Clinical Trial Results:
An open Phase I/II study of immunization with the recMAGE-A3 + AS15 Antigen Specific Cancer Immunotherapeutic in association with dacarbazine in patients with MAGE-A3 positive unresectable and progressive metastatic cutaneous melanoma
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Summary
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EudraCT number |
2008-001918-25 |
Trial protocol |
FR BE |
Global end of trial date |
17 Nov 2014
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Results information
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Results version number |
v2(current) |
This version publication date |
07 Apr 2021
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First version publication date |
13 Feb 2016
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Other versions |
v1 |
Version creation reason |
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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 |
111714
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
GlaxoSmithKline Biologicals
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Sponsor organisation address |
Rue de l’Institut 89, Rixensart, Belgium, B-1330
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Public contact |
Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com
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Scientific contact |
Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.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 |
12 May 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
17 Nov 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
17 Nov 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 |
Co-primary objectives of this study were to characterize in the overall population and in the gene signature (GS) subsets:
- The safety of MAGE-A3 ASCI study product in association with dacarbazine in patients with MAGE-A3-positive metastatic cutaneous melanoma, with emphasis on any possible toxic effects.
- The specific humoral and cellular immune response induced by the MAGE-A3 ASCI study product in association with dacarbazine in patients with MAGE-A3-positive metastatic cutaneous melanoma.
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Protection of trial subjects |
The patients will be observed closely for at least 30 minutes following the administration of treatments, with appropriate medical treatment readily available in case of a rare anaphylactic reaction.
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Background therapy |
- | ||
Evidence for comparator |
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Actual start date of recruitment |
26 May 2009
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Belgium: 10
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Country: Number of subjects enrolled |
France: 38
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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 |
- | ||||||||||||||||
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Pre-assignment
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Screening details |
During the screening the following steps occurred: check for inclusion/exclusion criteria, contraindications/precautions, medical history of the patients and signing informed consent forms. | ||||||||||||||||
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Period 1
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Period 1 title |
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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MAGE-A3 Group | ||||||||||||||||
Arm description |
Patients planned to receive intramuscularly up to 24 doses of MAGE-A3 ASCI (the study product), in 4 cycles | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
Other name
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Investigational medicinal product code |
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Other name |
recMAGE-A3 recombinant protein + immunological Adjuvant System, GSK2132231A
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Pharmaceutical forms |
Powder and solvent for suspension for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
Administration as follows: 12 administrations in Cycle 1, at 3-week intervals (Weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31 and 34) and 8 doses of a standard intravenous chemotherapy regimen consisting of dacarbazine and prophylactic anti-emetic medications administered over one hour on Weeks 1, 4, 7, 10, 13, 16, 19 and 22; 4 administrations in Cycle 2, at 6-week intervals (Weeks 38, 44, 50 and 56); 4 administrations in Cycle 3 at 3-month intervals and 4 administrations i at 6-month intervals.
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Investigational medicinal product name |
Darcabazine
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Investigational medicinal product code |
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Other name |
Chemotherapy
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
During Cycle 1, 8 doses of a standard intravenous chemotherapy regimen consisting of dacarbazine administered over one hour on Weeks 1, 4, 7, 10, 13, 16, 19 and 22;
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Investigational medicinal product name |
Anti-emetic medication
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Investigational medicinal product code |
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Other name |
A serotonin 5-HT3 receptor antagonist (e.g. ondansetron, dolasetron or granisetron)
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
Administration prior to each course of chemotherapy, according to standard procedures at the site.
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Investigational medicinal product name |
Anti-emetic medication
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Investigational medicinal product code |
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Other name |
A serotonin 5-HT3 receptor antagonist (e.g. ondansetron, dolasetron or granisetron)
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Pharmaceutical forms |
Pillules
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Routes of administration |
Oral use
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Dosage and administration details |
Administration at 6 hours after each course of chemotherapy, according to standard procedures at the site.
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Baseline characteristics reporting groups
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Reporting group title |
MAGE-A3 Group
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Reporting group description |
Patients planned to receive intramuscularly up to 24 doses of MAGE-A3 ASCI (the study product), in 4 cycles | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
GS+ Group
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Subset of patients with the pre-specified gene signature, receiving the MAGE-A3 ASCI product. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening.
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Subject analysis set title |
GS- Group
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Subset of patients without the pre-specified gene signature, receiving the MAGE-A3 ASCI product. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening.
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Subject analysis set title |
Unknown GS Group
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Subset of patients with unknown status as regards GS signature, receiving the MAGE-A3 ASCI product. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening.
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End points reporting groups
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Reporting group title |
MAGE-A3 Group
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Reporting group description |
Patients planned to receive intramuscularly up to 24 doses of MAGE-A3 ASCI (the study product), in 4 cycles | ||
Subject analysis set title |
GS+ Group
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subset of patients with the pre-specified gene signature, receiving the MAGE-A3 ASCI product. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening.
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Subject analysis set title |
GS- Group
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subset of patients without the pre-specified gene signature, receiving the MAGE-A3 ASCI product. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening.
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Subject analysis set title |
Unknown GS Group
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subset of patients with unknown status as regards GS signature, receiving the MAGE-A3 ASCI product. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening.
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End point title |
Number of patients reported with unsolicited adverse events (AEs) that were causally related to treatment administration by maximum grade. [1] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The assessed AEs were ASCI-related grade 3/4 adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. An unsolicited AE covers any untoward medical occurrence in a clinical investigation patient temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Related = AE assessed by the investigator as related to the treatment.
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End point type |
Primary
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End point timeframe |
Within the 31-day (Days 0-30) post-administration period.
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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: The scope of this primary endpoint was descriptive, no statistical analyses were conducted. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of patients reported with serious adverse events (SAEs) [2] | ||||||||
End point description |
Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Events which were part of the natural course of the disease under study (i.e., disease progression, recurrence) were captured as part of the clinical activity outcome variables in this study; therefore these did not need to be reported as SAEs. Progression/recurrence of the tumor in a patient was recorded as part of the clinical assessment data collection, and deaths due to progressive disease was recorded on a specific form, but not as an SAE. However, if the investigator considered that there was a causal relationship between treatment or protocol design/procedures and the disease progression/recurrence, then the event was reported as an SAE. Any new primary cancer (non-related to the cancer under study) was reported as an SAE.
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End point type |
Primary
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End point timeframe |
During the entire study period, up to 5 years
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| Notes [2] - 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: The scope of this primary endpoint was descriptive, no statistical analyses were conducted. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of seroconverted patients for anti-MAGE-A3 [3] | ||||||||||||||||||||
End point description |
Seroconversion was defined as a concentration of antibodies assessed that was greater than the cut-off value for a patient whose concentration of such antibodies was below the cut-off level before the initiation of treatment. Seroconverted patients were those patients with anti-MAGE-A3 antibody concentrations ≥ 27EL.U/mL.
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End point type |
Primary
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End point timeframe |
Post Dose 4 at Week 13 (W13).
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| Notes [3] - 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: The scope of this primary endpoint was descriptive, no statistical analyses were conducted. |
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Anti-MAGE-A3 antibody concentrations [4] | ||||||||||||||||||||
End point description |
Anti-MAGE-A3 antibody concentrations were presented ad geometric mean concentrations (GMTs) and expressed in ELISA units per millilitre (EL.U/mL)
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End point type |
Primary
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End point timeframe |
Post Dose 4 at Week 13 (W13).
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| Notes [4] - 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: The scope of this primary endpoint was descriptive, no statistical analyses were conducted. |
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Number of patients with treatment response for anti-MAGE-A3 antibodies [5] | ||||||||||||||||||||
End point description |
Treatment response defined as:
For initially seronegative patients: post-administration antibody concentration ≥ 27 EL.U/mL
For initially seropositive patients: post-administration antibody concentration ≥ 2 fold the pre-vaccination antibody concentration
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End point type |
Primary
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End point timeframe |
Post Dose 4 at Week 13 (W13).
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| Notes [5] - 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: The scope of this primary endpoint was descriptive, no statistical analyses were conducted. |
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Anti-MAGE-A3 antibody concentrations (CMI) [6] | ||||||||||||||||||||
End point description |
Analysis of MAGE-A3 cellular response was not performed as data were not collected.
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End point type |
Primary
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End point timeframe |
Post Dose 4 at Week 13 (W13).
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| Notes [6] - 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: The scope of this primary endpoint was descriptive, no statistical analyses were conducted. |
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| Notes [7] - No data collected [8] - No data collected [9] - No data collected [10] - No data collected |
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Concentrations of antibodies against protein D (Anti-PD) [11] | |||||||||||||||||||||||||
End point description |
Anti-PD antibody concentrations were presented as geometric mean concentrations (GMTs) and expressed in ELISA units per millilitre (EL.U/mL). “-9999” & “9999” as results for the Unknown GS Group are placeholder values for confidence interval results being not applicable/missing, as only 1 subject analyzed.
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End point type |
Primary
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End point timeframe |
Post Dose 4 at Week 13 (W13).
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| Notes [11] - 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: The scope of this primary endpoint was descriptive, no statistical analyses were conducted. |
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| No statistical analyses for this end point | ||||||||||||||||||||||||||
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End point title |
Number of patients with treatment response for anti-PD [12] | ||||||||||||||||||||
End point description |
Treatment response defined as:
For initially seronegative patients: post-administration antibody concentration ≥ 100 EL.U/mL
For initially seropositive patients: post-administration antibody concentration ≥ 2 fold the pre-vaccination antibody concentration
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End point type |
Primary
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End point timeframe |
Post Dose 4 at Week 13 (W13).
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| Notes [12] - 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: The scope of this primary endpoint was descriptive, no statistical analyses were conducted. |
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Number of patients with objective tumor response (OR) to MAGE-A3 ASCI study treatment | ||||||||||||||||||||||||||||||
End point description |
Response assessment was done based on a set of measurable lesions (MLs) identified at baseline as target lesions (TLs), and followed up until disease progression. Up to 5 MLs per organ & 10 in total were identified as TLs and measured at baseline, selected based on size (those with the longest diameter [LD]) and measurability; a sum of LDs for all TLs was calculated and reported as baseline sum LD, which was used to characterize objective tumor response (OR), OR being defined as either complete response (CR) and/or partial response (PR) post MAGE-A3 ASCI treatment. After identification, MLs and TLs were assessed as regards CR and PR definitions per Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
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End point type |
Secondary
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End point timeframe |
During the entire study, up to 5 years
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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End point title |
Number of patients with stable disease (SD) response to MAGE-A3 ASCI study treatment | |||||||||||||||||||||||||
End point description |
Assessment was done based on a set of MLs identified at baseline as TLs and NTLs (see above OR endpoint) followed up until disease progression. TLs and NTLs were assessed as regards matching or not SD-related definitions, 1) SD definitions per Response Evaluation Criteria in Solid Tumors (RECIST) criteria for TLs >= 20 mm and TLs both >= and < 20 mm, e. a. a) for TLs: SD = Neither sufficient shrinkage to qualify as a PR nor sufficient increase to qualify as PD, taking as references the smallest sum LD since treatment start. and b) for NTLs: SD = Persistence of one or more NTL; 2) following below criteria for TLs < 20mm e. a. a) for TLs: PR/SD = Neither sufficient shrinkage to qualify for CR nor sufficient increase, to qualify for PD taking as references the smallest sum LD since treatment start, and b) for NTLs: PR/SD = Persistence of one or more NTL.
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End point type |
Secondary
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End point timeframe |
During the entire study, up to 5 years
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| No statistical analyses for this end point | ||||||||||||||||||||||||||
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End point title |
Duration of stable disease (SD) response to MAGE-A3 ASCI study treatment | ||||||||||||||||||||
End point description |
Assessment was done based on a set of MLs identified at baseline as TLs and NTLs (see above OR endpoint) followed up until disease progression. Stable disease was defined as follows: 1) In case of target lesions (TL) greater than or equal to (≥) 20 mm: neither sufficient shrinkage to qualify for Partial Response nor sufficient increase to qualify for Progressive Disease, taking as references the sum of Longest Diameter (LD) of TL recorded previously but not necessarily at baseline; 2) In case of TL both less than 20 mm and ≥ 20 mm: Neither sufficient shrinkage to qualify as a PR nor sufficient increase to qualify as PD, taking as references the smallest sum LD since the start of the treatment. The minimal time interval required between 2 measurements for determination of SD was at least 12 weeks. “-9999” & “9999” are placeholder values for confidence interval results being not applicable/missing, as only 1 subject analyzed.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
During the entire study, up to 5 years
|
||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
||||||||||||||||||||||||||
End point title |
Number of patients with mixed response (MxR) to MAGE-A3 ASCI study treatment | |||||||||||||||||||||||||
End point description |
Assessment was done based on a set of MLs identified at baseline as TLs and NTLs (see above OR endpoint) followed up until disease progression. MLs were assessed as regards matching below MxR definitions. In case of evaluability per RECIST: a) MxR Type 1= at least (a.l.) 30% decrease in LD in a.l. one TL measured at baseline. Such response occurring in SD/PD status of LD of TL and without appearance of one or more new lesions = SD/PD with TL regression; b) MxR Type 2: appearance of one or more new lesions occurring in SD/PR status of LD of TL, and = SD/PR with new lesion. In case of non-evaluability per RECIST: a) MxR Type 1 = a clear decrease in diameters occurring in a.l. one TL measured at baseline. Such response occurring in SD/PD status of LD of (baseline) TL and without appearance of one or more new lesions = SD/PD with TL regression; b) MxR Type 2 = appearance of one or more new lesions occurring in SD/PR status of LD of TL = SD/PR with new lesion.
|
|||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||
End point timeframe |
During the entire study, up to 5 years
|
|||||||||||||||||||||||||
|
||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Time to treatment failure (TTF), by Gene Signature | ||||||||||||||||||||
End point description |
TTF was defined as withdrawal from treatment with the MAGE-A3 ASCI study product due to disease progression or death. TTF analysis was performed using the non-parametric Kaplan-Meier method. “-9999” & “9999” as results when about the Unknown GS Group are placeholder values for confidence interval results being not applicable/missing, as only 1 subject analyzed.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
During the entire study, up to 5 years
|
||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||
End point title |
Progression-free survival (PFS) for the overall population | ||||||||||
End point description |
PFS was defined and calculated as the time from first treatment to either the first progression of the disease or the date of death, whichever occurred first. In case a patient went off protocol treatment, the date of first documented progression (if applicable) was to be used as date of progression. Patients still alive with no evidence of disease progression at the time of their last visit or for whom date of first documented progression was not applicable, were censored at the time of the last examination. PFS analysis was performed using the non-parametric Kaplan-Meier method.
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
During the entire study, up to 5 years
|
||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||||||||||||
End point title |
Progression-free survival (PFS) by Gene Signature | ||||||||||||||||||||
End point description |
PFS was defined and calculated as the time from first treatment to either the first progression of the disease or the date of death, whichever occurred first. In case a patient went off protocol treatment, the date of first documented progression (if applicable) was to be used as date of progression. Patients still alive with no evidence of disease progression at the time of their last visit or for whom date of first documented progression was not applicable, were censored at the time of the last examination. PFS analysis was performed using the non-parametric Kaplan-Meier method. “-9999” & “9999” as results when about the Unknown GS Group are placeholder values for confidence interval results being not applicable/missing, as only 1 subject analyzed.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
During the entire study, up to 5 years
|
||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Progression-free survival (PFS) after slow progressive disease (SPD) by Gene Signature | ||||||||||||||||||||
End point description |
PFS after initial SPD was defined and calculated as the time from the time point at which the disease was the most advanced during the treatment to either a new progression of the disease or the date to death, whichever occurred first as another secondary outcome of this study. In that case, the largest diameter during the course of treatment was to be used as reference measurement. This outcome was defined to take into account the delay to induce an active immune response and the strict rules set up in this study to allow pursuing investigational treatment in case of SPD. PFS after SPD analysis was performed using the non-parametric Kaplan-Meier method. “-9999” & “9999” as results when about the Unknown GS Group are placeholder values for confidence interval results being not applicable/missing, as only 1 subject analyzed.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
During the entire study, up to 5 years.
|
||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
||||||||||||||||||||||||||
End point title |
Overall survival (OS) by Gene Signature | |||||||||||||||||||||||||
End point description |
OS was defined as the time from first treatment to the date of death. OS analysis was performed using the non-parametric Kaplan-Meier method. “-9999” & “9999” as results for the Unknown GS Group are placeholder values for confidence interval results being not applicable/missing, as only 1 subject analyzed.
|
|||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||
End point timeframe |
During the entire study, up to 5 years
|
|||||||||||||||||||||||||
|
||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal Alanine aminotransferase (ALT) values by maximum grade | ||||||||||||||||||||||||||||||||||||||||||
End point description |
The status of each patient as regards ALT laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0), G1 and G2. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
|
||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
During the entire study, up to 5 years
|
||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal Aspartate aminotransferase (AST) values by maximum grade | ||||||||||||||||||||||||||||||
End point description |
The status of each patient as regards AST laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
During the entire study, up to 5 years
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal Alkaline Phosphatase (ALK) values by maximum grade | ||||||||||||||||||||||||||||||
End point description |
The status of each patient as regards ALK laboratory values at baseline (SCR) up to study end(SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
During the entire study, up to 5 years
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal Bilirubine (BIL) values by maximum grade | ||||||||||||||||||||||||||||||
End point description |
The status of each patient as regards BIL laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Unknown (UNK) and Grade 0 (G0). CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
During the entire study, up to 5 years
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||||||||||||||
End point title |
Number of patients with abnormal Creatinine (CREA) values by maximum grade | ||||||||||||||||||
End point description |
The status of each patient as regards CREA laboratory values at baseline (SCR) up to study end(SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0). CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
During the entire study, up to 5 years
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal gamma-glutamyl transpeptidase (GGT) values by maximum grade | ||||||||||||||||||||||||||||||||||||||||||
End point description |
The status of each patient as regards GGT laboratory values at baseline (SCR) up to study end(SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0), G1 and G3. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
|
||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
During the entire study, up to 5 years
|
||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal Hemoglobin (HGB) values by maximum grade | ||||||||||||||||||||||||||||||
End point description |
The status of each patient as regards HGB laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
During the entire study, up to 5 years
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal Hypercalcemia (HCA) values by maximum grade | ||||||||||||||||||||||||||||||||||||||||
End point description |
The status of each patient as regards HCA laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Unknown (UNK), Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
|
||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||
End point timeframe |
During the entire study, up to 5 years
|
||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal Hyperkalemia (HKA) values by maximum grade | ||||||||||||||||||||||||||||||||||||||||||
End point description |
The status of each patient as regards HKA laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0), G1 and G2. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
|
||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
During the entire study, up to 5 years
|
||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal Hypernatremia (HNA) values by maximum grade | ||||||||||||||||||||||||||||||
End point description |
The status of each patient as regards HNA laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
During the entire study, up to 5 years
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal hypoalbuminemia(hAL) values by maximum grade | ||||||||||||||||||||||||||||||||||||||||
End point description |
The status of each patient as regards hAL laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Unknown (UNK), Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
|
||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||
End point timeframe |
During the entire study, up to 5 years
|
||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal hypocalcemia(hCA) values by maximum grade | ||||||||||||||||||||||||||||||||||||||||||
End point description |
The status of each patient as regards hCA laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Unknown (UNK), Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
|
||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
During the entire study, up to 5 years
|
||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal hypokalemia (hKA) values by maximum grade | ||||||||||||||||||||||||||||||
End point description |
The status of each patient as regards hKA laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
During the entire study, up to 5 years
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal hyponatremia (hNA) values by maximum grade | ||||||||||||||||||||||||||||||
End point description |
The status of each patient as regards hNA laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
During the entire study, up to 5 years
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal Leukocytes (LEU) values by maximum grade | ||||||||||||||||||||||||||||||
End point description |
The status of each patient as regards LEU laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
During the entire study, up to 5 years
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal Lymphopenia (LYM) values by maximum grade | ||||||||||||||||||||||||||||||
End point description |
The status of each patient as regards LYM laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
During the entire study, up to 5 years
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||||||||||||||
End point title |
Number of patients with abnormal Neutrophils (NEU) values by maximum grade | ||||||||||||||||||
End point description |
The status of each patient as regards NEU laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0). CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
During the entire study, up to 5 years
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal Partial Thromboplastin Time (PTT) values by maximum grade | ||||||||||||||||||||||||||||||
End point description |
The status of each patient as regards PTT laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
During the entire study, up to 5 years
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Number of patients with abnormal Platelets(PLT) values by maximum grade | ||||||||||||||||||||||||||||||
End point description |
The status of each patient as regards PLT laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).
|
||||||||||||||||||||||||||||||
End point type |
Secondary
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End point timeframe |
During the entire study, up to 5 years
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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End point title |
Number of patients with any adverse events (AEs) and with AEs by maximum grade | ||||||||||||||||||
End point description |
An AE was any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs reported are here below tabulated irrespective of grade (any), as well as graded by maximum grade reported according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. Maximum grade reported and tabulated were Grade 1 (G1), G2, G3, G4 and G5.
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End point type |
Secondary
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End point timeframe |
Within the 31-day follow-up period post treatment administration.
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Number of patients with any serious adverse events (SAEs) and with AEs by maximum grade | ||||||||||||||||||
End point description |
SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a patient, is a Grade 4 AE according to the CTCAE, version3.0. Events which were part of the natural course of the disease under study were captured as part of the clinical activity outcome variables in this study; therefore did not need to be reported as SAEs. Progression/recurrence of the tumor was recorded as part of the clinical assessment data collection, and deaths due to progressive disease was recorded on a specific form, but not as an SAE. SAEs reported are here below tabulated irrespective of grade (any), as well as graded by maximum grade reported according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. Maximum grade reported and tabulated were Grade 1 (G1), G2, G3, G4 and G5.
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End point type |
Secondary
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End point timeframe |
Within the 31-day follow-up period post treatment administration.
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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 |
SAEs: From screening (SCR) up to study end; AEs: Within the 31-day follow-up period post treatment administration, up to study end.
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Adverse event reporting additional description |
The occurrence of reported AEs (all/related) was not available and is encoded as equal to the number of subjects affected.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1
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Reporting groups
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Reporting group title |
MAGE-A3 Group
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Reporting group description |
Patients planned to receive intramuscularly up to 24 doses of MAGE-A3 ASCI (the study product), in 4 cycles | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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10 Jul 2008 |
The changes following this Amendment concern:
• The threshold value of LDH as inclusion criterion
• The procedures to be performed at each visit for treatment administration
|
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02 Mar 2009 |
The changes following this amendment concern:
• The possibility of taking a new tumor biopsy in case the results of the analysis of the biopsies originally taken are inconclusive.
• Clarification that MAGE-A3 testing and gene profiling of newly dissected tumors in case of disease progression require specific informed consent by the patients.
• Clarification of the number of target lesions
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16 Oct 2009 |
The changes following this amendment concern:
• The number of patients to be enrolled has been increased from 20 to 40 in order to assess the gene profile data in patients who also receive chemotherapy. A pre-specified gene signature was identified in previous studies, but has not yet been assessed in patients receiving chemotherapy. Based on existing data, it is estimated that approximately 50% of patients will have a pre-specified gene signature. Therefore, the sample size should be doubled to have approximately 20 patients with and 20 patients without the pre-specified gene signature. Final analyses will be assessed in the overall population and in subsets with or without the pre-specified gene signature. As many patients currently enrolled in the study have agreed to allow gene profiling of their tumor sample it will remain an optional procedure.
• The duration of follow-up for survival, disease progression and SAEs related to study participation and concurrent medication has been extended from 4 to 5 years after first treatment administration to obtain continued information regarding the patients’ health status after the treatment phase.
• Overall survival has been added as a secondary endpoint.
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16 Jul 2010 |
The changes following this amendment concern the avoidance of repeating procedures (biopsy and tumor imaging) during the screening phase, which may already have been performed recently prior to screening as part of local routine practice or in relation to another research study.
It has also been made clear that any second-line therapy and not only second-line chemotherapy after the study treatment is of interest.
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Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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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 | |||||||
