Clinical Trial Results:
A multi-centre phase II study using Carboplatin AUC-10 for metastatic seminoma with IGCCCG good prognosis disease - therapy directed by initial metabolic response on PET-CT [CAR-PET]
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Summary
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EudraCT number |
2009-009882-33 |
Trial protocol |
GB |
Global end of trial date |
13 Oct 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Sep 2018
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First version publication date |
06 Sep 2018
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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 |
TE-2009-01
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02272816 | ||
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 Management Office (JRMO), 5 Walden Street, London, United Kingdom, E1 2EF
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Public contact |
Dr Jonathan Shamash, Centre for Experimental Cancer Medicine, QMUL, bci-carpet@qmul.ac.uk
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Scientific contact |
Dr Jonathan Shamash, Barts Health NHS Trust, Jonathan.Shamash@bartshealth.nhs.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 |
13 Oct 2017
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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 |
13 Oct 2017
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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 the safety, efficacy and toxicity of carboplatin AUC-10 in metastatic seminoma in a multi centre setting.
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Protection of trial subjects |
Participant safety was continuously monitored through reporting of adverse events and laboratory assessments. Requirements for platelets, white blood cells and neutrophil levels for treatment to proceed were specified in the protocol with guidance on management in the event that these parameters were below the required levels.
A Trial Steering Committee (TSC) convened periodically throughout the trial to review the conduct of the clinical trial to ensure continuing patient safety.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
13 Feb 2012
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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 |
United Kingdom: 48
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Worldwide total number of subjects |
48
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EEA total number of subjects |
48
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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) |
47
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From 65 to 84 years |
1
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients with metastatic chemotherapy and radiotherapy naïve seminoma who had International Germ Cell Cancer Collaborative Group (IGCCCG) good prognosis disease (i.e. no non-pulmonary visceral metastases) were recruited into the study at two centres in London, United Kingdom between Feb - 2012 and Apr - 2015. | ||||||
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Pre-assignment
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Screening details |
48 patients were screened for the study and all were found to be eligible and were recruited into the study. | ||||||
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Pre-assignment period milestones
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Number of subjects started |
48 | ||||||
Number of subjects completed |
48 | ||||||
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Period 1
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Period 1 title |
On study (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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Carboplatin AUC-10 | ||||||
Arm description |
Carboplatin AUC-10 according to the Calvert formula (10 x (GFR (ml/min) + 25) mg | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Carboplatin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Carboplatin AUC 10 according to the Calvert formula (10 x (GFR (ml/min) + 25) mg was given in 5% glucose over 1 hour every 21 days. A PET-CT scan was carried out on day 17-21 of the first cycle. The PET - CT scans were centrally reviewed. If the PET - CT scan showed a complete response (Deauville ≤3) the patient would stop treatment after 3 cycles. If the PET – CT showed persistent activity (Deauville >3), then patients went on to have 4 cycles in total
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Baseline characteristics reporting groups
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Reporting group title |
On study
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Carboplatin AUC-10
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Reporting group description |
Carboplatin AUC-10 according to the Calvert formula (10 x (GFR (ml/min) + 25) mg | ||
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End point title |
Progression Free Survival [1] | ||||||||||
End point description |
Number of subjects progression free at 2 years from registration.
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End point type |
Primary
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End point timeframe |
2 years from registration.
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| 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: It is not possible to enter statistical analysis as at least 2 comparison groups are required for this. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Metabolic Response Rate | ||||||||||
End point description |
Number of subjects achieving i) complete metabolic response (CR) and ii) partial metabolic response (PR) after 1 cycle of treatment.
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End point type |
Secondary
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End point timeframe |
21 days
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| No statistical analyses for this end point | |||||||||||
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End point title |
Overall Survival | ||||||||||
End point description |
Number of subjects alive at 2 years from registration.
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End point type |
Secondary
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End point timeframe |
2 years from registration.
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| No statistical analyses for this end point | |||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Start of treatment until 30 days after last dose.
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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 |
18.0
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Reporting groups
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Reporting group title |
Carboplatin AUC-10
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Reporting group description |
Carboplatin AUC-10 according to the Calvert formula (10 x (GFR (ml/min) + 25) mg | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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30 Apr 2012 |
- Inclusion criterion 2 amended to specify minimum required glomerular filtration rate of 25ml/min (value was missing).
- Inclusion criterion 5 amended to clarify that age range is inclusive of 18 and 75 years.
- Full Blood Count added on Cycle 1 Day 13-17 to check blood counts prior to proceeding to cycle 4 (previous version specified only cycle 2-4).
- CT scan within 28 days of completing treatment removed as not required. |
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29 May 2012 |
Change in Sponsor name from Barts and the London NHS Trust to Barts Health NHS Trust. |
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19 Dec 2012 |
- Removal of requirement for post - treatment PET - CT scan for patients who have complete remission after cycle 1.
- Allowable window included for Day 1 procedures on Cycles 2 – 4.
- Confirmation that dose banding is not permitted added.
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24 Oct 2013 |
- Change in requirements for recording concomitant medications. The IMP for this study was a licensed product, therefore it was not deemed necessary to record concomitant medications administered as supportive care.
- Clarification added for when to recalculate Carboplatin dose. The glomerular filtration rate determined by EDTA clearance was only assessed pretreatment. Therefore the dose only needed to be recalculated if serum Creatinine rose >20% above baseline. |
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12 Feb 2015 |
- Clarification of the process for sending images for central review.
- Amendments to the reporting timelines for the central review.
- Change in Sponsor's representative.
- Addition of urgent safety measure procedures.
- Update to the pregnancy reporting procedures.
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21 Sep 2015 |
- Exemption of requirement for baseline CT scan if PET-CT scan was done instead if clinician already suspected diagnosis to avoid unnecessary scans for trial subjects. |
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10 Oct 2017 |
- Reduction of the follow-up period from three years to two years. This decision was made as normally less than 10% of the total recurrences occur beyond 2 years and hence it has now become convention to quote 2 year progression-free survival in germ cell tumour (GCT) studies. This change does not affect the scope or validity of trial results, and was made after review by the Chief Investigator and trial statistician.
- The end of the study definition was changed from “the date the last patient has completed his final follow up visit” to “3 months after the date when the last patient has completed his final follow up visit”. This was to allow additional time for data collection, cleaning, and analysis.
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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 | |||
