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Evaluation of a New Vaccine Treatment for Patients With Metastatic Skin Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01149343
Recruitment Status : Completed
First Posted : June 23, 2010
Results First Posted : August 31, 2018
Last Update Posted : April 27, 2020
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE June 22, 2010
First Posted Date  ICMJE June 23, 2010
Results First Submitted Date  ICMJE December 19, 2017
Results First Posted Date  ICMJE August 31, 2018
Last Update Posted Date April 27, 2020
Actual Study Start Date  ICMJE July 2, 2010
Actual Primary Completion Date February 11, 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 15, 2018)
  • Number of Patients With Dose-limiting Toxicity (Phase I) [ Time Frame: During the study treatment (up to Year 4), for all patients ]
    The dose-limiting toxicities (DLT) were defined as follows:
    • An Antigen-Specific Cancer Immunotherapeutic (ASCI) related or possibly ASCI related grade 3 or higher toxicity. Grade 3 myalgia, arthralgia, headache, fever, rigors/chills and fatigue (including lethargy, malaise and asthenia) persisting for 48 hours despite therapy.
    • An ASCI related or possibly ASCI related grade 2 or higher allergic reaction occurring within 24 hours following the ASCI administration.
    • An ASCI related or possibly ASCI related decrease in renal function, with a creatinine clearance lower than (<) 40 milliliters per minute (mL/min).
    • An ASCI-related or possibly ASCI-related symptomatic and confirmed adrenal insufficiency. The grading used was defined according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0: Grade 3 DLT = severe DLT. Related = DLT considered by investigator as possibly related to product administration.
  • Percentage of Patients With Anti-PReferentially Expressed Antigen of MElanoma (Anti-PRAME) Humoral Immune Response (Phase I) [ Time Frame: After the administration of dose 4, at Week 8 ]
    A seronegative/seropositive patient for anti-PRAME antibodies was a patient with antibody concentration lower (<)/ higher than or equal to (≥) cut-off level. Humoral immune response was defined as a) if baseline concentration < cut-off level: post treatment concentration ≥ cut-off level, or b) if baseline concentration ≥ cut-off level: post treatment concentration at least twice the baseline value. Cut-off values for seropositivity (by enzyme-linked immunosorbent assay [ELISA]) were 12 ELISA Units per milliliter (EL.U/mL).
  • Number of Patients With Best Overall Response to Study Treatment (Phase II) [ Time Frame: During the entire study period - up to Year 4 + 1 month post last study treatment administration ]
    The best overall response is the best response recorded from the start of the treatment until disease progression (taking as reference for progressive disease the smallest measurements recorded since the treatment started). In general the patient's best response assignment depended on the achievement of both measurement and confirmation criteria. The best overall response includes the complete response (CR) defined as disappearance of all targeted/non-targeted lesions and partial response (PR) defined as at least 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD and persistence of one or more non-targeted lesion(s).
Original Primary Outcome Measures  ICMJE
 (submitted: June 22, 2010)
  • Occurrence of dose limiting toxicity (Phase 1 and 2) during study treatment/follow-up [ Time Frame: During the study treatment (up to 4 years) and until the end of a 1 year follow-up. ]
  • Anti-PRAME humoral immune response (Phase 1) [ Time Frame: After the administration of dose 4 (Week 8) ]
  • Clinical activity of GSK2302025A (Phase 2) in terms of objective clinical responses (complete (CR) or partial (PR) response) [ Time Frame: At week 12 ]
  • Clinical activity of GSK2302025A (Phase 2) in terms of objective clinical responses (complete (CR) or partial (PR) response) [ Time Frame: At week 23 ]
  • Clinical activity of GSK2302025A (Phase 2) in terms of objective clinical responses (complete (CR) or partial (PR) response) [ Time Frame: At week 32 ]
  • Clinical activity of GSK2302025A (Phase 2) in terms of objective clinical responses (complete (CR) or partial (PR) response) [ Time Frame: At week 54 ]
  • Clinical activity of GSK2302025A (Phase 2) in terms of objective clinical responses (complete (CR) or partial (PR) response) [ Time Frame: At year 1.5 ]
  • Clinical activity of GSK2302025A (Phase 2) in terms of objective clinical responses (complete (CR) or partial (PR) response) [ Time Frame: At Year 2 ]
  • Clinical activity of GSK2302025A (Phase 2) in terms of objective clinical responses (complete (CR) or partial (PR) response) [ Time Frame: At year 2.5 ]
  • Clinical activity of GSK2302025A (Phase 2) in terms of objective clinical responses (complete (CR) or partial (PR) response) [ Time Frame: At Year 3 ]
  • Clinical activity of GSK2302025A (Phase 2) in terms of objective clinical responses (complete (CR) or partial (PR) response) [ Time Frame: At year 3.5 ]
  • Clinical activity of GSK2302025A (Phase 2) in terms of objective clinical responses (complete (CR) or partial (PR) response) [ Time Frame: At 4years + 1 month ]
  • Clinical activity of GSK2302025A (Phase 2) in terms of objective clinical responses (complete (CR) or partial (PR) response) [ Time Frame: At 6 months after the concluding visit ]
  • Clinical activity of GSK2302025A (Phase 2) in terms of objective clinical responses (complete (CR) or partial (PR) response) [ Time Frame: At 12 months after the concluding visit ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 15, 2018)
  • Number of Patients With Any Unsolicited Adverse Events (AEs), by Maximum Grading [ Time Frame: During the entire study period - up to Year 4 + 1 month post last study treatment administration ]
    An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject 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. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. The grading to be used by the investigators for the assessment of the severity of adverse events (AEs) was defined as the Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0 (Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe or medically significant; Grade 4 = life-threatening; Grade 5 = death related to AE). Adverse Events were coded to the preferred term (PT) level by means of the Medical Dictionary for Regulatory Activities (MedDRA).
  • Number of Patients With Serious Adverse Events (SAEs), by Maximum Grading [ Time Frame: During the entire study period - up to Year 4 + 1 month post last study treatment administration ]
    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. The grading to be used by the investigators for the assessment of the severity of adverse events (AEs) was defined as the Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0 (Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe or medically significant; Grade 4 = life-threatening; Grade 5 = death related to AE). SAEs were coded to the preferred term (PT) level by means of the Medical Dictionary for Regulatory Activities (MedDRA).
  • Number of Patients With Laboratory Abnormalities Versus Baseline, by Maximum Grading [ Time Frame: During the entire study period - up to Year 4 + 1 month post last study treatment administration ]
    Laboratory abnormalities belong to hematological and biochemical parameters such as: activated partial thromboplastin time prolonged [APTTP], alanine aminotransferase increased [ALT/I], alkaline phoshatase increased [APH/I], anemia [AN], asparatate aminostransferase increased [AST/I], blood bilirubin increased [BB/I], creatinine increased [CRE/I], gamma glumatymtransferase increased [GGT/I], hemoglobin increased [Hgb/I], hypoalbuminemia [HYP], lymphocyte count decreased [LYMC/D], lymphocyte count increased [LYMC/I], neutrophil count decreased [ NEUC/D], platelet count decreased [PLA/D], white blood cell decreased [WBC/D]. Parameter grades (G0,1,2,3,4,Unknown) were compared to each baseline parameter grade (GUnknown,0,1,2,3), as defined by the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009 [http://evs.nci.nih.gov/ftp1/CTCAE]. This endpoint presents values for [APTTP] grading versus baseline parameter grading.
  • Number of Patients With Laboratory Abnormal Results Versus Baseline, by Maximum Grading [ Time Frame: During the entire study period - up to Year 4 + 1 month post last study treatment administration ]
    Laboratory abnormalities belong to hematological and biochemical parameters such as: activated partial thromboplastin time prolonged [APTTP], alanine aminotransferase increased [ALT/I], alkaline phoshatase increased [APH/I], anemia [AN], asparatate aminostransferase increased [AST/I], blood bilirubin increased [BB/I], creatinine increased [CRE/I], gamma glumatymtransferase increased [GGT/I], hemoglobin increased [Hgb/I], hypoalbuminemia [HYP], lymphocyte count decreased [LYMC/D], lymphocyte count increased [LYMC/I], neutrophil count decreased [ NEUC/D], platelet count decreased [PLA/D], white blood cell decreased [WBC/D]. Parameter grades (G0,1,2,3,4,Uknown) were compared to each baseline parameter grade (GUnknown,0,1,2,3), as defined by the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009 [http://evs.nci.nih.gov/ftp1/CTCAE]. This endpoint presents values for [ALT/I] and [APH/I] grading versus baseline parameter grading.
  • Number of Patients With Hematological and Biochemical Abnormalities Versus Baseline, by Maximum Grading [ Time Frame: During the entire study period - up to Year 4 + 1 month post last study treatment administration ]
    Laboratory abnormalities belong to hematological and biochemical parameters such as: activated partial thromboplastin time prolonged [APTTP], alanine aminotransferase increased [ALT/I], alkaline phoshatase increased [APH/I], anemia [AN], asparatate aminostransferase increased [AST/I], blood bilirubin increased [BB/I], creatinine increased [CRE/I], gamma glumatymtransferase increased [GGT/I], hemoglobin increased [Hgb/I], hypoalbuminemia [HYP], lymphocyte count decreased [LYMC/D], lymphocyte count increased [LYMC/I], neutrophil count decreased [ NEUC/D], platelet count decreased [PLA/D], white blood cell decreased [WBC/D]. Parameter grades (G0,1,2,3,4,Uknown) were compared to baseline parameter grades (GUnknown,0,1,2,3), as defined by the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009 [http://evs.nci.nih.gov/ftp1/CTCAE]. This endpoint presents values for [AN], [AST/I] and [CRE/I] grading versus baseline parameter grading.
  • Number of Patients With Laboratory Hematological and Biochemical Abnormalities Versus Baseline, by Maximum Grading [ Time Frame: During the entire study period - up to Year 4 + 1 month post last study treatment administration ]
    Laboratory abnormalities belong to hematological and biochemical parameters such as: activated partial thromboplastin time prolonged [APTTP], alanine aminotransferase increased [ALT/I], alkaline phoshatase increased [APH/I], anemia [AN], asparatate aminostransferase increased [AST/I], blood bilirubin increased [BB/I], creatinine increased [CRE/I], gamma glumatymtransferase increased [GGT/I], hemoglobin increased [Hgb/I], hypoalbuminemia [HYP], lymphocyte count decreased [LYMC/D], lymphocyte count increased [LYMC/I], neutrophil count decreased [ NEUC/D], platelet count decreased [PLA/D], white blood cell decreased [WBC/D]. Parameter grades (G0,1,2,3,4,Uknown) were compared to baseline parameter grades (GUnknown,0,1,2,3), as defined by the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009 [http://evs.nci.nih.gov/ftp1/CTCAE]. This endpoint presents values for [CRE/I] and [GGT/I] grading versus baseline parameter grading.
  • Number of Patients With Lab Hematological and Biochemical Abnormalities Versus Baseline, by Maximum Grading [ Time Frame: During the entire study period - up to Year 4 + 1 month post last study treatment administration ]
    Laboratory abnormalities belong to hematological and biochemical parameters such as: activated partial thromboplastin time prolonged [APTTP], alanine aminotransferase increased [ALT/I], alkaline phoshatase increased [APH/I], anemia [AN], asparatate aminostransferase increased [AST/I], blood bilirubin increased [BB/I], creatinine increased [CRE/I], gamma glumatymtransferase increased [GGT/I], hemoglobin increased [Hgb/I], hypoalbuminemia [HYP], lymphocyte count decreased [LYMC/D], lymphocyte count increased [LYMC/I], neutrophil count decreased [ NEUC/D], platelet count decreased [PLA/D], white blood cell decreased [WBC/D]. Parameter grades (G0,1,2,3,4,Uknown) were compared to each baseline parameter grade (GUnknown,0,1,2,3), as defined by the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009 [http://evs.nci.nih.gov/ftp1/CTCAE]. This endpoint presents values for [Hgb/I] and [HYP] grading versus baseline parameter grading.
  • Number of Patients With Abnormal Hematological and Biochemical Results Versus Baseline, by Maximum Grading [ Time Frame: During the entire study period - up to Year 4 + 1 month post last study treatment administration ]
    Laboratory abnormalities belong to hematological and biochemical parameters such as: activated partial thromboplastin time prolonged [APTTP], alanine aminotransferase increased [ALT/I], alkaline phoshatase increased [APH/I], anemia [AN], asparatate aminostransferase increased [AST/I], blood bilirubin increased [BB/I], creatinine increased [CRE/I], gamma glumatymtransferase increased [GGT/I], hemoglobin increased [Hgb/I], hypoalbuminemia [HYP], lymphocyte count decreased [LYMC/D], lymphocyte count increased [LYMC/I], neutrophil count decreased [ NEUC/D], platelet count decreased [PLA/D], white blood cell decreased [WBC/D]. Parameter grades (G0,1,2,3,4,Uknown) were compared to each baseline parameter grade (GUnknown,0,1,2,3), as defined by the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009 [http://evs.nci.nih.gov/ftp1/CTCAE]. This endpoint presents values for [LYMC/D] and [LYMC/I] grading versus baseline parameter grading.
  • Number of Patients With Abnormal Hematological and Biochemical Laboratory Results Versus Baseline, by Maximum Grading [ Time Frame: During the entire study period - up to Year 4 + 1 month post last study treatment administration ]
    Laboratory abnormalities belong to hematological and biochemical parameters such as: activated partial thromboplastin time prolonged [APTTP], alanine aminotransferase increased [ALT/I], alkaline phoshatase increased [APH/I], anemia [AN], asparatate aminostransferase increased [AST/I], blood bilirubin increased [BB/I], creatinine increased [CRE/I], gamma glumatymtransferase increased [GGT/I], hemoglobin increased [Hgb/I], hypoalbuminemia [HYP], lymphocyte count decreased [LYMC/D], lymphocyte count increased [LYMC/I], neutrophil count decreased [NEUC/D], platelet count decreased [PLA/D], white blood cell decreased [WBC/D]. Parameter grades (G0,1,2,3,4,Uknown) were compared to each baseline parameter grades (GUnknown,0,1,2,3), as defined by the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009 [http://evs.nci.nih.gov/ftp1/CTCAE]. This endpoint presents values for [NEUC/D], [PLA/D] and [WBC/D] grading versus baseline parameter grading.
  • Percentage of Patients With Anti-PRAME Cellular (T-cell) Response (Phase I) [ Time Frame: Up to Data Lock Point at Week 8 ]
    Cellular response was defined as: Geometric Mean Response (GMR) above the 2.68 cut-off value and at least a four-fold increase of PRAME- specific Cluster of Differentiation (CD) 4/8 T-cells. Considering that 2 studies failed to demonstrate clinical efficacy of recombinant protein based cancer vaccines, GSK decided in 2014 to stop the development and to stop recruitment in all the ongoing clinical studies. The decision was made to end the study (i.e., stopping patient enrollment, follow-ups, sample collection and analysis of samples for research purposes). Patients still on treatment at the time of the protocol amendment were offered to continue the administration of the study treatment until the last dose or until recurrence, whichever came first, or until the patient or the investigator decided to stop the study treatment. No further active protocol visit/contact was performed except for the concluding visit at Week 199, 30 days after the last treatment administration.
  • Number of Patients With Anti-PRAME Humoral Immune Response (Phase I & II) [ Time Frame: At Weeks 0, 4, 8, 10, 12, 29, 51, 75, 99, 123, 147 and conclusion visit at 30 days post last treatment administration (Week 199) for each patient ]
    A seropositive patient was a patient whose anti-PRAME antibody concentration was greater than or equal to (≥) the assay cut-off value of 12 ELISA units per milliliter (EL.U/mL). A seronegative patient was defined as a patient whose pre-treatment antibody concentration was below (<) the cut-off value. An anti-PRAME antibody responder was defined as: For a seronegative patient: a post-treatment antibody concentration ≥ the cut-off value; For a seropositive patient: a post-treatment antibody concentration ≥ twice the pre-treatment antibody concentration.
  • Number of Patients With Stable Disease (SD), Progressive Disease (PD), Mixed Response (MR) (Phase I & II) [ Time Frame: At 30 days after the last treatment administration for each patient (Week 199) ]
    Tumor response was assessed by the Response Evaluation Criteria In Solid Tumors (RECIST), where stable disease for target lesions refers to neither enough shrinkage to qualify for complete response nor sufficient increase to qualify for progressive disease taking as references the smallest sum longest diameter (LD) since the treatment started. For non-targeted lesions it refers to persistence of one or more non-target lesions. Progressive disease is related to a clear increase of diameters of lesions taking as references the smallest diameters recorded since the treatment started OR the appearance of one or more new lesions OR both of these.
  • Number of Patients With Best Overall Response, Including Mixed Response (MxR) and Slow Progressive Disease (SPD) Criteria (Phase I & II) [ Time Frame: At 30 days after the last treatment administration for each patient (Week 199) ]
    Tumor response was assessed by the RECIST criteria, where SD for target lesions refers to neither enough shrinkage to qualify for CR nor sufficient increase to qualify for PD taking as references the smallest sum longest diameter (LD) since the treatment started. For non-targeted lesions it refers to persistence of one or more nom-target lesions. Progressive disease is related to a clear increase of diameters of lesions taking as references the smallest diameters recorded since the treatment started OR the appearance of one or more new lesions OR both of these. Mixed response is defined as at least 30% decrease in the LD occurring in at least one target lesion recorded and measured at baseline. Such response occurring in otherwise SD or PD status of the LD of target lesions were classified as "SD with target lesion regression" or "PD with target lesion regression", respectively. New lesion(s) in otherwise PR status of the LD of target lesions were "PR with new lesion".
  • Anti-Protein D Humoral Response (Phase I & II) [ Time Frame: At Week 0, 4, 8, 12, 29, 51, 75, 99, 123, 147, 30 days after the last treatment administration for each patient (Week 199), with follow-up, 3, 6, 9 and 12 months after concluding visit ]
    Analysis of immunogenicity for anti-PD antibodies was not performed, following negative results to the NCT00480025 study which assessed another study product from same technology platform. For this study, the main analysis of the dose-escalation Phase I segment was performed according to protocol when all patients enrolled in the Phase I segment had received the first 4 treatment doses and had completed Week 8. The main analysis of the Phase II segment was performed according to protocol when all patients had either completed the treatment until the end of Cycle 3 or had been withdrawn from the study treatment, with the exception of anti-PD antibody responses and PRAME-specific cellular responses which were not yet performed. All samples that had been collected but not yet tested were not tested by default, except if a scientific rationale remained relevant.
  • Anti-Cytosine Phosphate Guanosine Oligodeoxynucleotide (CpG) Humoral Response (Phase I & II) [ Time Frame: At Week 0, 4, 8, 12, 29, 51, 75, 99, 123, 147, 30 days after the last treatment administration for each patient (Week 199), with follow-up, 3, 6, 9 and 12 months after concluding visit ]
    Analysis of immunogenicity for anti-CpG antibodies was not performed, following negative results to the NCT00480025 study which assessed another study product from same technology platform. For this study, the main analysis of the dose-escalation Phase I segment was performed according to protocol when all patients enrolled in the Phase I segment had received the first 4 treatment doses and had completed Week 8. The main analysis of the Phase II segment was performed according to protocol when all patients had either completed the treatment until the end of Cycle 3 or had been withdrawn from the study treatment, with the exception of anti-CpG antibody responses and PRAME-specific cellular responses which were not yet performed. All samples that had been collected but not yet tested were not tested by default, except if a scientific rationale remained relevant.
  • Time to Treatment Failure, Progression Free Survival and Overall Survival (Phase I & II) [ Time Frame: Up to concluding visit, at Week 199 ]
    Time to treatment failure (TTF) was defined as the time from first administration of study product until the date of the last administration of the product, irrespective of the reason for study treatment discontinuation. Progression-free survival (PFS) was defined as the time from first adminsitration of study product until the date of either disease progression or death (for whatever reason), whichever comes first. Overall survival (OS) was defined as the time from first administration of study product until death.
  • Duration of Response for Patients With CR, PR and SD or SD/PR Status (Phase II) [ Time Frame: Up to concluding visit, at Week 199 ]
    This analysis was not performed following negative results to the NCT00480025 study which assessed another study product from same technology platform. For this study, the main analysis of the dose-escalation Phase I segment was performed according to protocol when all patients enrolled in the Phase I segment had received the first 4 treatment doses and had completed Week 8. The main analysis of the Phase II segment was performed according to protocol when all patients had either completed the treatment until the end of Cycle 3 or had been withdrawn from the study treatment, with the exception of anti-CpG/anti-PD antibody responses and PRAME-specific cellular responses which were not yet performed. All samples that had been collected but not yet tested were not tested by default, except if a scientific rationale remained relevant.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 22, 2010)
  • Occurrence of adverse events (AEs) and serious adverse events (SAEs), including clinically significant abnormal hematological and biochemical values, (Phase 1 and 2) [ Time Frame: During the study period until 30 days after the last treatment administration ]
  • The anti-PRAME cellular (T-cell) response (Phase 1& 2) [ Time Frame: At 10 different time points (Weeks 0, 10, 30, 52, years 1.5, 2, 3.5, 4 years + 1 month, with follow-up 6 and 12 months after concluding visit) ]
  • The anti-PRAME humoral response (Phase 1& 2) [ Time Frame: At 11 different time points (Weeks 0, 4, 10, 30, 52, years 1.5, 2, 3.5, 4 years + 1 month, with follow-up, 3 and 12 months after concluding visit) ]
  • Clinical activity GSK2302025A treatment (Phase 1&2) Occurrence of objective clinical responses (CR or PR), stable disease (SD), mixed response (MR), Time to Treatment Failure (TTF), Progression-free survival (PFS), Overall survival (OS) and the duration [ Time Frame: At 12 different time points (Weeks 12, 23, 32 and 54, years 1.5, 2, 2.5, 3, 3.5 and 4years + 1 month with follow-up 6 and 12 months after concluding visit) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of a New Vaccine Treatment for Patients With Metastatic Skin Cancer
Official Title  ICMJE Study of GSK2302025A Antigen-Specific Cancer Immunotherapeutic in Patients With Metastatic Melanoma
Brief Summary The purpose of this clinical study is to examine the safety, immunogenicity and clinical activity of the immunotherapeutic product GSK2302025A (also referred to as recPRAME + AS15 Antigen-Specific Cancer Immunotherapeutic [ASCI]) administered as a first line treatment in patients with unresectable and progressive metastatic cutaneous melanoma.
Detailed Description

In this study, patients were to receive a maximum of 24 doses of recMAGE-A3 + AS15 according to four cycles over a period of four years. An active follow-phase (up to five years after registration into the study) was planned for all patients.

This protocol summary has been impacted by protocol amendment 3, so there will no longer be an active follow-up of patients after discontinuation or completion of the study treatment. The study will end approximately 30 days after the last dose will be administered.

In addition, no more biological samples will be collected for protocol research purposes. For each biological sample already collected in the scope of this study and not tested yet, testing will not be performed by default, except if a scientific rationale remains relevant.

Sampling for safety monitoring as per protocol will continue.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Melanoma
Intervention  ICMJE Biological: Immunotherapeutic GSK2302025A, different formulations
Intramuscular administration
Other Name: PRAME ASCI
Study Arms  ICMJE
  • Experimental: GSK2302025A Cohort 1
    Male or female patients with histologically proven cutaneous melanoma received the investigational Low-Dose (LD) adjuvanted GSK2302025A immunotherapeutic vaccine, intramuscularly into the deltoid or lateral region of the thigh, with alternation on right or left side at each succeeding injection. Subjects received a total of 24 administrations in 4 cycles: 6 administrations given at 2 weeks intervals in cycle 1, 6 administrations given at 3 weeks intervals in cycle 2, 4 administrations given at 6 weeks intervals in cycle 3 and 4 administrations given at 3 months interval in cycle 4.
    Intervention: Biological: Immunotherapeutic GSK2302025A, different formulations
  • Experimental: GSK2302025A Cohort 2
    Male or female patients with histologically proven cutaneous melanoma received the investigational Middle-Dose (MD) adjuvanted GSK2302025A immunotherapeutic vaccine, intramuscularly into the deltoid or lateral region of the thigh, with alternation on right or left side at each succeeding injection. Subjects received a total of 24 administrations in 4 cycles: 6 administrations given at 2 weeks intervals in cycle 1, 6 administrations given at 3 weeks intervals in cycle 2, 4 administrations given at 6 weeks intervals in cycle 3 and 4 administrations given at 3 months interval in cycle 4.
    Intervention: Biological: Immunotherapeutic GSK2302025A, different formulations
  • Experimental: GSK2302025A Cohort 3
    Male or female patients with histologically proven cutaneous melanoma received the investigational High-Dose (HD) adjuvanted GSK2302025A immunotherapeutic vaccine, intramuscularly into the deltoid or lateral region of the thigh, with alternation on right or left side at each succeeding injection. Subjects received a total of 24 administrations in 4 cycles: 6 administrations given at 2 weeks intervals in cycle 1, 6 administrations given at 3 weeks intervals in cycle 2, 4 administrations given at 6 weeks intervals in cycle 3 and 4 administrations given at 3 months interval in cycle 4.
    Intervention: Biological: Immunotherapeutic GSK2302025A, different formulations
  • Experimental: GSK2302025A Cohort 4
    In Phase 2 of the study subjects received the optimal investigational dose-level identified in Phase 1. Patients received a treatment consisting of 24 injections of the experimental GSK2302025A immunotherapeutic.
    Intervention: Biological: Immunotherapeutic GSK2302025A, different formulations
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 27, 2014)
107
Original Estimated Enrollment  ICMJE
 (submitted: June 22, 2010)
80
Actual Study Completion Date  ICMJE December 19, 2016
Actual Primary Completion Date February 11, 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female patient with histologically proven cutaneous melanoma. Phase I segment: All melanoma patients with stage IV M1b and stage IV M1c including completely resected stage IV patients but with the exception of stage IV M1c disease with serum lactate dehydrogenase > 1.5 x Upper Limit of Normal or with involvement of the Central Nervous System.

    Phase II segment: All melanoma patients with measurable, unresectable stage III melanoma including in-transit metastasis (with (N3) or without (N2c) nodal metastasis) and stage IV M1a melanoma. The patient should have documented progressive disease within 12 weeks of registration into the trial. Patients with resected stage IV and with stage IV M1b or M1c disease cannot be included.

  2. Written informed consent for PRAME expression screening and gene profiling on resected tumor tissue and for the complete study has been obtained from the patient prior to shipment of the sample for expression testing and prior to the performance of any other protocol-specific procedure.
  3. The patient is >= 18 years old at the time of signing the first informed consent form.
  4. The patient's tumor shows expression of the PRAME antigen as determined by RT-PCR analysis or any updated technique on fresh tissue sample.
  5. Eastern Cooperative Oncology Group performance status of 0 or 1.
  6. The patient has adequate bone marrow reserve, renal, adrenal and hepatic function as assessed by standard laboratory criteria.
  7. Female patients of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as current tubal ligation, hysterectomy, ovariectomy or post-menopause.
  8. Female patients of childbearing potential may be enrolled in the study, if the patient:

    • has practiced adequate contraception for 30 days prior to the study product administration, and
    • has a negative pregnancy test on the day of administration, and
    • has agreed to continue adequate contraception during the entire treatment period and for 2 months after the completion of the study product administration series.
  9. In the view of the investigator, the patient can and will comply with all the requirements of the protocol.

Exclusion Criteria:

  1. The patient has at any time received systemic chemotherapy, (bio)-chemotherapy or CTLA-4 monoclonal antibodies for metastatic disease.
  2. The patient is scheduled to receive any other anticancer treatment, including but not limited to (bio)-chemotherapeutic or immunomodulating agents and radiotherapy.
  3. The patient has received any cancer immunotherapy containing the PRAME antigen or any cancer immunotherapy for his/her metastatic disease.
  4. The patient requires concomitant treatment (more than 7 consecutive days) with systemic corticosteroids or any other immunosuppressive agents.
  5. Use of any investigational or non-registered product (drug or vaccine) other than the study product within the 30 days preceding the first ASCI dose injection or planned use during the study period
  6. The patient has (had) previous or concomitant malignancies at other sites (including carcinoma in situ), except effectively treated non-melanoma skin cancers or carcinoma in situ of the cervix or effectively treated malignancy that has been in remission for over 5 years and is highly likely to have been cured.
  7. The patient has an allergy to any component of the study investigational product or has a history of previous allergic reactions to vaccinations.
  8. The patient has a history of confirmed adrenal dysfunction.
  9. The patient has an autoimmune disease such as, but not limited to, multiple sclerosis, lupus, and inflammatory bowel disease.
  10. The patient is known to be positive for the human immunodeficiency virus (HIV).
  11. The patient has an uncontrolled bleeding disorder.
  12. The patient has a family history of congenital or hereditary immunodeficiency.
  13. The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent or to comply with the trial procedures.
  14. The patient has other concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.
  15. For female patients: the patient is pregnant or lactating.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Czechia,   France,   Germany,   Italy,   Poland,   Russian Federation
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT01149343
Other Study ID Numbers  ICMJE 113173
2009-016636-13 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
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.
URL: https://clinicalstudydatarequest.com/Posting.aspx?ID=5107
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP