967201
Email
andreas.wannhoff@rkh-kliniken.de
Facility Name
Universitätsmedizin Mannheim, II. Medizinische Klinik
City
Mannheim
ZIP/Postal Code
68167
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sebastian Belle, PD Dr.
Phone
+49 621 383-4642
Email
sebastian.belle@umm.de

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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