Clinical Trial Results:
GAMEC-SHORT (S) & GAMEC-ANTHRACYCLINE (A) RISK-ADAPTED PROTOCOL FOR RELAPSED GERM CELL TUMOURS (GCT)
Summary
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EudraCT number |
2006-001963-52 |
Trial protocol |
GB |
Global end of trial date |
14 Jan 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
23 Mar 2019
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First version publication date |
23 Mar 2019
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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 |
GAMEC II
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Queen Mary University London
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Sponsor organisation address |
5 Walden Street, London, United Kingdom, E1 2EF
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Public contact |
CECM Trials Team, CECM Trials Team, Queen Mary University of London, bci-cecmmonitoring@qmul.ac.uk
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Scientific contact |
CECM Trials Team, CECM Trials Team, Queen Mary University of London, bci-cecmmonitoring@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 |
10 Jan 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
14 Jan 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
14 Jan 2014
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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 |
This study aimed to address two questions. The first was whether treatment for patients with no identifiable risk factors could be shortened to 6 weeks (GAMEC-S (short)) and whether patients with these risk factors (either raised LDH at relapse or > 35 years old) would benefit from the substitution epirubicin for etoposide (GAMEC-A (anthracycline)).
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Protection of trial subjects |
Not applicable
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
03 Jul 2006
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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: 36
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Worldwide total number of subjects |
36
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EEA total number of subjects |
36
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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) |
36
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Between 21/08/2006 and 06/01/2012, 36 patients with relapsed germ cell tumours were recruited. | |||||||||
Pre-assignment
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Screening details |
Patients who relapsed with germ cell tumours after failure of cisplatin based combination chemotherapy were eligible for study entry. Patients had to have evidence of relapse based on the presence of rising tumour markers and/or the development of radiological progression on CT. | |||||||||
Pre-assignment period milestones
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Number of subjects started |
36 | |||||||||
Number of subjects completed |
36 | |||||||||
Period 1
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Period 1 title |
GAMEC (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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GAMEC-A | |||||||||
Arm description |
Patients with either a raised LDH and/or were 35 years or older were allocated to therapy with GAMEC-A ( actinomycin-D 1mg/m2 day 1, methotrexate 8g/m2 ,cisplatin 50mg/m2, day 2 and 3 and 8, epirubicin 37.5mg/m2 days 1 and 2 followed by pegfilgrastim 6mg on day 3), treatment was given on weeks1, 3 ,6 , 8 and 10 . From week 6 onwards day 8 cisplatin was omitted. The dose of methotrexate was adjusted according to glomerular filtration rate as determined by an EDTA clearance as follows:> 120ml/min- 10g/m2, 100-119ml/min 8g/m2, 80-99ml/min 6g/m2, 60-79ml/min 4g/m2, 40-59ml/min 2g/m2, 25-39ml/min. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Pegfilgrastin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
6 mgs
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Investigational medicinal product name |
Actinomycin - D
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
1 mg/m2
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Investigational medicinal product name |
Methotrexate
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
8 g/m2
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Investigational medicinal product name |
Etoposide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
90 mg/m2
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Investigational medicinal product name |
Cisplatin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
50 mg/m2
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Investigational medicinal product name |
Epirubicin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
37.5 mg/m2
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Arm title
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GAMEC-S | |||||||||
Arm description |
Patients with neither risk factor were treated with GAMEC-S. In this protocol epirubicin was replaced by etoposide 90mg/m2 days 1, 2, 3 and 4. Treatment was stopped after 3 cycles (weeks 1, 3, and 6 only). Dose reductions and treatment administration have been described previously. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Etoposide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
90 mg/m2
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Baseline characteristics reporting groups
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Reporting group title |
GAMEC
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
GAMEC - S
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Subject analysis set type |
Sub-group analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Patients with neither risk factor were treated with GAMEC-S. In this protocol epirubicin was replaced by etoposide 90mg/m2 days 1, 2, 3 and 4. Treatment was stopped after 3 cycles (weeks 1, 3, and 6 only). Dose reductions and treatment administration have been described previously.
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Subject analysis set title |
GAMEC-A
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Subject analysis set type |
Sub-group analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Patients with either a raised LDH and/or 35 years or older were allocated to therapy with GAMEC-A ( actinomycin-D 1mg/m2 day 1, methotrexate 8g/m2 ,cisplatin 50mg/m2, day 2 and 3 and 8, epirubicin 37.5mg/m2 days 1 and 2 followed by pegfilgrastim 6mg on day 3), treatment was given on weeks1, 3 ,6 , 8 and 10 . From week 6 onwards day 8 cisplatin was omitted. The dose of methotrexate was adjusted according to glomerular filtration rate as determined by an EDTA clearance as follows:> 120ml/min- 10g/m2, 100-119ml/min 8g/m2, 80-99ml/min 6g/m2, 60-79ml/min 4g/m2, 40-59ml/min 2g/m2, 25-39ml/min.
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End points reporting groups
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Reporting group title |
GAMEC-A
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Reporting group description |
Patients with either a raised LDH and/or were 35 years or older were allocated to therapy with GAMEC-A ( actinomycin-D 1mg/m2 day 1, methotrexate 8g/m2 ,cisplatin 50mg/m2, day 2 and 3 and 8, epirubicin 37.5mg/m2 days 1 and 2 followed by pegfilgrastim 6mg on day 3), treatment was given on weeks1, 3 ,6 , 8 and 10 . From week 6 onwards day 8 cisplatin was omitted. The dose of methotrexate was adjusted according to glomerular filtration rate as determined by an EDTA clearance as follows:> 120ml/min- 10g/m2, 100-119ml/min 8g/m2, 80-99ml/min 6g/m2, 60-79ml/min 4g/m2, 40-59ml/min 2g/m2, 25-39ml/min. | ||
Reporting group title |
GAMEC-S
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Reporting group description |
Patients with neither risk factor were treated with GAMEC-S. In this protocol epirubicin was replaced by etoposide 90mg/m2 days 1, 2, 3 and 4. Treatment was stopped after 3 cycles (weeks 1, 3, and 6 only). Dose reductions and treatment administration have been described previously. | ||
Subject analysis set title |
GAMEC - S
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Patients with neither risk factor were treated with GAMEC-S. In this protocol epirubicin was replaced by etoposide 90mg/m2 days 1, 2, 3 and 4. Treatment was stopped after 3 cycles (weeks 1, 3, and 6 only). Dose reductions and treatment administration have been described previously.
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Subject analysis set title |
GAMEC-A
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Patients with either a raised LDH and/or 35 years or older were allocated to therapy with GAMEC-A ( actinomycin-D 1mg/m2 day 1, methotrexate 8g/m2 ,cisplatin 50mg/m2, day 2 and 3 and 8, epirubicin 37.5mg/m2 days 1 and 2 followed by pegfilgrastim 6mg on day 3), treatment was given on weeks1, 3 ,6 , 8 and 10 . From week 6 onwards day 8 cisplatin was omitted. The dose of methotrexate was adjusted according to glomerular filtration rate as determined by an EDTA clearance as follows:> 120ml/min- 10g/m2, 100-119ml/min 8g/m2, 80-99ml/min 6g/m2, 60-79ml/min 4g/m2, 40-59ml/min 2g/m2, 25-39ml/min.
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End point title |
PFS at 2 years | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
2 years
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Statistical analysis title |
PFS at 2 years | ||||||||||||
Statistical analysis description |
Progression free survival of GAMEC-A and GAMEC-S patients were compared using Kaplan Meier curves with log-rank tests.
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Comparison groups |
GAMEC - S v GAMEC-A
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Number of subjects included in analysis |
36
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.11 [1] | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
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Notes [1] - The log rank p-value is a comparison of the K-M curves of the entire study i.e. not at 2 years. |
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End point title |
Overall survival | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
At 3 years
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Attachments |
OS |
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No statistical analyses for this end point |
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End point title |
PFS median | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Until progression or death
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Attachments |
PFS |
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No statistical analyses for this end point |
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End point title |
Response | |||||||||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
overall
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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 |
From the start of study treatment to 30 days after the last dose.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
NCI | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
3
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Reporting groups
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Reporting group title |
GAMEC-S
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
GAMEC-A
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Reporting group description |
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Frequency threshold for reporting non-serious adverse events: 1% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 Oct 2008 |
Closed Arm GAMEC-A following a relapse rate of 80% in the first 16 patients, which remained unchanged from previous studies. The regimen offered no advantage in terms of toxicity.
Change in Sponsor to Queen Mary University of London |
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23 Dec 2008 |
Supplier change for the IMPs cisplatin and etoposide. |
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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 |