Clinical Trial Results:
AN OPEN LABEL RANDOMISED PHASE II STUDY COMPARING AZD2014 VERSUS EVEROLIMUS IN PATIENTS WITH ADVANCED METASTATIC RENAL CANCER AND PROGRESSION ON VEGF TARGETED THERAPY
Summary
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EudraCT number |
2012-002874-30 |
Trial protocol |
GB |
Global end of trial date |
31 Jan 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Jul 2016
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First version publication date |
06 Jul 2016
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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 |
008424QM
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01793636 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Queen Mary University London
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Sponsor organisation address |
2-4 Walden Street, , London, United Kingdom, E12EF
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Public contact |
Marianne Tomsa, Centre for Experimental Cancer Medicine, Queen Mary University London, bci-zebra@qmul.ac.uk
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Scientific contact |
Thomas Powles, Centre for Experimental Cancer Medicine, Queen Mary University London, bci-zebra@qmul.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 |
31 Jan 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 |
31 Jan 2015
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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 |
The primary objective is to investigate if AZD2014 is associated with an improvement in progression free survival (PFS) compared to everolimus.
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Protection of trial subjects |
Side effects were closely monitored during and after the study. Patients were required to attend clinic weekly for the first four weeks and then every 4 weeks whilst they were on study medication where adverse events were recorded. The patient information sheet included details on expected adverse events for patients to look out for and also detailed that unexpected events may occur. The independent data monitoring committee for the trial was in place throughout to closely assess the side effects of the drugs on a regular basis and the trial results to make sure there were no excess risks to patients. On-site monitoring was performed throughout the study to provide real time review of source data to allow for early detection signals.
There were potential risks due to radiation, from additional scans that were carried out as part of this study. A medical physics expert and clinical radiology expert reviewed the associated risks and confirmed that they were within reasonable limits for this patient group.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
27 Feb 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: 49
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Worldwide total number of subjects |
49
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EEA total number of subjects |
49
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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) |
31
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From 65 to 84 years |
18
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85 years and over |
0
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Recruitment
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Recruitment details |
Starting in February 2013, patients were randomised (1:1) to AZD2014 or everolimus at 10 centres across the UK. Trial was stopped early in June 2014. | |||||||||
Pre-assignment
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Screening details |
Inclusion criteria included patients with advanced or metastatic ccRCC and progression of disease after exposure to at least 1 VEGF-targeted therapy. 67 patients were assessed for eligibility, however only 49 were randomised. 18 patients were excluded prior to randomised as their screening assessments showed they did not meet inclusion criteria. | |||||||||
Period 1
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Period 1 title |
Overall trial (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 |
NA
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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AZD2014 (50mg twice daily) | |||||||||
Arm description |
AZD2014 (50mg twice daily) | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
AZD2014
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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 |
50mg twice a day until disease progression.
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Arm title
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Everolimus (10mg once daily) | |||||||||
Arm description |
Everolimus (10mg once daily) | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Everolimus
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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 |
10mg once a day until disease progression.
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Baseline characteristics reporting groups
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Reporting group title |
AZD2014 (50mg twice daily)
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Reporting group description |
AZD2014 (50mg twice daily) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Everolimus (10mg once daily)
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Reporting group description |
Everolimus (10mg once daily) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
AZD2014 (50mg twice daily)
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Reporting group description |
AZD2014 (50mg twice daily) | ||
Reporting group title |
Everolimus (10mg once daily)
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Reporting group description |
Everolimus (10mg once daily) |
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End point title |
Progression-free survival | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
From randomisation until time of progression
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Attachments |
Kaplan-Meier Curve - PFS at Interim Analysi |
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Statistical analysis title |
Progression-free survival | ||||||||||||
Comparison groups |
Everolimus (10mg once daily) v AZD2014 (50mg twice daily)
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Number of subjects included in analysis |
49
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.01 | ||||||||||||
Method |
Stratified Log-rank | ||||||||||||
Parameter type |
Hazard ratio (HR) | ||||||||||||
Point estimate |
2.8
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Confidence interval |
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95% | ||||||||||||
sides |
2-sided
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lower limit |
1.2 | ||||||||||||
upper limit |
6.5 |
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Adverse events information
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Timeframe for reporting adverse events |
From informed consent to 30 days post last IMP
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4
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Reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
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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? Yes | |||||||
Date |
Amendment |
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28 Feb 2013 |
Change of Principal Investigators and addition of participating sites |
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14 Oct 2013 |
Expansion of details regarding risks of CT scans added to PIS/ICF |
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13 Feb 2014 |
Changes to Principal Investigators and addition of new sites only |
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31 Mar 2014 |
Administrative updates only. |
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23 Jun 2014 |
Notification of recruitment suspension following DMC review |
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10 Jul 2014 |
Notification of early recruitment termination (patients to remain on follow-up) |
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17 Dec 2014 |
Reduction of follow-up period |
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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. | |||||||
Small numbers precluded meaningful subset analysis, such as the importance of performance status or previous therapies with regard to outcome. | |||||||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/26364551 |