Back to resultsStudy of GSK2132231A Antigen-Specific Cancer Immunotherapeutic in Patients With Inoperable Metastatic Cutaneous Melanoma
Primary Purpose
Melanoma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Immunotherapeutic GSK2132231A
Sponsored by
About this trial
This is an interventional treatment trial for Melanoma focused on measuring ASCI (Antigen-Specific Cancer Immunotherapeutic), MAGE-A3, Malignant melanoma, Cancer immunotherapeutic
Eligibility Criteria
Inclusion Criteria:
The patient (male or female) has histologically proven, measurable metastatic cutaneous melanoma in one of the following stages according to the American Joint Committee on Cancer classification of 2002:
- Stage III in transit, or
- Stage III unresectable, or
- Stage IV M1a.
- There has been documented progression of the patient's disease within the 12 weeks before the first administration of study treatment.
- The patient presents at screening with at least 3 tumor lesions of diameter >= 0.5 mm.
- Written informed consent has been obtained from the patient before the performance of any protocol-specific procedure.
- The patient is >= 18 years of age at the time of signature of informed consent.
- The patient's tumor shows expression of MAGE-A3 gene in at least one of the two tumor biopsies performed at baseline.
- The patient's ECOG performance status is 0 or 1.
- The patient has normal organ functions, as assessed by standard laboratory criteria.
- If the patient is female, she must be of non-childbearing potential, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to administration of study treatment, have a negative pregnancy test and continue such precautions during the entire study treatment period and for 2 months after completion of the treatment injection series.
- In the view of the investigator, the patient can and will comply with the requirements of the protocol.
Exclusion Criteria:
- The patient has at any time received systemic (bio)-chemotherapy
- The patient is scheduled to receive any anti-cancer specific treatment, including radiotherapy, immunotherapy, chemotherapy and immunomodulating agents.
- The patient requires concomitant treatment with systemic corticosteroids, or any other immunosuppressive agents.
- The patient has received any cancer immunotherapeutic containing a MAGE A3 antigen or any cancer immunotherapeutic for his/her metastatic disease.
- Use of any investigational or non-registered product (drug or vaccine) other than the study treatment within the 30 days preceding the first dose of study treatment, or planned use during the study period.
- The patient has (or has had) previous or concomitant malignancies at other sites, except effectively treated malignancy that is considered by the investigator highly likely to have been cured.
- History of allergic disease or reactions likely to be exacerbated by any component of the study investigational product.
- The patient has an autoimmune disease such as, but not limited to, neuroinflammatory autoimmune diseases, systemic lupus erythematosus, and inflammatory bowel disease
- The patient has a family history of congenital or hereditary immunodeficiency.
- The patient is known to be positive for the human immunodeficiency virus (HIV).
- The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent, or to comply with the study procedures.
- The patient has concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.
- For female patients: the patient is pregnant or lactating.
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
GSK2132231A Group
Arm Description
Subjects, male or female, 18 years of age or older, received up to 24 doses of GSK2132231A intramuscularly in 4 cycles. In Cycle 1 (ending Week 13) 6 doses were administered at 2-week intervals; in Cycle 2 (ending Week 32) 6 doses at 3-week intervals; in Cycle 3 (ending Week 54) 4 doses at 6-week intervals and in Cycle 4 4 doses at 12-week intervals, starting 12 weeks after end of Cycle 3, followed by, after an interruption of treatment of 6 months, 4 doses at 24-week intervals.
Outcomes
Primary Outcome Measures
Number of Patients With Objective Tumor Response (OR) to GSK2132231A Study Treatment
OR was defined as the best Overall Response (OR) in a patient. OR = Complete Response (CR) + Partial Response (PR). Responses were categorized as CR, PR, stable disease (SD), SD/PR, progressive disease (PD) and non-evaluable (NE). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by Magnetic-resonance imaging: Complete Response (CR) = disappearance of all target lesions; Partial Response (PR) = ≥30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD) = neither sufficient shrinkage to be PR, not sufficient increase to qualify for Progressive Disease (PD); PD = ≥20% increase in the sum of largest diameter for target lesions. Best objective response = PR or CR. Disease control = CR, or PR, or SD, or SD/PR.
Number of Patients With Mixed Response (MR) to GSK2132231A
Assessment was done based on a set of measurable lesions (MLs) identified at baseline as target lesions (TLs) and non-TLs (NTL) followed up until disease progression. MLs assessed for matching below MR definitions. If evaluability per RECIST: a) MR 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) MR Type 2: appearance of one or more new lesions occurring in SD/PR status of LD of TL (= SD/PR with new lesion). If non-evaluability per RECIST (due to LD<20mm): a) MR 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) MR Type 2 = appearance of one or more new lesions occurring in SD/PR status of LD of TL (= SD/PR with new lesion).
Time to Treatment Failure (TTF), by Gene Signature
TTF was defined as withdrawal from treatment with the GSK2132231A study product due to disease progression or death. TTF analysis was performed using the non-parametric Kaplan-Meier method.
Anti-MAGE-A3 Antibody Concentrations
Anti-MAGE-A3 antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in ELISA units per millilitre (EL.U/mL). A seropositive patient was defined as a patient whose anti-MAGE-A3 antibody concentration was greater than or equal to 27 EL.U/mL. D=Day W=Week
Number of Seroconverted Patients for Anti-MAGE-A3
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 ≥ 27 EL.U/mL.
Number of Patients With Treatment Response for Anti-MAGE-A3 Antibodies
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
Geometric Mean Titers of Anti-MAGE-A3 Specific CD4+ and CD8+ T-cells Concentrations After Immunization
This endpoint presents the geometric mean concentration, expressed in titers, of anti-MAGE-A3 specific CD4+ and CD8+ T-cells. These specific T-cells included the cluster of differentiation 4+ (CD4+) and CD8+ T-cells producing cytokines Tumor Necrosis Factor-alpha (TNF-α) and/or Interferon-gamma (INF-γ).
Number of Patients With CD4+ and CD8+ T Cell Frequency ≥ 1.24 Cut-off
A patient was considered as a cellular mediated immune (CMI) responder if there was an increased amount of antigen-specific T-cells after immunization as compared to the patient's baseline value. These specific T-cells included the cluster of differentiation 4+ (CD4+) and CD8+ T-cells producing cytokines Tumor Necrosis Factor-alpha (TNF-α) and/or Interferon-gamma (INF-γ).
Number of Patients With a Cellular Response (Anti-MAGE-A3 Specific CD4+ and CD8+ T-cells Concentrations After Immunization)
A patient was considered as a cellular mediated immune (CMI) responder if there was an increased amount of antigen-specific T-cells after immunization as compared to the patient's baseline value. These specific T-cells included the cluster of differentiation 4+ (CD4+) and CD8+ T-cells producing cytokines Tumor Necrosis Factor-alpha (TNF-α) and/or Interferon-gamma (INF-γ).
Number of Patients Reported With Antigen Specific Cancer Immunotherapeutics (ASCI)-Related grade3/4 Adverse Events (AEs) According to the Common Terminology Criteria (CTCAE) Version 3.0.
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. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse. AEs may include pre- or post-treatment events that occur as a result of protocol-mandated procedures (i.e. invasive procedures, modification of patient's previous therapeutic regimen).
Number of Patients Reported With Serious Adverse Events (SAEs)
Serious adverse events (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. 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.
Number of Patients With Abnormal Alanine Aminotransferase (ALT) Values by Maximum Grade
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. ALT - SCR G0; SE G3 = ALT with no abnormality/normal value at screening and with Severe abnormality at study end].
Number of Patients With Abnormal Aspartate Aminotransferase (AST) Values by Maximum Grade
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. AST - SCR G0; SE G3 = AST with no abnormality/normal value at screening and with Severe abnormality at study end].
Number of Patients With Abnormal Alkaline Phosphatase (ALK) Values by Maximum Grade
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. ALK - SCR G0; SE G3 = ALK with no abnormality/normal value at screening and with Severe abnormality at study end].
Number of Patients With Abnormal Bilirubine (BIL) Values by Maximum Grade
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. BIL - SCR G0; SE G3 = BIL with no abnormality/normal value at screening and with Severe abnormality at study end].
Number of Patients With Abnormal Creatinine (CREA) Values by Maximum Grade
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. CREA - SCR G0; SE G3 = CREA with no abnormality/normal value at screening and with Severe abnormality at study end].
Number of Patients With Abnormal Gamma-glutamyl Transpeptidase (GGT) Values by Maximum Grade
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. GGT - SCR G0; SE G3 = GGT with no abnormality/normal value at screening and with Severe abnormality at study end].
Number of Patients With Abnormal Hemoglobin (HGB) Values by Maximum Grade
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. HGB - SCR G0; SE G3 = HGB with no abnormality/normal value at screening and with Severe abnormality at study end].
Number of Patients With Abnormal Hypercalcemia (HCA) Values by Maximum Grade
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. HCA - SCR G0; SE G3 = HCA with no abnormality/normal value at screening and with Severe abnormality at study end].
Number of Patients With Abnormal Hyperkalemia (HKA) Values by Maximum Grade
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. HKA - SCR G0; SE G3 = HKA with no abnormality/normal value at screening and with Severe abnormality at study end].
Number of Patients With Abnormal Hypernatremia (HNA) Values by Maximum Grade
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. HNA - SCR G0; SE G3 = HNA with no abnormality/normal value at screening and with Severe abnormality at study end].
Number of Patients With Abnormal Hypoalbuminemia (hAL) Values by Maximum Grade
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. hAL - SCR G0; SE G3 = hAL with no abnormality/normal value at screening and with Severe abnormality at study end].
Number of Patients With Abnormal Hypocalcemia (hCA) Values by Maximum Grade
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. hCA - SCR G0; SE G3 = hCA with no abnormality/normal value at screening and with Severe abnormality at study end].
Number of Patients With Abnormal Hypokalemia (hKA) Values by Maximum Grade
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. hKA - SCR G0; SE G3 = hKA with no abnormality/normal value at screening and with Severe abnormality at study end].
Number of Patients With Abnormal Hyponatremia (hNA) Values by Maximum Grade
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. hNA - SCR G0; SE G3 = hNA with no abnormality/normal value at screening and with Severe abnormality at study end].
Number of Patients With Abnormal Leukocytes (LEU) Values by Maximum Grade
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. LEU - SCR G0; SE G3 = LEU with no abnormality/normal value at screening and with Severe abnormality at study end].
Number of Patients With Abnormal Lymphopenia (LYM) Values by Maximum Grade
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. LYM - SCR G0; SE G3 = LYM with no abnormality/normal value at screening and with Severe abnormality at study end].
Number of Patients With Abnormal Neutrophils (NEU) Values by Maximum Grade
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. NEU - SCR G0; SE G3 = NEU with no abnormality/normal value at screening and with Severe abnormality at study end].
Number of Patients With Abnormal Platelets (PLT) Values by Maximum Grade
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. PLT - SCR G0; SE G3 = PLT with no abnormality/normal value at screening and with Severe abnormality at study end].
Number of Patients With Any Adverse Events (AEs) and With AEs by Maximum Grade
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) - Mild AE, G2 - Moderate AE, G3 - Severe AE, G4 - Life threatening/Disabling AE and G5 - Death related to AE.
Number of Patients With Any AE(s) and With AEs by Maximum Grade, Related to Treatment Administration
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) - Mild AE, G2 - Moderate AE, G3 - Severe AE, G4 - Life threatening/Disabling AE and G5 - Death related to AE.
Number of Patients With Any Serious Adverse Events (SAEs) and With SAEs by Maximum Grade
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. 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 CTC Adverse event terminology, version 3.0. Maximum grade reported and tabulated were Grade 1 (G1) - Mild SAE, G2 - Moderate SAE, G3 - Severe SAE, G4 - Life threatening/Disabling SAE and G5 - Death related to SAE.
Number of Patients With Any Serious Adverse Events (SAEs) and With SAEs by Maximum Grade, Related to Treatment Administration
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. 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 CTC Adverse event terminology, version 3.0. Maximum grade reported and tabulated were Grade 1 (G1) - Mild SAE, G2 - Moderate SAE, G3 - Severe SAE, G4 - Life threatening/Disabling SAE and G5 - Death related to SAE.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00896480
Brief Title
Study of GSK2132231A Antigen-Specific Cancer Immunotherapeutic in Patients With Inoperable Metastatic Cutaneous Melanoma
Official Title
Clinical Activity, Safety and Immunogenic Properties of Cancer Immunotherapeutic GSK2132231A in Patients With Unresectable and Progressive Metastatic Cutaneous Melanoma
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
May 19, 2009 (Actual)
Primary Completion Date
November 3, 2014 (Actual)
Study Completion Date
November 3, 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The clinical objective of this clinical trial is to examine the clinical activity in terms of tumor response and time to treatment failure of the immunotherapeutic product GSK2132231A when given to patients with unresectable and progressive metastatic cutaneous melanoma. The safety of the treatment will also be assessed just as its immunogenicity in terms of the humoral and cellular immune response induced by the GSK2132231A immunotherapeutic. Translational research objectives are to assess the effects of the study treatment in terms of various biological variables.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma
Keywords
ASCI (Antigen-Specific Cancer Immunotherapeutic), MAGE-A3, Malignant melanoma, Cancer immunotherapeutic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GSK2132231A Group
Arm Type
Experimental
Arm Description
Subjects, male or female, 18 years of age or older, received up to 24 doses of GSK2132231A intramuscularly in 4 cycles. In Cycle 1 (ending Week 13) 6 doses were administered at 2-week intervals; in Cycle 2 (ending Week 32) 6 doses at 3-week intervals; in Cycle 3 (ending Week 54) 4 doses at 6-week intervals and in Cycle 4 4 doses at 12-week intervals, starting 12 weeks after end of Cycle 3, followed by, after an interruption of treatment of 6 months, 4 doses at 24-week intervals.
Intervention Type
Biological
Intervention Name(s)
Immunotherapeutic GSK2132231A
Other Intervention Name(s)
MAGE-A3 ASCI
Intervention Description
Administration by intramuscular injection
Primary Outcome Measure Information:
Title
Number of Patients With Objective Tumor Response (OR) to GSK2132231A Study Treatment
Description
OR was defined as the best Overall Response (OR) in a patient. OR = Complete Response (CR) + Partial Response (PR). Responses were categorized as CR, PR, stable disease (SD), SD/PR, progressive disease (PD) and non-evaluable (NE). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by Magnetic-resonance imaging: Complete Response (CR) = disappearance of all target lesions; Partial Response (PR) = ≥30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD) = neither sufficient shrinkage to be PR, not sufficient increase to qualify for Progressive Disease (PD); PD = ≥20% increase in the sum of largest diameter for target lesions. Best objective response = PR or CR. Disease control = CR, or PR, or SD, or SD/PR.
Time Frame
From Pre-treatment (up to 4 weeks before first treatment) to study end (Year 4), each patient being censored out of the analysis at 1st report of disease progression in assessed lesions
Title
Number of Patients With Mixed Response (MR) to GSK2132231A
Description
Assessment was done based on a set of measurable lesions (MLs) identified at baseline as target lesions (TLs) and non-TLs (NTL) followed up until disease progression. MLs assessed for matching below MR definitions. If evaluability per RECIST: a) MR 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) MR Type 2: appearance of one or more new lesions occurring in SD/PR status of LD of TL (= SD/PR with new lesion). If non-evaluability per RECIST (due to LD<20mm): a) MR 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) MR Type 2 = appearance of one or more new lesions occurring in SD/PR status of LD of TL (= SD/PR with new lesion).
Time Frame
From Pre-treatment (up to 4 weeks before first treatment) to study end (Year 4), each patient being censored out of the analysis at 1st report of disease progression in assessed lesions
Title
Time to Treatment Failure (TTF), by Gene Signature
Description
TTF was defined as withdrawal from treatment with the GSK2132231A study product due to disease progression or death. TTF analysis was performed using the non-parametric Kaplan-Meier method.
Time Frame
From Pre-treatment (up to 4 weeks before first treatment) to study end (Year 4), each patient being censored out of the analysis at 1st report of disease progression or death
Title
Anti-MAGE-A3 Antibody Concentrations
Description
Anti-MAGE-A3 antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed in ELISA units per millilitre (EL.U/mL). A seropositive patient was defined as a patient whose anti-MAGE-A3 antibody concentration was greater than or equal to 27 EL.U/mL. D=Day W=Week
Time Frame
From Pre-treatment (up to 4 weeks before first treatment) to Concluding visit (CCL: at Week 196 + 30 to 37 days for patients completing the treatment, 1 month after the last Dose administered for patients withdrawn from study treatment before completion)
Title
Number of Seroconverted Patients for Anti-MAGE-A3
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 ≥ 27 EL.U/mL.
Time Frame
From Pre-treatment (up to 4 weeks before first treatment) to Concluding visit (CCL: at Week 196 + 30 to 37 days for patients completing the treatment, 1 month after the last Dose administered for patients withdrawn from study treatment before completion)
Title
Number of Patients With Treatment Response for Anti-MAGE-A3 Antibodies
Description
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
Time Frame
From Day 2 to Concluding visit (CCL:at Week 196 + 30 to 37 days for patients completing the treatment, 1 month after the last Dose administered for patients withdrawn from study treatment before completion)
Title
Geometric Mean Titers of Anti-MAGE-A3 Specific CD4+ and CD8+ T-cells Concentrations After Immunization
Description
This endpoint presents the geometric mean concentration, expressed in titers, of anti-MAGE-A3 specific CD4+ and CD8+ T-cells. These specific T-cells included the cluster of differentiation 4+ (CD4+) and CD8+ T-cells producing cytokines Tumor Necrosis Factor-alpha (TNF-α) and/or Interferon-gamma (INF-γ).
Time Frame
From Pre-treatment (up to 4 weeks before first treatment) to Concluding visit (CCL: at Week 196 + 30 to 37 days for patients completing the treatment, 1 month after the last Dose administered for patients withdrawn from study treatment before completion)
Title
Number of Patients With CD4+ and CD8+ T Cell Frequency ≥ 1.24 Cut-off
Description
A patient was considered as a cellular mediated immune (CMI) responder if there was an increased amount of antigen-specific T-cells after immunization as compared to the patient's baseline value. These specific T-cells included the cluster of differentiation 4+ (CD4+) and CD8+ T-cells producing cytokines Tumor Necrosis Factor-alpha (TNF-α) and/or Interferon-gamma (INF-γ).
Time Frame
From Pre-treatment (up to 4 weeks before first treatment) to Concluding visit (CCL: at Week 196 + 30 to 37 days for patients completing the treatment, 1 month after the last Dose administered for patients withdrawn from study treatment before completion)
Title
Number of Patients With a Cellular Response (Anti-MAGE-A3 Specific CD4+ and CD8+ T-cells Concentrations After Immunization)
Description
A patient was considered as a cellular mediated immune (CMI) responder if there was an increased amount of antigen-specific T-cells after immunization as compared to the patient's baseline value. These specific T-cells included the cluster of differentiation 4+ (CD4+) and CD8+ T-cells producing cytokines Tumor Necrosis Factor-alpha (TNF-α) and/or Interferon-gamma (INF-γ).
Time Frame
From Week 5 to Concluding visit (CCL: at Week 196 + 30 to 37 days for patients completing the treatment, 1 month after the last Dose administered for patients withdrawn from study treatment before completion)
Title
Number of Patients Reported With Antigen Specific Cancer Immunotherapeutics (ASCI)-Related grade3/4 Adverse Events (AEs) According to the Common Terminology Criteria (CTCAE) Version 3.0.
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. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse. AEs may include pre- or post-treatment events that occur as a result of protocol-mandated procedures (i.e. invasive procedures, modification of patient's previous therapeutic regimen).
Time Frame
Within the 31-day (Days 0-30) post-administration periods
Title
Number of Patients Reported With Serious Adverse Events (SAEs)
Description
Serious adverse events (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. 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.
Time Frame
During the entire study period (from Day 0 to CCL: at Week 196 + 30 to 37 days for patients completing the treatment, 1 month after the last Dose administered for patients withdrawn from study treatment before completion
Title
Number of Patients With Abnormal Alanine Aminotransferase (ALT) Values by Maximum Grade
Description
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. ALT - SCR G0; SE G3 = ALT with no abnormality/normal value at screening and with Severe abnormality at study end].
Time Frame
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
Title
Number of Patients With Abnormal Aspartate Aminotransferase (AST) Values by Maximum Grade
Description
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. AST - SCR G0; SE G3 = AST with no abnormality/normal value at screening and with Severe abnormality at study end].
Time Frame
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
Title
Number of Patients With Abnormal Alkaline Phosphatase (ALK) Values by Maximum Grade
Description
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. ALK - SCR G0; SE G3 = ALK with no abnormality/normal value at screening and with Severe abnormality at study end].
Time Frame
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
Title
Number of Patients With Abnormal Bilirubine (BIL) Values by Maximum Grade
Description
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. BIL - SCR G0; SE G3 = BIL with no abnormality/normal value at screening and with Severe abnormality at study end].
Time Frame
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
Title
Number of Patients With Abnormal Creatinine (CREA) Values by Maximum Grade
Description
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. CREA - SCR G0; SE G3 = CREA with no abnormality/normal value at screening and with Severe abnormality at study end].
Time Frame
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
Title
Number of Patients With Abnormal Gamma-glutamyl Transpeptidase (GGT) Values by Maximum Grade
Description
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. GGT - SCR G0; SE G3 = GGT with no abnormality/normal value at screening and with Severe abnormality at study end].
Time Frame
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
Title
Number of Patients With Abnormal Hemoglobin (HGB) Values by Maximum Grade
Description
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. HGB - SCR G0; SE G3 = HGB with no abnormality/normal value at screening and with Severe abnormality at study end].
Time Frame
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
Title
Number of Patients With Abnormal Hypercalcemia (HCA) Values by Maximum Grade
Description
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. HCA - SCR G0; SE G3 = HCA with no abnormality/normal value at screening and with Severe abnormality at study end].
Time Frame
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
Title
Number of Patients With Abnormal Hyperkalemia (HKA) Values by Maximum Grade
Description
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. HKA - SCR G0; SE G3 = HKA with no abnormality/normal value at screening and with Severe abnormality at study end].
Time Frame
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
Title
Number of Patients With Abnormal Hypernatremia (HNA) Values by Maximum Grade
Description
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. HNA - SCR G0; SE G3 = HNA with no abnormality/normal value at screening and with Severe abnormality at study end].
Time Frame
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
Title
Number of Patients With Abnormal Hypoalbuminemia (hAL) Values by Maximum Grade
Description
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. hAL - SCR G0; SE G3 = hAL with no abnormality/normal value at screening and with Severe abnormality at study end].
Time Frame
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
Title
Number of Patients With Abnormal Hypocalcemia (hCA) Values by Maximum Grade
Description
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. hCA - SCR G0; SE G3 = hCA with no abnormality/normal value at screening and with Severe abnormality at study end].
Time Frame
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
Title
Number of Patients With Abnormal Hypokalemia (hKA) Values by Maximum Grade
Description
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. hKA - SCR G0; SE G3 = hKA with no abnormality/normal value at screening and with Severe abnormality at study end].
Time Frame
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
Title
Number of Patients With Abnormal Hyponatremia (hNA) Values by Maximum Grade
Description
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. hNA - SCR G0; SE G3 = hNA with no abnormality/normal value at screening and with Severe abnormality at study end].
Time Frame
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
Title
Number of Patients With Abnormal Leukocytes (LEU) Values by Maximum Grade
Description
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. LEU - SCR G0; SE G3 = LEU with no abnormality/normal value at screening and with Severe abnormality at study end].
Time Frame
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
Title
Number of Patients With Abnormal Lymphopenia (LYM) Values by Maximum Grade
Description
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. LYM - SCR G0; SE G3 = LYM with no abnormality/normal value at screening and with Severe abnormality at study end].
Time Frame
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
Title
Number of Patients With Abnormal Neutrophils (NEU) Values by Maximum Grade
Description
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. NEU - SCR G0; SE G3 = NEU with no abnormality/normal value at screening and with Severe abnormality at study end].
Time Frame
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
Title
Number of Patients With Abnormal Platelets (PLT) Values by Maximum Grade
Description
The status of each patient was collected and graded according to the Common Terminology Criteria Adverse Event (CTCAE v.03) terminology. Gradings were: G0 (normal value), G1 (Mild abnormality), G2 (Moderate abnormality), G3 (Severe abnormality), G4 (Life-threatening/Disabling abnormality), Unknown abnormality (UNK).
The post-treatment values, at Study End (SE) were presented versus baseline values, at Screening (SCR). [e.g. PLT - SCR G0; SE G3 = PLT with no abnormality/normal value at screening and with Severe abnormality at study end].
Time Frame
From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
Title
Number of Patients With Any Adverse Events (AEs) and With AEs by Maximum Grade
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) - Mild AE, G2 - Moderate AE, G3 - Severe AE, G4 - Life threatening/Disabling AE and G5 - Death related to AE.
Time Frame
Within the 31-day (Day 0-30) follow-up period post treatment administration.
Title
Number of Patients With Any AE(s) and With AEs by Maximum Grade, Related to Treatment Administration
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) - Mild AE, G2 - Moderate AE, G3 - Severe AE, G4 - Life threatening/Disabling AE and G5 - Death related to AE.
Time Frame
Within the 31-day (Day 0-30) follow-up period post treatment administration.
Title
Number of Patients With Any Serious Adverse Events (SAEs) and With SAEs by Maximum Grade
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. 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 CTC Adverse event terminology, version 3.0. Maximum grade reported and tabulated were Grade 1 (G1) - Mild SAE, G2 - Moderate SAE, G3 - Severe SAE, G4 - Life threatening/Disabling SAE and G5 - Death related to SAE.
Time Frame
Within the 31-day (Day 0-30) follow-up period post treatment administration.
Title
Number of Patients With Any Serious Adverse Events (SAEs) and With SAEs by Maximum Grade, Related to Treatment Administration
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. 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 CTC Adverse event terminology, version 3.0. Maximum grade reported and tabulated were Grade 1 (G1) - Mild SAE, G2 - Moderate SAE, G3 - Severe SAE, G4 - Life threatening/Disabling SAE and G5 - Death related to SAE.
Time Frame
Within the 31-day (Day 0-30) follow-up period post treatment administration.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
The patient (male or female) has histologically proven, measurable metastatic cutaneous melanoma in one of the following stages according to the American Joint Committee on Cancer classification of 2002:
Stage III in transit, or
Stage III unresectable, or
Stage IV M1a.
There has been documented progression of the patient's disease within the 12 weeks before the first administration of study treatment.
The patient presents at screening with at least 3 tumor lesions of diameter >= 0.5 mm.
Written informed consent has been obtained from the patient before the performance of any protocol-specific procedure.
The patient is >= 18 years of age at the time of signature of informed consent.
The patient's tumor shows expression of MAGE-A3 gene in at least one of the two tumor biopsies performed at baseline.
The patient's ECOG performance status is 0 or 1.
The patient has normal organ functions, as assessed by standard laboratory criteria.
If the patient is female, she must be of non-childbearing potential, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to administration of study treatment, have a negative pregnancy test and continue such precautions during the entire study treatment period and for 2 months after completion of the treatment injection series.
In the view of the investigator, the patient can and will comply with the requirements of the protocol.
Exclusion Criteria:
The patient has at any time received systemic (bio)-chemotherapy
The patient is scheduled to receive any anti-cancer specific treatment, including radiotherapy, immunotherapy, chemotherapy and immunomodulating agents.
The patient requires concomitant treatment with systemic corticosteroids, or any other immunosuppressive agents.
The patient has received any cancer immunotherapeutic containing a MAGE A3 antigen or any cancer immunotherapeutic for his/her metastatic disease.
Use of any investigational or non-registered product (drug or vaccine) other than the study treatment within the 30 days preceding the first dose of study treatment, or planned use during the study period.
The patient has (or has had) previous or concomitant malignancies at other sites, except effectively treated malignancy that is considered by the investigator highly likely to have been cured.
History of allergic disease or reactions likely to be exacerbated by any component of the study investigational product.
The patient has an autoimmune disease such as, but not limited to, neuroinflammatory autoimmune diseases, systemic lupus erythematosus, and inflammatory bowel disease
The patient has a family history of congenital or hereditary immunodeficiency.
The patient is known to be positive for the human immunodeficiency virus (HIV).
The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent, or to comply with the study procedures.
The patient has concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.
For female patients: the patient is pregnant or lactating.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Brussels
ZIP/Postal Code
1200
Country
Belgium
Facility Name
GSK Investigational Site
City
Brussel
ZIP/Postal Code
1090
Country
Belgium
Facility Name
GSK Investigational Site
City
Wilrijk
ZIP/Postal Code
2610
Country
Belgium
Facility Name
GSK Investigational Site
City
Caen
ZIP/Postal Code
14033
Country
France
Facility Name
GSK Investigational Site
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
GSK Investigational Site
City
Paris Cedex 10
ZIP/Postal Code
75475
Country
France
Facility Name
GSK Investigational Site
City
Reims
ZIP/Postal Code
51092
Country
France
Facility Name
GSK Investigational Site
City
Villejuif
ZIP/Postal Code
94805
Country
France
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
IPD is available via the Clinical Study Data Request site (click on the link provided below)
IPD Sharing Time Frame
IPD is available via the Clinical Study Data Request site (click on the link provided below)
IPD Sharing Access Criteria
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
IPD Sharing URL
https://www.clinicalstudydatarequest.com/Posting.aspx?ID=16043
Citations:
PubMed Identifier
30094070
Citation
Baurain JF, Robert C, Mortier L, Neyns B, Grange F, Lebbe C, Ulloa-Montoya F, De Sousa Alves PM, Gillet M, Louahed J, Jarnjak S, Lehmann FF. Association of homogeneous inflamed gene signature with a better outcome in patients with metastatic melanoma treated with MAGE-A3 immunotherapeutic. ESMO Open. 2018 Jul 25;3(5):e000384. doi: 10.1136/esmoopen-2018-000384. eCollection 2018.
Results Reference
background
Links:
URL
https://clinicalstudydatarequest.com
Description
IPD for this study will be made available via the Clinical Study Data Request site.
Learn more about this trial
Study of GSK2132231A Antigen-Specific Cancer Immunotherapeutic in Patients With Inoperable Metastatic Cutaneous Melanoma
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