Clinical Trial Results:
A prospective, multi-centre, open label, non-randomised two stage phase II clinical trial evaluating the efficacy of abiraterone in patients with epithelial ovarian (including fallopian tube and primary peritoneal) cancer.
|
Summary
|
|
EudraCT number |
2013-000293-29 |
Trial protocol |
GB |
Global end of trial date |
28 Jan 2021
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
06 Feb 2022
|
First version publication date |
06 Feb 2022
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
ICR-CTSU/2012/10038
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
ISRCTN63407050 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Sponsor Identification Number:: CCR3948, ICR-CTSU Protocol Number: ICR-CTSU/2021/10038, CRUK Reference Number:: A16037, Main REC Reference:: 13/LO/1599, MHRA CTA Reference Number:: 15983/0242/001-0001 | ||
|
Sponsors
|
|||
Sponsor organisation name |
The Institute of Cancer Research
|
||
Sponsor organisation address |
5 Cotswold Road, Sutton, United Kingdom, SM2 5NG
|
||
Public contact |
Christy Toms, Clinical Trials Programme Manager, The Institute of Cancer Research, +44 0208 722 4266, coral-icrctsu@icr.ac.uk
|
||
Scientific contact |
Christy Toms, Clinical Trials Programme Manager, The Institute of Cancer Research, +44 0208 722 4266, coral-icrctsu@icr.ac.uk
|
||
Sponsor organisation name |
The Royal Marsden NHS Foundation Trust
|
||
Sponsor organisation address |
Downs Road, Sutton, United Kingdom,
|
||
Public contact |
Christy Toms, Clinical Trials Programme Manager, The Royal Marsden NHS Foundation Trust, +44 0208 722 4266, coral-icrctsu@icr.ac.uk
|
||
Scientific contact |
Christy Toms, Clinical Trials Programme Manager, The Royal Marsden NHS Foundation Trust, +44 0208 722 4266, coral-icrctsu@icr.ac.uk
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
22 Feb 2021
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
28 Jan 2021
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
28 Jan 2021
|
||
Was the trial ended prematurely? |
Yes
|
||
|
General information about the trial
|
|||
Main objective of the trial |
The primary objective of this study is to determine whether abiraterone has clinical activity (objective response rate assessed by imaging and/or CA125 tumour marker changes in the blood) in patients with epithelial ovarian cancer (EOC) that has relapsed within 12 months of last treatment.
26 patients 'unselected' for androgen receptor (AR) status will be treated in stage one and, if successful, a further 21 patients in stage two bringing the total number of patients required to 47.
|
||
Protection of trial subjects |
Patients were provided with full verbal and written informed consent regarding the purpose and procedures of the trial and the possible risks involved. A patient information sheet and consent form were provided and patients were given sufficient time to consider their participation. The Principal Investigator at each site was responsible for ensuring written informed consent was obtained for each patient.
Full details of the trial medication and its safety profile were provided in the patient information sheet. Patients had the opportunity to discuss any concerns they had in relation to this with their study team at site.
|
||
Background therapy |
All patients received prednisone or prednisolone (at clinician's discretion) at 5mg orally once daily to prevent secondary mineralocorticoid excess. | ||
Evidence for comparator |
This was a two-stage phase II, non-randomised clinical trial with all patients receiving abiraterone once a day on a continuous 28-day cycle until disease progression. | ||
Actual start date of recruitment |
09 Dec 2013
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
United Kingdom: 42
|
||
Worldwide total number of subjects |
42
|
||
EEA total number of subjects |
0
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
20
|
||
From 65 to 84 years |
21
|
||
85 years and over |
1
|
||
|
|||||||||||||||
|
Recruitment
|
|||||||||||||||
Recruitment details |
Forty-two patients were recruited from four UK centres between21 March 2014 and 3 November 2015 | ||||||||||||||
|
Pre-assignment
|
|||||||||||||||
Screening details |
Post-menopausal women with histologically or cytologically confirmed epithelial ovarian, fallopian tube (FT) or primary peritoneal (PP) cancer were eligible if they had progressed (radiological or CA125 criteria) within 12 months of last systemic anti-cancer therapy. 50 patients were registered, 42 proceeded to trial entry. | ||||||||||||||
|
Period 1
|
|||||||||||||||
Period 1 title |
Overall Trial (overall period)
|
||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Not applicable
|
||||||||||||||
Blinding used |
Not blinded | ||||||||||||||
|
Arms
|
|||||||||||||||
|
Arm title
|
Abiraterone | ||||||||||||||
Arm description |
All patients receive an oral dose of abiraterone 100mg (4 x 250mg tablets) once a day on a continuous 28 day cycle | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
abiraterone
|
||||||||||||||
Investigational medicinal product code |
|||||||||||||||
Other name |
|||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||
Dosage and administration details |
Oral dose of 1000mg (4 x 250mg) once a day on a continuous 28 day cycle
|
||||||||||||||
|
|||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Overall Trial
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Abiraterone
|
||
Reporting group description |
All patients receive an oral dose of abiraterone 100mg (4 x 250mg tablets) once a day on a continuous 28 day cycle | ||
Subject analysis set title |
Stage 1
|
||
Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Stage 1 includes the first 26 patients recruited to the CORAL trial regardless of evaluability of the patient.
|
||
Subject analysis set title |
Evaluable
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Any patient who had a scan at 12 weeks and/or progressed/died prior to 12 weeks is considered evaluable and will be included in the analysis of the evaluable population. Any patient discontinuing the trial for other reasons prior to 12 weeks would not be considered evaluable.
|
||
|
|||||||||||||||||||||
End point title |
Objective response [1] | ||||||||||||||||||||
End point description |
Primary endpoint is objective response rate at 12 weeks after registration. Objective response is defined as a complete or partial response according to joint RECIST/GCIG criteria.
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Up to 12 weeks from trial entry.
|
||||||||||||||||||||
| 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: This is a single arm study and no comparative analysis was performed, however the system expects at least 2 groups to be identified. All methods and options specified in the analysis section apply to statistical methods and summary measures to report and compare at least 2 independent groups, which is not the case in this single arm trial. There is no way of reporting one group inference and summary values without triggering an error or reporting inaccurate information. |
|||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Objective response according to RECIST | ||||||||||||||||||||||||
End point description |
The proportion of patients with objective response according to RECIST v1.1.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Up to 12 weeks after trial entry.
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| Notes [2] - 3 patients were considered evaluable for CA125 but non evaluable for RECIST. |
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Objective response according to GCIG (CA125) | ||||||||||||||||||||||||
End point description |
The proportion of patients with objective response according to CA125 criteria as recommended by the Gynaecologic Cancer InterGroup (GCIG) guidelines issued November 2005.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Up to 12 weeks post trial entry.
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| Notes [3] - 5 patients were evaluable for RECIST but not CA125 so are excluded from this analysis |
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Clinical benefit rate | ||||||||||||||||||||
End point description |
Clinical benefit rate according to RECIST/GCIG criteria at 12 weeks.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
Up to 12 weeks post trial entry.
|
||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||
End point title |
Progression free survival | ||||||||
End point description |
Progression free survival will be measured from date of registration until date of confirmed progressive disease or death. Subjects who have not progressed or died at time of analysis will be censored at the date of last follow up.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From trial entry until patient progression.
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Time to progression | ||||||||
End point description |
Time to progression is measured from date of registration until date of confirmed progressive disease. Subjects who have died without prior confirmation of progression or are alive and have not progressed will be considered censored at date of death/latest follow up.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From trial entry until progression.
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Overall survival | ||||||||
End point description |
Overall survival is measured from the date of registration until date of death of any cause.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From trial entry until death.
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From trial entry until 28 days post treatment discontinuation.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
14
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Abiraterone
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
All patients receive an oral dose of abiraterone 100mg (4 x 250mg tablets) once a day on a continuous 28 day cycle | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||
Substantial protocol amendments (globally) |
|||||||
| Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
||||||
11 Sep 2015 |
1. Update to Investigator Brochure v11 (22/09/2015) and associated protocol/patient information sheet changes
2. Change of principal analysis population to 'Intention to Treat' from the 'evaluable' population
3. Update to exclusion criterion 'unresolved bowel obstruction' to include 'or symptoms of sub-acute bowel obstruction'
4. Addition of exclusion criterion 'Ascites on clinical examination or significant ascites present on baseline imaging'
5. Addition of radiological confirmation of response (CT scan/MRI) at 28 days following initial assessment of response
6. Addition of a liver function test at the mid-point in cycle 1 to monitor serum transaminase levels following the first 2 weeks of abiraterone treatment.
7. Change in timing of optional progression sample collection from 'within 7 days after last treatment' to 'after last dose of abiraterone and before commencement of any new systemic therapy'
8. Change of AR positivity cut-off from 1% to 10% |
||||||
07 Oct 2015 |
1. Temporary halt to recruitment |
||||||
20 Feb 2017 |
1. Update to Investigator Brochure v12 (August 2015) |
||||||
Interruptions (globally) |
|||||||
| Were there any global interruptions to the trial? Yes | |||||||
|
|||||||
Limitations and caveats |
|||||||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
| None reported | |||||||
Online references |
|||||||
| http://www.ncbi.nlm.nih.gov/pubmed/33854564 |
|||||||
