Clinical Trial Results:
GLiSten: Next generation intraoperative lymph node staging for stratified colon cancer surgery- Development Phase
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Summary
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EudraCT number |
2012-002623-15 |
Trial protocol |
IE GB |
Global end of trial date |
07 Aug 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
22 May 2020
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First version publication date |
22 May 2020
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Other versions |
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Summary report(s) |
GLiSten |
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 |
GS11/9681
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
University of Leeds
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Sponsor organisation address |
Worsley Building, Leeds, United Kingdom, LS2 9JT
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Public contact |
Catherine Lowe, Clinical Trials Research Unit, 0113 3431494, c.m.lowe@leeds.ac.uk
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Scientific contact |
Catherine Lowe, Clinical Trials Research Unit, 0113 3431494, c.m.lowe@leeds.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 |
07 Aug 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
07 Aug 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
07 Aug 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 optimise the dose of oral 5-ALA administration for intra-operative fluorescence diagnosis of metastatic lymph nodes in colon cancer.
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Protection of trial subjects |
Participants for this study will be selected on the basis that they have a diagnosis of colon cancer that requires surgical resection, and are suitable for segmental colectomy with D3 lymphadenectomy. There will be the normal risk of surgical complications associated with general anaesthesia and surgical resection. There is a small risk of photosensitivity reactions related to 5-ALA administration. This includes transient derangement of liver function tests (returning to baseline at 24 – 72 hours post-administration) and skin hypersensitivity reactions due to exposure to UV-light. Other mild and transient side effects associated with 5-ALA administration include nausea, vomiting, tachycardia, and hypotension. When 5-ALA is administered in conjunction with surgical resection of malignant brain tumours, a potential side effect is brain oedema. In response to these potential adverse effects, all patients will be kept out of direct sunlight for at least the first 48 hours following surgery and monitored for changes in vital signs and liver function (this is normal postoperative care). During the operation patient’s eyes and skin will be protected from the operating lights, using standard methods such as sterile drapes and tape to keep their eyes closed.
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Background therapy |
Colorectal cancer is the third most common cancer in the UK with an incidence of over 41,142 new cases per annum with over two thirds occurring in the colon (26,330 cases)(1); as such it represents a substantial burden on healthcare resources. In comparison to rectal cancer, which has seen improvement in survival over the past decade, the survival from colon cancer has remained largely unchanged with 5-year overall survival around 50%. In terms of segmental distribution, the right colon is the most common site harbouring ~25% of colorectal cancers, followed by the sigmoid colon with ~20%. Curative resection involves segmental colectomy to resect the primary cancer and the draining lymphatic field. Emerging evidence suggests that the standard of segmental colectomy as performed in the UK is of variable quality and that improvement in technique may help to improve survival outcomes with a survival advantage of up to 27% in patients with lymph node involvement (2). If this is correct, then a change in surgical technique to complete mesocolic resection and extended D3 lymphadenectomy would make a substantial contribution to improving the prognosis of patients with colon cancer (3-5). The corollary is that only ~25% of patients have lymph node involvement, meaning that in the other 75% of patients extended D3 lymphadenopathy potentially represents overtreatment. Such surgical changes can be quickly and cheaply introduced into practice and even very modest improvements in outcome, way below the potential that could be achieved, would be highly cost effective. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 May 2013
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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 |
United Kingdom: 37
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Country: Number of subjects enrolled |
Ireland: 7
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Worldwide total number of subjects |
44
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EEA total number of subjects |
44
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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) |
9
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From 65 to 84 years |
33
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85 years and over |
2
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Recruitment
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Recruitment details |
A total of 44 patients were recruited to the trial with no participants withdrawing during the study period. A total of 37 patients were recruited at St James’s University Hospital, Leeds, UK, and seven were recruited from The Mater Misericordiae University Hospital, Dublin, Ireland. | |||||||||
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Pre-assignment
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Screening details |
Patients will be identified via cancer multidisciplinary team meetings and approached in outpatient clinics for participation in the study. Patients will be approached during standard clinic visits for management of their disease and will be provided with verbal and written details about the trial. | |||||||||
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Period 1
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Period 1 title |
Main Trial Period (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Not applicable
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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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Cohort 1- 20mg/kg of 5-ALA | |||||||||
Arm description |
Cohort 1 patients were recruited between October 2013 and October 2014 and received an oral dose of 20 mg/kg of 5-ALA. Eighteen patients were required to achieve the target of 10 patients with metastatic LN disease as detected on standard histopathology. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
5-ALA 20mg/kg
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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 |
Cohort 1 patients received an oral dose of 20 mg/kg of 5-ALA.
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Arm title
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Cohort 2- 30mg/kg of 5-ALA | |||||||||
Arm description |
Cohort 2 patients were recruited between October 2014 and June 2015 and received an oral dose of 30 mg/kg of 5-ALA, in line with the dose escalation defined in the trial protocol. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
5-ALA 30mg/kg
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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 |
Cohort 2 patients received an oral dose of 30 mg/kg of 5-ALA.
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Baseline characteristics reporting groups
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Reporting group title |
Main Trial Period
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Cohort 1- 20mg/kg of 5-ALA
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Reporting group description |
Cohort 1 patients were recruited between October 2013 and October 2014 and received an oral dose of 20 mg/kg of 5-ALA. Eighteen patients were required to achieve the target of 10 patients with metastatic LN disease as detected on standard histopathology. | ||
Reporting group title |
Cohort 2- 30mg/kg of 5-ALA
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Reporting group description |
Cohort 2 patients were recruited between October 2014 and June 2015 and received an oral dose of 30 mg/kg of 5-ALA, in line with the dose escalation defined in the trial protocol. | ||
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End point title |
Patients with fluorescent LNs [1] | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
N
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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: Please see the attached results paper for all details regarding statistical analysis's performed. |
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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 |
Adverse events /reactions will be collected for all participants from the time of registration into the trial until 30 days post-operatively and will be evaluated for duration and intensity. Information will be recorded on the relevant CRF
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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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| Frequency threshold for reporting non-serious adverse events: 0% | |||
| 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: No Drug Related Serious Adverse events occured on the trial, only minor 5-ALA side effects. Details of all adverse events can be found in the attached publication. |
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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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22 May 2013 |
Changes made to the Protocol and PIS for the trial in light of comments from the MHRA and Irish Medicines Board. Protocol & PIS amended to v3.0. This amendment was approved by the REC on 29/4/2013, and by the MHRA on 22/5/2013 |
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19 Nov 2013 |
Amendment submitted to temporarily halt the trial, so the research team could work with the manufacturer to address the issue of non-fluorescence in the trial IMP. No patients were adversely affected by this failure of the IMP to fluoresce. |
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19 Dec 2013 |
This amendment was submitted to restart the trial following the previous temporary halt amendment. the trial was approved to restart by the MHRA on 6/2/2014 |
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14 Mar 2014 |
Protocol & PIS amended to bring it in line with the changes to the IB for the trial IMP, recommended by the EMA. minor changes also made to the protocol to change the definition of normal renal function within eligibility criteria. |
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23 Jul 2014 |
Amendment submitted in Ireland to add and remove Irish trial sites from the study, as the Irish Chief Investigator moved place of employment. This amendment was submitted alongside the changes requested by the EMA in the previous amendment listed. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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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. | |||||||
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