Clinical Trial Results:
Pharmacogenetic study in castration-resistant prostate cancer patients treated with abiraterone acetate
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Summary
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EudraCT number |
2012-005036-28 |
Trial protocol |
FR |
Global end of trial date |
06 Mar 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
24 Dec 2021
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First version publication date |
24 Dec 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 |
2012/41
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01858441 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Centre Antoine Lacassagne
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Sponsor organisation address |
33 av de Valombrose, Nice, France,
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Public contact |
LOVERA Christine, CENTRE ANTOINE LACASSAGNE, +33 492031618, christine.lovera@nice.unicancer.fr
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Scientific contact |
LOVERA Christine, CENTRE ANTOINE LACASSAGNE, +33 492031618, christine.lovera@nice.unicancer.fr
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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 |
30 Aug 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
06 Mar 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
06 Mar 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 |
The primary objective will be to investigate the relationships between candidate-gene polymorphisms specifically related to AA pharmacology: CYP17A1, SLCO2B1 and SLCO2B3 (13 single nucleotide polymorphisms) and the clinical efficacy of AA in terms of progression-free survival. Such relationships will take into account relevant histo-prognostic factors of metastatic CRPC cancers (clinical staging, pre-treatment PSA, Gleason score) and treatment compliance.
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Protection of trial subjects |
In order to ensure the protection of the rights, safety and well-being of trials subjects, this clinical trial was performed in accordance with the Protocol, the Public Health Code Article 1121-1 and following of the law n ° 2004-806 of the Public Health Code, its decrees and orders in force, Good Clinical Practice, 24 November 2006, the European Directive 2005/28/EC of 8 April 2005 and 2011/20/CE, the decision published in the OJ of 30/11/2006 laying down rules of good clinical practice for biomedical research relating to medicinal products for human and guide of good clinical practice (including guideline CT-1).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
15 Apr 2015
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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 |
France: 148
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Worldwide total number of subjects |
148
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EEA total number of subjects |
148
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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) |
20
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From 65 to 84 years |
120
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85 years and over |
8
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||
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Pre-assignment
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Screening details |
Patients who have had disease progression after failure of androgen deprivation therapy. Over 330 expected patients, 148 patients have been screened and included, including 2 patients wrongly included. | ||||||||||||||||||||||
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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 |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||
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Arms
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Arm title
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Patient with mCRPC | ||||||||||||||||||||||
Arm description |
- Abiraterone acetate 1000 mg (500 mg x 2 tablets) daily - Prednisone or prednisolone 10 mg daily, or any other corticotherapy based on the investigator’s choice and the standard of care of each center | ||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||
Investigational medicinal product name |
Abiraterone acetate
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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 |
Abiraterone acetate 1000 mg (500 mg x 2 tablets) daily
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Patient with mCRPC
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Reporting group description |
- Abiraterone acetate 1000 mg (500 mg x 2 tablets) daily - Prednisone or prednisolone 10 mg daily, or any other corticotherapy based on the investigator’s choice and the standard of care of each center | ||
Subject analysis set title |
study patient cohort
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Included patients with mCRPC
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End point title |
Radiologic survival-free progression | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Radiologic survival-free progression up to 36 months
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Statistical analysis title |
Primary analysis | ||||||||||||
Statistical analysis description |
Relationships between candidate-gene polymorphisms specifically related to AA pharmacology: CYP17A1, SLCO2B1 and SLCO2B3 (13 single nucleotide polymorphisms) and the clinical efficacy of AA in terms of radiographic progression-free survival. Such relationships will take into account relevant histo-prognostic factors of metastatic CRPC cancers (clinical staging, pre-treatment PSA, Gleason score).
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Comparison groups |
Patient with mCRPC v study patient cohort
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Number of subjects included in analysis |
204
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Analysis specification |
Pre-specified
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Analysis type |
other [1] | ||||||||||||
P-value |
= 5 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
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| Notes [1] - Relationships between polymorphisms and radiologic SFP |
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End point title |
biological survival-free progression | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
biological survival-free progression up to 36 months
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| No statistical analyses for this end point | |||||||||
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End point title |
global survival | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
global survival up to 36 months
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Adverse events information
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Timeframe for reporting adverse events |
Overall period of the study
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23
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Reporting groups
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Reporting group title |
Experimental arm
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 2% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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07 Aug 2013 |
- Addition of precautions for use in handling Zytiga
- Establishment of a serum library over the duration of the study in the context of hormonal assays |
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03 Mar 2014 |
- Modification of the protocol in view of recent developments and recommendations with regard to the therapeutic management of patients with metastatic hormone-resistant prostate cancer.
- Abiraterone Acetate (AA) has received Marketing Authorization for first-line metastatic administration.
- The Scientific Committee of the study therefore deemed it appropriate to no longer consider patients who received a first line of metastatic chemotherapy with Docetaxel, but patients indicated to receive AA in the first metastatic line. |
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18 Jun 2014 |
- Modification of the inclusion criteria
- Change of principal investigator at center 03 (Institut BERGONIE in BORDEAUX) following the departure of Dr Nadine HOUEDE
- Removal of center 06 (AP-HP - Saint Louis Hospital)
- Addition of 6 new research centers |
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28 Oct 2015 |
• Addition of a paragraph presenting the optional ancillary studies which have been added to the protocol:
o Study of mutations in the gene encoding the androgen receptor (AR) offered only to patients included outside CAL for reasons of the quantity of tubes collected.
o Feasibility study on AR-V7, a predictor of response to AA treatment. This study will only be carried out on consenting patients included in CAL (center 1) for reasons of logistical simplicity.
• In view of the rhythm of inclusions, the inclusion period and the total duration of the study were reviewed.
• Beyond 6 months of treatment, clinical examinations were spaced every 3 months. |
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06 Jan 2016 |
Declaration of new co-investigators |
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21 Nov 2018 |
Change of principal investigator in centers |
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05 Jun 2019 |
This modification is made following the request of the pharmaceutical sponsor who produces the study treatment (ZYTIGA®): From June 1, 2019, only the 500 mg tablet form will be available in pharmacies. The protocol as well as the study documents have been modified accordingly.
In addition, the protocol has been brought into regulatory compliance with the addition of the GDPR to the regulatory framework. An information letter was sent to the centers to inform the patients included in the study in November 2018. |
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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 reported | |||
