Clinical Trial Results:
A phase II single arm, multi-centre trial of triamcinolone with a GnRH analog for castration resistant prostate cancer
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Summary
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EudraCT number |
2010-022010-32 |
Trial protocol |
GB |
Global end of trial date |
24 Sep 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
09 Mar 2024
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First version publication date |
09 Mar 2024
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Other versions |
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Summary report(s) |
Summary of Outputs |
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 |
PR201005
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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 |
Barts Health NHS Trust
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Sponsor organisation address |
Joint Research and Management Office, 5 Walden Street, London, United Kingdom, E1 2EF
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Public contact |
Jonathan Shamash, Barts Health NHS Trust, +44 2034657108, jonathan.shamash2@nhs.net
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Scientific contact |
Jonathan Shamash, Barts Health NHS Trust, +44 2034657108, jonathan.shamash2@nhs.net
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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 |
22 Nov 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
24 Sep 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
24 Sep 2020
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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 examine whether triamcinolone (IM injection) offers an increased progression free survival (PFS) in patients with confirmed castration resistant prostate cancer (CRPC).
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Protection of trial subjects |
Following failure of ADT treatment, giving standard care dexamethasone, CRPC patients, have a resulting 50% response rate and an average of 4 months until progression. There remains a need to increase duration of response in this group of patients. The treatment of CRPC with triamcinolone is based on the understanding that CRPC is, in part, caused by mutational androgen receptor binding; using triamcinolone to suppress endogenous corticosteroids, results in a failure to stimulate those mutants with a promiscuous receptor which are able to proliferate through activation by adrenal steroids.
A formal interim analysis of the accumulated data was performed after the 35th patient in order to assess the effect of the trial IMP on the primary endpoint.
The purposes for the interim analysis were to:
o Assess the safety of the study treatment;
o Stop the trial early due to futility
If the results of the interim analysis indicated that there were 14 or less progression free survivors out of 35, the trial would be stopped.
Risk management
In the published study, treatment was well tolerated with no grade 3 or 4 toxicities were observed and the increased risk to hyperglycaemic patients was controlled by close monitoring of serum glucose and subsequent increases in anti diabetic medication.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Jun 2011
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Efficacy | ||
Long term follow-up duration |
12 Months | ||
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: 55
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Worldwide total number of subjects |
55
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EEA total number of subjects |
0
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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) |
8
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From 65 to 84 years |
44
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85 years and over |
3
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Recruitment
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Recruitment details |
A total of 63 evaluable patients with an interim analysis after recruitment of 35 patients were planned to be recruited to the study. However, end of recruitment was deemed to be when 29 patients survived progression free for 6 months. In total 55 evaluable patients were recruited between Jan 2012 and September 2020. | ||||||
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Pre-assignment
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Screening details |
55 evaluable patients were recruited to the study between 01 March 2012 and 03 October 2016. There were no screen failures. | ||||||
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Period 1
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Period 1 title |
Recruitment (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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Tiamcinolone and GnRH | ||||||
Arm description |
intra-muscular (IM) triamcinolone with a GnRH analog for castration resistant prostate cancer (CRPC). Patients will have a loading dose of 360mg on Cycle 1 Day 1. On cycle 2 Day 1, patients will receive a lower dose of 120mg of Triamcinolone. From cycle 3 onwards, patients’ dose will depend on their cortisol results. If patients’ blood cortisol is >30nmol/l, then their dose will be increased to 200mg otherwise their dose will remain at 120mg for that cycle and their cortisol tested again before the next cycle. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Triamcinolone
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Investigational medicinal product code |
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Other name |
Kenalog
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Pharmaceutical forms |
Solution for injection in vial
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Routes of administration |
Injection
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Dosage and administration details |
Patients were given a loading dose of 360mg on Cycle 1 Day 1 given by IM injection. On cycle 2 Day 1, patients received a lower dose of 120mg of Triamcinolone by injection. From cycle 3 onwards, patients’ dose was dependent on their cortisol results. If patients’ blood cortisol is >30nmol/l, then their dose was increased to 200mg otherwise their dose remained at 120mg for that cycle and their cortisol tested again before the next cycle.
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Baseline characteristics reporting groups
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Reporting group title |
Recruitment
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Tiamcinolone and GnRH
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Reporting group description |
intra-muscular (IM) triamcinolone with a GnRH analog for castration resistant prostate cancer (CRPC). Patients will have a loading dose of 360mg on Cycle 1 Day 1. On cycle 2 Day 1, patients will receive a lower dose of 120mg of Triamcinolone. From cycle 3 onwards, patients’ dose will depend on their cortisol results. If patients’ blood cortisol is >30nmol/l, then their dose will be increased to 200mg otherwise their dose will remain at 120mg for that cycle and their cortisol tested again before the next cycle. | ||
Subject analysis set title |
Evaluable Population
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Evaluable population is defined as all patients enrolled into the trial who completed at least 2 cycles of study medication and 12 weeks of follow-up.
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End point title |
Progression Free Survival at 6 months | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
6 months
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Statistical analysis title |
Progression Free Survival | ||||||||||||
Comparison groups |
Tiamcinolone and GnRH v Evaluable Population
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Number of subjects included in analysis |
95
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
Method |
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Parameter type |
Cox proportional hazard | ||||||||||||
Point estimate |
9.4
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Confidence interval |
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95% | ||||||||||||
sides |
2-sided
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lower limit |
7.4 | ||||||||||||
upper limit |
20.3 | ||||||||||||
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End point title |
Time to PSA Progression | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Time to prostate specific antigen progression from baseline
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Circulating Tumour Cells Response | ||||||||||||
End point description |
Baseline values presented only
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End point type |
Secondary
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End point timeframe |
Baseline to Cycle 1 Day 28
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Statistical analysis title |
Change between baseline and C1D28 | ||||||||||||
Comparison groups |
Tiamcinolone and GnRH v Evaluable Population
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Number of subjects included in analysis |
59
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||
P-value |
= 0.714 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
Baseline to end of treatment
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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 |
4.03
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Reporting groups
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Reporting group title |
Tiamcinolone and GnRH
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Reporting group description |
intra-muscular (IM) triamcinolone with a GnRH analog for castration resistant prostate cancer (CRPC). Patients will have a loading dose of 360mg on Cycle 1 Day 1. On cycle 2 Day 1, patients will receive a lower dose of 120mg of Triamcinolone. From cycle 3 onwards, patients’ dose will depend on their cortisol results. If patients’ blood cortisol is >30nmol/l, then their dose will be increased to 200mg otherwise their dose will remain at 120mg for that cycle and their cortisol tested again before the next cycle. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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27 Mar 2012 |
Volume of blood for CTC samples changed from 7.5ml to 15ml |
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19 Apr 2012 |
New patient information sheet explaining the patient’s exposure to radiation created. A separate PIS for sites where they do not consider bone scans as standard of care therefore requiring an ARSAC license and the other for sites where an ARSAC license is not necessary. |
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30 Apr 2012 |
Change of sponsor name from the Barts and the London NHS Trust to Barts Health NHS Trust. |
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04 Sep 2013 |
Updates to Interim analysis timelines, Target Accrual and TMG instead of TSC |
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11 Feb 2014 |
Increase of IMP dose from 120mg to 200mg if cortisol level ≥30nmol/l. |
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01 Dec 2015 |
Clarification that progression needs to be confirmed radiologically before a patient can be withdrawn. Information regarding PSA progression added. |
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27 Nov 2017 |
Updated end of trial definition |
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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. | |||
| None to report. | |||
