Clinical Trial Results:
Randomized, open-label, parallel-group, multi-centre phase II clinical trial with active cellular immunotherapy DCVAC/PCa in patients with castrate-resistant prostate cancer
Summary
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EudraCT number |
2011-004735-32 |
Trial protocol |
CZ |
Global end of trial date |
22 Feb 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
04 Mar 2018
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First version publication date |
04 Mar 2018
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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 |
SP001
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02105675 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Sotio a.s.
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Sponsor organisation address |
Jankovcova 1518/2, Prague, Czech Republic, 170 00
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Public contact |
Clinical Trials Sotio, SOTIO a.s., +420 224175111, clinicaltrial@sotio.com
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Scientific contact |
Clinical Trials Sotio, SOTIO a.s., +420 224175111, clinicaltrial@sotio.com
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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 Feb 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
22 Feb 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
22 Feb 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 |
The objectives of this clinical trial were to estimate the survival rate of patients 34 months after randomization; to estimate the proportion of patients without disease progression and without PSA progression 34 months after randomization; to evaluate quality of life and pain scale scoring using the standardized European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30, version 3; and to evaluate the incidence of AEs (with the exception of disease progression-related AEs).
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Protection of trial subjects |
Not applicable
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Background therapy |
Docetaxel 75 mg/m2 at 3-week intervals combined with prednisone 5 mg orally twice daily | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
24 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 |
Czech Republic: 62
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Worldwide total number of subjects |
62
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EEA total number of subjects |
62
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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 |
42
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 18 clinical study centers in the Czech Republic participated in the study, and 13 screened at least 1 patient onto the study. Recruitment period started on 24-Feb-2012 (first patient signed the informed consent form) and ended on 28-Feb-2014 (last patient signed the informed consent form). | |||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Screened: 87 Randomized: 62 Analyzed for efficacy: 47 Analyzed for safety: 47 | |||||||||||||||||||||||||||||||||
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 |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||||||||||||||
Blinding implementation details |
Not applicable
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Immunotherapy group | |||||||||||||||||||||||||||||||||
Arm description |
DCVAC/PCa in combination with chemotherapy; patients in the immunotherapy group were treated with 50 mg/day of oral cyclophosphamide for 7 days before the first dose of DCVAC/PCa and applied imiquimod cream to the planned DCVAC/PCa injection sites 24 hours before each DCVAC/PCa administration | |||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
DCVAC/PCa
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Investigational medicinal product code |
Not applicable
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Other name |
Not applicable
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Pharmaceutical forms |
Dispersion for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subcutaneous injection of approximately 1×10e7 autologous dendritic cells; oral cyclophosphamide 50 mg/day for 7 days before the first dose of DCVAC/PCa; imiquimod cream applied to the planned DCVAC/PCa injection sites 24 hours before each DCVAC/PCa administration
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Arm title
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Control group | |||||||||||||||||||||||||||||||||
Arm description |
Chemotherapy alone | |||||||||||||||||||||||||||||||||
Arm type |
No intervention | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
Immunotherapy group
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Reporting group description |
DCVAC/PCa in combination with chemotherapy; patients in the immunotherapy group were treated with 50 mg/day of oral cyclophosphamide for 7 days before the first dose of DCVAC/PCa and applied imiquimod cream to the planned DCVAC/PCa injection sites 24 hours before each DCVAC/PCa administration | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Control group
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Reporting group description |
Chemotherapy alone | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Immunotherapy group
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Reporting group description |
DCVAC/PCa in combination with chemotherapy; patients in the immunotherapy group were treated with 50 mg/day of oral cyclophosphamide for 7 days before the first dose of DCVAC/PCa and applied imiquimod cream to the planned DCVAC/PCa injection sites 24 hours before each DCVAC/PCa administration | ||
Reporting group title |
Control group
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Reporting group description |
Chemotherapy alone | ||
Subject analysis set title |
mITT
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
All randomized patients who started chemotherapy except those for whom no data were available following the randomization visit. It was not clinically meaningful to include patients who did not start chemotherapy as the information from these patients did not reflect the real effect of the study treatment. Therefore, the mITT population was the primary population when evaluating the study endpoints.
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Subject analysis set title |
Safety
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All randomized patients who received at least 1 dose of chemotherapy (control group) and, at the same time, received at least 1 dose of DCVAC/PCa (immunotherapy group)
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End point title |
Survival rate of patients 34 months after randomization | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
34 months after randomization
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Notes [1] - mITT [2] - mITT |
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Statistical analysis title |
Primary analysis | ||||||||||||
Statistical analysis description |
Kaplan-Meier analysis and log-rank test
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Comparison groups |
Control group v Immunotherapy group
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Number of subjects included in analysis |
47
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.2791 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
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End point title |
Survival rate of patients without disease progression and without PSA progression 34 months after randomization | ||||||||||||
End point description |
Disease progression was defined as at least 2 additional lesions on bone scintigraphy and/or a new finding in soft tissues as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1; PSA progression was defined as 2 consecutive increases by at least 2 ng/mL at least 2 weeks apart and by >25% above the nadir or baseline value. The main analysis used the start of chemotherapy as baseline.
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End point type |
Secondary
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End point timeframe |
34 months after randomization
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Notes [3] - mITT [4] - mITT |
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Statistical analysis title |
Secondary analysis | ||||||||||||
Statistical analysis description |
Kaplan-Meier analysis and log-rank test
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Comparison groups |
Immunotherapy group v Control group
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Number of subjects included in analysis |
47
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.3196 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
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End point title |
Survival rate of patients without disease progression 34 months after randomization | ||||||||||||
End point description |
Disease progression was defined as at least 2 additional lesions on bone scintigraphy and/or a new finding in soft tissues as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The main analysis used the start of chemotherapy as baseline.
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End point type |
Secondary
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End point timeframe |
34 months after randomization
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Notes [5] - mITT [6] - mITT |
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Statistical analysis title |
Secondary analysis | ||||||||||||
Statistical analysis description |
Kaplan-Meier analysis and log-rank test
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Comparison groups |
Immunotherapy group v Control group
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Number of subjects included in analysis |
47
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.1803 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
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End point title |
Quality of life (Global health status) as per the standardized EORTC QLQ-C30 version 3 questionnaire | ||||||||||||
End point description |
Mean profiles of scales and items of the EORTC QLQ-C30 version 3 questionnaire display for each visit the mean ±1.96× standard error of the mean and the number of patients who completed the questionnaire. These profiles showed that mean scores of all items of the EORTC QLQ-C30 version 3
questionnaire were comparable in both treatment groups.
A repeated measurement analysis was performed to investigate whether treatment, baseline score, time (i.e., visit), or interaction of treatment with time (visit) had an effect on the scores of the Global health status. The baseline score was the only factor having a statistically significant effect on the scores of the Global health status (p <0.0001).
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End point type |
Secondary
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End point timeframe |
34 months after randomization
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Notes [7] - mITT [8] - mITT |
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Statistical analysis title |
Secondary analysis | ||||||||||||
Statistical analysis description |
A repeated measurement analysis was performed using a marginal model with a robust covariance matrix. As a response variable, the scores for “on-treatment” visits with more than 10 patients with an available score in either treatment group were included. As explanatory variables, terms for treatment, baseline score, time (i.e., visit), and an interaction for treatment and time were included.
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Comparison groups |
Control group v Immunotherapy group
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Number of subjects included in analysis |
47
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.6349 [9] | ||||||||||||
Method |
Marginal model | ||||||||||||
Confidence interval |
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Notes [9] - Effect of treatment on the scores of Global health status |
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End point title |
Pain scale influence scoring as per the standardized EORTC QLQ-C30 version 3 questionnaire | ||||||||||||
End point description |
Mean profiles of scales and items of the EORTC QLQ-C30 version 3 questionnaire display for each visit the mean ±1.96× standard error of the mean and the number of patients who completed the questionnaire. These profiles showed that mean scores of all items of the EORTC QLQ-C30 version 3
questionnaire were comparable in both treatment groups.
A repeated measurement analysis was performed to investigate whether treatment, baseline score, time (i.e., visit), or interaction of treatment with time (visit) had an effect on the scores of the Pain scales. The baseline score and visit were the two factors having a statistically significant effect on the scores of the Pain scale (p = 0.0001 and p = 0.0140, respectively).
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End point type |
Secondary
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End point timeframe |
34 months after randomization
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Notes [10] - mITT [11] - mITT |
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Statistical analysis title |
Secondary analysis | ||||||||||||
Statistical analysis description |
A repeated measurement analysis was performed using a marginal model with a robust covariance matrix. As a response variable, the scores for “on-treatment” visits with more than 10 patients with an available score in either treatment group were included. As explanatory variables, terms for treatment, baseline score, time (i.e., visit), and an interaction for treatment and time were included.
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Comparison groups |
Immunotherapy group v Control group
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Number of subjects included in analysis |
47
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
= 0.6089 [12] | ||||||||||||
Method |
Marginal model | ||||||||||||
Confidence interval |
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Notes [12] - Effect of treatment on the scores of Pain scales |
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events, serious adverse events: from the first dose of treatment to 30 days after the last dose of DCVAC/PCa (immunotherapy group) or completion/discontinuation of chemotherapy (control group)
Deaths: from consent signature to trial termination
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Adverse event reporting additional description |
The tables include information on treatment-emergent adverse events, treatment-emergent serious adverse events, and all deaths. An event causally related to treatment was one which was assessed by investigators as causally related to DCVAC/PCa administration.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.0
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Reporting groups
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Reporting group title |
Immunotherapy group
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Reporting group description |
DCVAC/PCa in combination with chemotherapy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Control group
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Reporting group description |
Chemotherapy alone | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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14 Dec 2011 |
- European Pharminvent Services to be responsible for pharmacovigilance services
- Added specifications of the assessments of leukapheresis feasibility (vein access evaluation) prior to the procedure for patients in the immunotherapy group
- Specification for HIV tests added (CE-marked kits; accredited laboratory) |
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11 Jun 2012 |
- Prolongation of the time frame for leukapheresis and for leukapheresis feasibility assessment
- Clarification of cyclophosphamide dosing
- Clarification of ACI dosing
- Highlighted synchronization of visits for both groups of patients
- Modified exclusion criteria
- Updated SAE reporting
- Explanation added for not performing leukapheresis in the control group
- Reasons for early termination of patient participation in the trial added - inability to perform leukapheresis or failure to manufacture ACI
- ACI transport and application description updated
- Prolonged sampling time frame for Immunology and Immunomonitoring to 6 months
- Explanation added that missed ACI administration is not considered a reason for termination of patients’ participation in the trial |
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11 Aug 2014 |
- Detailed description of exploratory objectives, endpoints and analysis
- Clearly distinguishing IMP from stimulating medication
- Detailed description of laboratory testing performed, including samples for research
- Statistical analysis section updated
- Information about phase I/II clinical trials conducted by the University Hospital Motol updated per current knowledge
- Section on concomitant medication was updated
- Updated safety reporting sections
- New term introduction: End of the Treatment, End of Study, End of Study Examination visit, Follow-up and Survival Follow-up
- Updated trial duration
- Updated section Rationale for Prostate Cancer Immunotherapy
- Terminology harmonization |
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23 Jul 2015 |
- Updated safety reporting sections to capture transfer of safety monitoring responsibilities from the European PharmInvent Services transferred to SOTIO a.s. as of 03-Jan-2015
- Implementation of the Pregnancy Data Collection Form and minor wording updates in the pharmacovigilance section
- Wording for Exploratory Endpoints and Analysis was detailed |
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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 |