Clinical Trial Results:
A prospective randomized clinical trial on 90Yttrium trans-arterial radio-Embolization (Therasphere) vs. standard of care (sorafenib) for the treatment of advanced Hepatocellular carcinoma (HCC) with Portal Vein Thrombosis (PVT).
Summary
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EudraCT number |
2012-005375-14 |
Trial protocol |
BE GB ES |
Global end of trial date |
23 May 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
16 Mar 2018
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First version publication date |
16 Mar 2018
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
TS-104
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01887717 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Biocompatibles UK Ltd
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Sponsor organisation address |
Chapman House, Farnham Business Park Weydon Lane, Farnham Surrey, United Kingdom, GU9 8QL
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Public contact |
Chantal Laframboise, Biocompatibles UK Ltd, Chantal.Laframboise@btgplc.com
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Scientific contact |
Chantal Laframboise, Biocompatibles UK Ltd, Chantal.Laframboise@btgplc.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
23 May 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
23 May 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
23 May 2017
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
Assess TheraSphere's meaningful benefit in survival in comparison with the standard-of-care (sorafenib) in patients with good hepatic function and advanced hepatocellular carcinoma (HCC) associated with portal vein thrombosis (PVT).
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Protection of trial subjects |
This trial was conducted in compliance with International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines for conducting, recording, and reporting trials, as well as for archiving essential documents. No trial procedures were performed on trial participants until written consent had
been obtained from them. The informed consent form (ICF), protocol, and amendments for this trial were submitted to and approved by the Ethics committee.
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Background therapy |
- | ||
Evidence for comparator |
Patients randomized to the control group received standard-of-care sorafenib. | ||
Actual start date of recruitment |
27 Feb 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 1
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Country: Number of subjects enrolled |
United Kingdom: 1
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Country: Number of subjects enrolled |
Belgium: 1
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Country: Number of subjects enrolled |
Italy: 20
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Country: Number of subjects enrolled |
France: 3
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Country: Number of subjects enrolled |
United States: 5
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Worldwide total number of subjects |
31
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EEA total number of subjects |
26
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
14
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From 65 to 84 years |
17
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85 years and over |
0
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Recruitment
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Recruitment details |
Patient enrollment started on 27 Feb 2014 and was terminated prematurely on 31 Mar 2016 due to slow recruitment, after randomization of 36 patients. Patients were enrolled at 13 centers in 6 countries (USA, BE, ES, FR, UK and IT). Analyses of efficacy and safety were performed on the treated population of 31 patients. | |||||||||||||||||||||
Pre-assignment
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Screening details |
Patients enrolled in this study had been diagnosed with PVT associated with unresectable advanced HCC and were not eligible for any curative procedure. Screening evaluations completed 14 days prior to randomization. Upon meeting eligibility for study participation, patients were randomized 1:1 to the TheraSphere group or the control group. | |||||||||||||||||||||
Period 1
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Period 1 title |
overall study period (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||
Blinding implementation details |
This was an open label study.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Sorafenib | |||||||||||||||||||||
Arm description |
Patients received sorafenib orally 400 mg twice daily. Medically appropriate dose adjustments and drug holidays due to adverse events (AEs) and toxicity were allowed. | |||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||
Investigational medicinal product name |
sorafenib
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Investigational medicinal product code |
sorafenib
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Patients received twice daily 400 mg, i.e. a total dose of 800 mg.
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Arm title
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Therasphere | |||||||||||||||||||||
Arm description |
TheraSphere was administered through the hepatic artery. Patients received TheraSphere at a dose consistent with the approved product label to the treated lobe of the liver. The target dose was 120 Gy ± 10%. | |||||||||||||||||||||
Arm type |
Device | |||||||||||||||||||||
Investigational medicinal product name |
Therasphere
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Radionuclide generator, Suspension for injection
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Routes of administration |
Intrahepatic use
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Dosage and administration details |
The target dose was 120 Gy ± 10%.
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Baseline characteristics reporting groups
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Reporting group title |
overall study period
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Reporting group description |
36 patients were randomized to treatment with TheraSphere or standard-of-care sorafenib. Analyses of efficacy endpoints were performed on the Treated Population, which comprised 31 patients. Summaries of safety endpoints are provided on the Safety Population, which is identical to the Treated Population. Baseline characteristics are reported from the treated population only. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Sorafenib
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Reporting group description |
Patients received sorafenib orally 400 mg twice daily. Medically appropriate dose adjustments and drug holidays due to adverse events (AEs) and toxicity were allowed. | ||
Reporting group title |
Therasphere
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Reporting group description |
TheraSphere was administered through the hepatic artery. Patients received TheraSphere at a dose consistent with the approved product label to the treated lobe of the liver. The target dose was 120 Gy ± 10%. |
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End point title |
Overall survival (OS) | |||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Overall survival was calculated as the interval between the randomization date and the date of death for any cause, with censoring at the date of last contact for patients alive.
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Attachments |
Kaplan-Meier Plot OS (Treated Population) |
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Statistical analysis title |
Overall Survival Statistics | |||||||||||||||
Comparison groups |
Therasphere v Sorafenib
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Number of subjects included in analysis |
31
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Analysis specification |
Pre-specified
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Analysis type |
superiority [1] | |||||||||||||||
P-value |
= 0.8753 | |||||||||||||||
Method |
Logrank | |||||||||||||||
Parameter type |
Hazard ratio (HR) | |||||||||||||||
Point estimate |
0.93
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Confidence interval |
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level |
95% | |||||||||||||||
sides |
2-sided
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lower limit |
0.36 | |||||||||||||||
upper limit |
2.38 | |||||||||||||||
Notes [1] - A hazard ratio of <1 corresponds to a longer survival for the Therasphere group. |
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Adverse events information
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Timeframe for reporting adverse events |
Safety was assessed at all visits for enrolled patients throughout the duration of the study.
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Adverse event reporting additional description |
Safety was assessed using v 4.0 of the National Cancer Institute’s Common Terminology for Adverse Events (NCI: CTAE); CTCAE v. 4.0 standards.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
14.0
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Reporting groups
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Reporting group title |
Sorafenib
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Reporting group description |
Patients received sorafenib orally 400 mg twice daily. Medically appropriate dose adjustments and drug holidays due to adverse events (AEs) and toxicity were allowed. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Therasphere
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Reporting group description |
TheraSphere was administered through the hepatic artery. Patients received TheraSphere at a dose consistent with the approved product label to the treated lobe of the liver. The target dose was 120 Gy ± 10%. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0.05% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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13 Sep 2013 |
Protocol version 2.0: Change of sponsor. |
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08 Aug 2014 |
Protocol version 3.0:
- Change in the inclusion/exclusion criteria
- Change in the statistical analysis plan
- Change in number of patients planned to be included
- Change in duration of the study |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
On 23 May 2017, the Sponsor announced early termination of the study because fewer than half of the patients remained in follow-up and there was therefore little scientific value in continuing to collect data from the remaining patients in the study. |