Clinical Trial Results:
Cancer Oesophagus Gefitinib(COG) - Phase III randomised, double-blind, placebo-controlled trial of gefitinib (Iressa®) versus placebo in oesophageal cancer progressing after chemotherapy.
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Summary
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EudraCT number |
2007-005391-13 |
Trial protocol |
GB |
Global end of trial date |
18 May 2012
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Results information
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Results version number |
v1(current) |
This version publication date |
17 Nov 2021
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First version publication date |
17 Nov 2021
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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 |
OCTO_005
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Additional study identifiers
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ISRCTN number |
ISRCTN29580179 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
University of Oxford
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Sponsor organisation address |
CTRG, Joint Research Office, 1st Floor, Boundary Brook House, Churchill Drive, Headington, Oxford, United Kingdom, OX3 7GB
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Public contact |
As Scientific contact, As Scientific contact, 0000 0000000000, CTRG@admin.ox.ac.uk
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Scientific contact |
Clinical Trials and Research Governance Team, University of Oxford, Sponsor office as above., 0000 0000000000, CTRG@admin.ox.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 |
23 Jul 2013
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
18 May 2012
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Global end of trial reached? |
Yes
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Global end of trial date |
18 May 2012
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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 assess whether gefitinib will improve overall survival in patients with oesophageal cancer when compared to a placebo.
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Protection of trial subjects |
Please see primary publication.
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Background therapy |
Please see primary publication. | ||
Evidence for comparator |
Please see primary publication. | ||
Actual start date of recruitment |
30 Mar 2009
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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: 449
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Worldwide total number of subjects |
449
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EEA total number of subjects |
449
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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) |
231
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From 65 to 84 years |
216
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85 years and over |
2
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Recruitment
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Recruitment details |
For this phase 3 randomised trial, patients were recruited from 48 UK centres. Please refer to primary publication for more information. | ||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
766 patients assessed for eligibility. 316 excluded: 185 did not meet inclusion criteria 131 declined to participate. Please refer to primary publication for more information. 450 Enrolled. 1 withdrew consent. (Final total 449) | ||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Baseline (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Carer | ||||||||||||||||||||||||||||||
Blinding implementation details |
Patients, clinicians, local site staff and trial office staff were all blinded to the treatment allocation. The trial statistician held the code break information in an off-site location. Six months after completion of recruitment the blind was broken for the patients remaining on trial medication and patients on the gefitinib arm were allowed to continue on gefitinib.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | ||||||||||||||||||||||||||||||
Arm description |
Please refer to primary publication. Allocated to Placebo (n=225) Received allocated intervention (n=219) Did not start treatment (n=6) Completed baseline PROs (n=214) | ||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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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 |
Matched placebo as two tablets taken orally per day
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Arm title
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Study Drug. | ||||||||||||||||||||||||||||||
Arm description |
Allocated to Gefitinib (n=224) Received allocated intervention (n=212) Did not start treatment (n=11) Completed baseline PROs (n=209) | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Gefitinib
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Investigational medicinal product code |
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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 |
Two 250 mg tablets taken orally per day.
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Please refer to primary publication. Allocated to Placebo (n=225) Received allocated intervention (n=219) Did not start treatment (n=6) Completed baseline PROs (n=214) | ||
Reporting group title |
Study Drug.
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Reporting group description |
Allocated to Gefitinib (n=224) Received allocated intervention (n=212) Did not start treatment (n=11) Completed baseline PROs (n=209) | ||
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End point title |
Overall survival (OS) | |||||||||
End point description |
The primary outcome was overall survival (OS) defined as time from randomization until death from any cause with censoring for patients still alive at the end of the study.
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End point type |
Primary
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End point timeframe |
The primary endpoint was overall survival (OS).
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Statistical analysis title |
Please see primary publication | |||||||||
Statistical analysis description |
The sample size of 450 was estimated to detect an improvement from 10% 1-year survival, as reported by previous phase 2 trials to 18% with a power of 82·5%, two-sided 5% significance allowing for a 10% loss to follow-up (hazard ratio [HR] 0·745, 389 events). A statistical analysis plan was finalised before masking was broken and analysis undertaken. All analyses were done in the intention-to-treat population.
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Comparison groups |
Placebo v Study Drug.
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Number of subjects included in analysis |
449
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Analysis specification |
Pre-specified
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Analysis type |
other [1] | |||||||||
P-value |
= 0.05 [2] | |||||||||
Method |
Regression, Cox | |||||||||
Parameter type |
Cox proportional hazard | |||||||||
Point estimate |
0.05
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
0.05 | |||||||||
upper limit |
0.95 | |||||||||
| Notes [1] - Sensitivity analyses of overall and progression-free survival were done in the per-protocol population, defined as all patients randomly assigned to treatment groups, excluding those who did not start treatment, or who had major protocol deviation (no previous treatment, treatment breaks of >14 days). An intention-to-treat analysis for survival used Kaplan-Meier survival curves and the log-rank test, with Cox proportional hazards modelling to estimate HRs and 95% CIs. [2] - Please see primary publication for details of the statistical analysis. |
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End point title |
Progression free survival (PFS) etc. | ||||||||||||
End point description |
Secondary outcome measures were progression free survival (PFS) defined as time from randomisation until radiological or clinical progression or death from any cause if progression was not previously reported with censoring for patients alive and progression free at the end of the study; safety measured by assessing adverse reactions and toxicities of grade 2-5 for skin toxicity and diarrhoea (known side effects of gefitinib) and grade 3-5 for all other toxicities, which were collected up to 30 days post treatment completion. The primary pre-specified PRO outcomes were global health status/quality of life (QLQ-C30), dysphagia, difficulty eating and odynophagia (all QLQ-OG25) at 4 weeks.
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End point type |
Secondary
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End point timeframe |
progression free survival (PFS) - see below.
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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 |
Please see primary publication for details.
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Adverse event reporting additional description |
Please see primary publication for details.
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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: Please see primary publication for details. |
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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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26 Sep 2008 |
CTA Initial Application |
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06 Feb 2009 |
Substantial Amendment Notification to add new PIs and sites |
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20 Feb 2009 |
Substantial Amendment to update protocol to v2.0_09Sep2008 |
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10 Mar 2009 |
Substantial amendment to update protocol to v3.0_16Feb2009 |
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15 Apr 2009 |
Substantial Amendment Notification to add new PIs and sites |
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20 May 2009 |
Substantial Amendment Notification to add new PIs and sites |
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22 Jun 2009 |
Substantial Amendment Notification to add new PIs and sites |
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27 Aug 2009 |
Substantial Amendment Notification to change PI at site |
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27 Oct 2009 |
Substantial Amendment Notification to change PI at site
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20 Nov 2009 |
Substantial Amendment Notification to change PI at site
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25 Jan 2010 |
Substantial Amendment Notification to add new PIs and sites and change PI at site
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08 Feb 2010 |
Substantial Amendment Notification to change PI at site
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12 Feb 2010 |
Substantial Amendment Notification to change PI at site
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07 Jun 2010 |
Substantial Amendment Notification to change PI at site
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05 Jul 2010 |
Substantial amendment to update protocol to v4.0_15Apr2010 |
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13 Sep 2010 |
Substantial amendment to update protocol to v5.0_06Aug2009 |
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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. | |||
| Please refer to the primary publication for more details. | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/24950987 |
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