Clinical Trial Results:
A randomised control trial to study the side effect profile and to establish measures of efficacy using Photofrin or 5 aminolaevulinic acid (ALA) photodynamic therapy in the eradication of dysplasia in Barrett’s columnar lined oesophagus
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Summary
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EudraCT number |
2005-005528-15 |
Trial protocol |
GB |
Global end of trial date |
30 Apr 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
18 Oct 2019
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First version publication date |
18 Oct 2019
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Other versions |
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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 |
05/059
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
University College London
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Sponsor organisation address |
Gower Street, London, United Kingdom,
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Public contact |
Gower Street, London , United
Kingdom, WC1E 6BT, Joint Research Office, ctimps@ucl.ac.uk
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Scientific contact |
Gower Street, London , United
Kingdom, WC1E 6BT, Joint Research Office, ctimps@ucl.ac.uk
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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 |
29 Jul 2015
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Apr 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To determine whether PDT using ALA is more efficacious for the complete ablation of high grade dysplasia in Barrett’s oesophagus than Photofrin.
To establish which drug has a better side effect profile.
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Protection of trial subjects |
A routine chest X ray will be taken before and 24-48 hours after PDT. Pleural effusion have been noted post-PDT with the licensed and study medications.
Dysphagia is a recognised complication of photodynamic therapy sometimes resulting in admission to hospital for rehydration and possible oesophageal dilation.
Nausea and vomiting are relatively common post photodynamic therapy. This normal settles promptly and and does not prolong the patient’s length of stay.
Aspiration pneumonia has been noted after photodynamic therapy. The occurrence of pneumonias is expected in a small number patients and rarely results in prolonged length of stay.
Pigmented urine has been noted on the day following ALA administration. This is thought to be related to the metabolism of the medication via the haem-biosynthesis pathway and has not resulted in any long term problems. If this occurs these patients will be work-up in the usual way in consultation with the
urologists.
Liver function tests will be taken 1-2 days after treatment. If more than twice the upper limit of normal, they will continue to be taken every 1-2 days until bilirubin and ALT return to within twice the upper limit of normal or until discharge, whichever is earlier. Transient abnormalities in liver function tests have been reported with ALA photodynamic therapy. All have resolved spontaneously without long-term sequelae.
Hypotension has been noted with the oral administration of ALA. All patients are now rehydated prior to
drug administration and excluded from the study if taking depot psychotropic medications.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
01 Feb 2006
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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 |
United Kingdom: 64
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Worldwide total number of subjects |
64
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EEA total number of subjects |
64
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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) |
2
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From 65 to 84 years |
57
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85 years and over |
5
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Recruitment
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Recruitment details |
- | |||||||||
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Pre-assignment
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Screening details |
Of 128 patients that were screened for eligibility from 2006–2009, 79 patients were recruited to the study and from these, 64 underwent randomisation | |||||||||
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Period 1
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Period 1 title |
Trial 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 | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Study Arm | |||||||||
Arm description |
PDT with oral ALA administration (study arm) | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Aminolaevulinic Acid (ALA)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for oral solution
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Routes of administration |
Oral use
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Dosage and administration details |
Oral ALA PDT:
• Normal saline infusion 12 hours prior to administration of ALA only.
• Anti-emetic: Granisetron (30 minutes prior to ALA administration).
• Following ingestion of ALA, patients must minimise exposure to sunlight and avoid strong indoor lighting for 36 hours.
• Patients receive ALA (60 mg/kg body weight) in 50 ml of distilled water in 3 divided doses at 5 hours, 4 hours and 3 hours before therapy. Patients receive light treatment ideally at 5 hours (but in any case not more than 7 hours) after initial oral ALA ingestion via a diffuser fibre at 1132J/cm (or 200J/cm2 in an 18mm diameter balloon or bolster).
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Arm title
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Standard Treatment Control | |||||||||
Arm description |
PDT with IV Photofrin administration (standard treatment control) | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Photofrin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
IV Photofrin PDT (Standard treatment parameters):
• Drug is administered intravenously (2mg/kg) by a cannula placed in a large bore vein in the antecubital fossa 3 days before light treatment.
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End points reporting groups
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Reporting group title |
Study Arm
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Reporting group description |
PDT with oral ALA administration (study arm) | ||
Reporting group title |
Standard Treatment Control
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Reporting group description |
PDT with IV Photofrin administration (standard treatment control) | ||
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End point title |
Complete reversal of high-grade dysplasia (CR-HGD) at 1 year post-PDT [1] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
1 year follow-up
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Of the 64 patients randomised, 34 were photosensitised with ALA and 30 with Photofrin. CR-HGD was 16/34 (47 %) in the ALA group and 12/30 (40 %) in the Photofrin group (Fisher’s exact test00.62). A Kaplan– Meier analysis of probability of the remaining without dysplasia demonstrated no significant difference in dysplasia-free interval between the two groups (χ20 0.91, p00.34) |
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
From randomisation to end of follow-up period
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
ctcae | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4.0
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Reporting groups
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Reporting group title |
Randomised patients
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Reporting group description |
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| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Non-serious adverse events are not available to be added to this dataset. |
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
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. | |||
| None reported | |||
