1. Overall survival (Time Frame - 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:
1. Overall survival (complementary perspective: median survival time) (Time Frame - 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).
2. Overall survival (complementary perspective: two-year overall survival) (Time Frame - up to two years): Kaplan-Meier estimates will be used.
3. Overall survival (complementary perspective: restricted mean survival on a time horizon of two-years) (Time Frame - through study completion, an average of 1 year): Kaplan-Meier estimates will be used (see e.g. PMID: 15690989)
4. Days alive and out of hospital up to two years (Time Frame - 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.
5. 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) (Time Frame - 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.
6. 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) (Time Frame - 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.
7. Quality-adjusted life years (QALYs) (Time Frame - 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.
8. Stent patency based on clinician's assessment (e.g. cholangitis, cholestasis, ultrasound) (Time Frame - 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.
9. Laboratory parameter (leucocytes) (Time Frame - 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.
10. Laboratory parameter (haematocrit) (Time Frame - 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.
11. Laboratory parameter (haemoglobin) (Time Frame - 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.
12. Laboratory parameter (bilirubin) (Time Frame - 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.
13. Laboratory parameter (albumin) (Time Frame - 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.
14. Laboratory parameter (CA 19-9) (Time Frame - 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.
15. Laboratory parameter (CRP) (Time Frame - 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.
16. Laboratory parameter (ALT) (Time Frame - 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.
17. Laboratory parameter (GGT) (Time Frame - 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.
18. Pruritus as reported by patients on a scale from 0 ("no itching") to 10 ("worst imaginable itching"). (Time Frame - through study completion, an average of 1 year): Pruritus will be analysed as a function of time.
Experimental: Photodynamic therapy (PDT) 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.
Experimental: 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.
Photosensitizer (Photodynamic therapy (PDT)): 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.
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.
Quelle: ClinicalTrials.gov
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"Treatment of Non-resectable Bile Duct Cancer With Radiofrequency Ablation or Photodynamic Therapy"
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