Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Melanoma, Cutaneous Malignant

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Antineoplastic Agents

Imidazole

Immunomodulating Agents

Dacarbazine

Antineoplastic Agents, Alkylating

Alkylating Agents

Enzyme Inhibitors

All patients are to receive the same treatment consisting of 24 injections of the immunotherapeutic GSK2132231A combined with a course of 8 cycles of dacarbazine given at the beginning of the treatment

Immunotherapeutic GSK2132231A

GSK Clinical Trials

The purpose of this clinical trial is to find out how successfully, patients with progressive metastatic cutaneous melanoma, are able to develop an immune response to injections with the immunotherapeutic product GSK1572932A when given in combination with dacarbazine and evaluate the safety of this combination.

This Protocol Posting has been updated following amendment 3, dated 16 October 2009. The sections impacted are :

* Enrollment, number of subjects
* Outcome measures
* Exclusion criteria

A Study of Safety and Clinical Activity of Immunotherapy Plus Chemotherapy in Metastatic Melanoma Patients

Study of GSK2132231A Antigen-Specific Cancer Immunotherapeutic in Association With Chemotherapy in Patients With Unresectable and Progressive Metastatic Cutaneous Melanoma

The assessed AEs were ASCI-related grade 3/4 adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. An unsolicited AE covers any untoward medical occurrence in a clinical investigation patient temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Related = AE assessed by the investigator as related to the treatment.

Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Events which were part of the natural course of the disease under study (i.e., disease progression, recurrence) were captured as part of the clinical activity outcome variables in this study; therefore these did not need to be reported as SAEs. Progression/recurrence of the tumor in a patient was recorded as part of the clinical assessment data collection, and deaths due to progressive disease was recorded on a specific form, but not as an SAE. However, if the investigator considered that there was a causal relationship between treatment or protocol design/procedures and the disease progression/recurrence, then the event was reported as an SAE. Any new primary cancer (non-related to the cancer under study) was reported as an SAE.

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.

Anti-MAGE-A3 antibody concentrations were presented as geometric mean concentrations (GMTs) and expressed in ELISA units per millilitre (EL.U/mL)

Treatment response defined as: For initially seronegative patients: post-administration antibody concentration ≥ 27 EL.U/mL For initially seropositive patients: post-administration antibody concentration ≥ 2 fold the pre-vaccination antibody concentration

Anti-PD antibody concentrations were presented ad geometric mean concentrations (GMTs) and expressed in ELISA units per millilitre (EL.U/mL).

Treatment response defined as: For initially seronegative patients: post-administration antibody concentration ≥ 100 EL.U/mL For initially seropositive patients: post-administration antibody concentration ≥ 2 fold the pre-vaccination antibody concentration

Analysis of MAGE-A3 cellular response was not performed and data were not collected..

Response assessment was done based on a set of measurable lesions (MLs) identified at baseline as target lesions (TLs), and followed up until disease progression. Up to 5 MLs per organ \& 10 in total were identified as TLs and measured at baseline, selected based on size (those with the longest diameter \[LD\]) and measurability; a sum of LDs for all TLs was calculated and reported as baseline sum LD, which was used to characterize objective tumor response (OR), OR being defined as either complete response (CR) and/or partial response (PR) post MAGE-A3 ASCI treatment. After identification, MLs and TLs were assessed as regards CR and PR definitions per Response Evaluation Criteria in Solid Tumors (RECIST) criteria: CR = Disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to \<10 mm in short axis; PR = At least a 30% decrease in the SLD of target lesions, taking as reference the baseline sum diameters.

Assessment was done based on a set of MLs identified at baseline as TLs and NTLs followed up until disease progression. TLs and NTLs were assessed as regards matching or not SD-related definitions, 1) SD definitions per Response Evaluation Criteria in Solid Tumors (RECIST) criteria for TLs \>= 20 mm and TLs both \>= and \< 20 mm: a) for TLs: SD = Neither sufficient shrinkage to qualify as a PR nor sufficient increase to qualify as PD, taking as references the smallest sum LD since treatment start. and b) for NTLs: SD = Persistence of one or more NTL; 2) following below criteria for TLs \< 20mm e. a. a) for TLs: PR/SD = Neither sufficient shrinkage to qualify for CR nor sufficient increase, to qualify for PD taking as references the smallest sum LD since treatment start, and b) for NTLs: PR/SD = Persistence of one or more NTL.

Assessment was done based on a set of MLs identified at baseline as TLs and NTLs followed up until disease progression. Stable disease was defined as follows: 1) In case of target lesions (TL) greater than or equal to (≥) 20 mm: neither sufficient shrinkage to qualify for Partial Response nor sufficient increase to qualify for Progressive Disease, taking as references the sum of Longest Diameter (LD) of TL recorded previously but not necessarily at baseline; 2) In case of TL both less than 20 mm and ≥ 20 mm: Neither sufficient shrinkage to qualify as a PR nor sufficient increase to qualify as PD, taking as references the smallest sum LD since the start of the treatment. The minimal time interval required between 2 measurements for determination of SD was at least 12 weeks.

Assessment was done based on a set of MLs identified at baseline as TLs and NTLs followed up until disease progression. MLs were assessed as regards matching below MxR definitions. In case of evaluability per RECIST: a) MxR Type 1= at least (a.l.) 30% decrease in LD in a.l. one TL measured at baseline. Such response occurring in SD/PD status of LD of TL and without appearance of one or more new lesions = SD/PD with TL regression; b) MxR Type 2: appearance of one or more new lesions occurring in SD/PR status of LD of TL, and = SD/PR with new lesion. In case of non-evaluability per RECIST: a) MxR Type 1 = a clear decrease in diameters occurring in a.l. one TL measured at baseline. Such response occurring in SD/PD status of LD of (baseline) TL and without appearance of one or more new lesions = SD/PD with TL regression; b) MxR Type 2 = appearance of one or more new lesions occurring in SD/PR status of LD of TL = SD/PR with new lesion.

TTF was defined as withdrawal from treatment with the MAGE-A3 ASCI study product due to disease progression or death. TTF analysis was performed using the non-parametric Kaplan-Meier method.

PFS was defined and calculated as the time from first treatment to either the first progression of the disease or the date of death, whichever occurred first. In case a patient went off protocol treatment, the date of first documented progression (if applicable) was to be used as date of progression. Patients still alive with no evidence of disease progression at the time of their last visit or for whom date of first documented progression was not applicable, were censored at the time of the last examination. PFS analysis was performed using the non-parametric Kaplan-Meier method.

PFS after initial SPD was defined and calculated as the time from the time point at which the disease was the most advanced during the treatment to either a new progression of the disease or the date to death, whichever occurred first as another secondary outcome of this study. In that case, the largest diameter during the course of treatment was to be used as reference measurement. This outcome was defined to take into account the delay to induce an active immune response and the strict rules set up in this study to allow pursuing investigational treatment in case of SPD. PFS after SPD analysis was performed using the non-parametric Kaplan-Meier method.

OS was defined as the time from first treatment to the date of death. OS analysis was performed using the non-parametric Kaplan-Meier method. Each patient was censored out at the time of death.

The status of each patient as regards ALT laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0), G1 and G2. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).

The status of each patient as regards AST laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).

The status of each patient as regards ALK laboratory values at baseline (SCR) up to study end(SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).

The status of each patient as regards BIL laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Unknown (UNK) and Grade 0 (G0). CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).

The status of each patient as regards CREA laboratory values at baseline (SCR) up to study end(SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0). CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).

The status of each patient as regards GGT laboratory values at baseline (SCR) up to study end(SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0), G1 and G3. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).

The status of each patient as regards HGB laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).

The status of each patient as regards HCA laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Unknown (UNK), Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).

The status of each patient as regards HKA laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0), G1 and G2. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).

The status of each patient as regards HNA laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).

The status of each patient as regards hAL laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Unknown (UNK), Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).

The status of each patient as regards hCA laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Unknown (UNK), Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).

The status of each patient as regards hKA laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).

The status of each patient as regards hNA laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).

The status of each patient as regards LEU laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).

The status of each patient as regards LYM laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).

The status of each patient as regards NEU laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0). CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).

The status of each patient as regards PTT laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).

The status of each patient as regards PLT laboratory values at baseline (SCR) up to study end (SE) was collected and graded according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. The post-treatment values were presented by worst grade versus baseline grade. SCR CTC grade statuses reported were Grade 0 (G0) and G1. CTC grade statuses reported at SE were G0, G1, G2, G3, G4, and Unknown (UNK).

An AE was any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs reported are here below tabulated irrespective of grade (any), as well as graded by maximum grade reported according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. Maximum grade reported and tabulated were Grade 1 (G1), G2, G3, G4 and G5.

SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a patient, is a Grade 4 AE according to the CTCAE, version3.0. Events which were part of the natural course of the disease under study were captured as part of the clinical activity outcome variables in this study; therefore did not need to be reported as SAEs. Progression/recurrence of the tumor was recorded as part of the clinical assessment data collection, and deaths due to progressive disease was recorded on a specific form, but not as an SAE. SAEs reported are here below tabulated irrespective of grade (any), as well as graded by maximum grade reported according to the Common Terminology Criteria (CTC) Adverse event terminology, version 3.0. Maximum grade reported and tabulated were Grade 1 (G1), G2, G3, G4 and G5.

GlaxoSmithKline

The occurrence of reported AEs (all/related) was not available and is encoded as equal to the number of subjects affected.

Patients planned to receive intramuscularly up to 24 doses of GSK2132231A, in 4 cycles.

GSK2132231A GROUP

Subset of patients with the pre-specified gene signature, receiving the GSK2132231A product. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening.

GSK2132231A GS+ Group

Subset of patients without the pre-specified gene signature, receiving the GSK2132231A product. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening.

GSK2132231A GS- Group

Subset of patients with unknown status as regards GS signature, receiving the GSK2132231A product. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening.

GSK2132231A GS Unknown Group

Total

Age, Continuous

Sex: Female, Male

GSK Response Center

Any event, Grade 3

Any event, Grade 4

Any Blood and lymphatic system disorders, Grade 3

Any Blood and lymphatic system disorders, Grade 4

Anaemia, Grade 3

Anaemia, Grade 4

Lymphopenia, Grade 3

Lymphopenia, Grade 4

Neutropenia, Grade 3

Neutropenia, Grade 4

Thrombocytopenia, Grade 3

Thrombocytopenia, Grade 4

Any Cardiac disorders, Grade 3

Any Cardiac disorders, Grade 4

Tachycardia, Grade 3

Tachycardia, Grade 4

Any Gastrointestinal disorders, Grade 3

Any Gastrointestinal disorders, Grade 4

Constipation, Grade 3

Constipation, Grade 4

Diarrhoea, Grade 3

Diarrhoea, Grade 4

Dyspepsia, Grade 3

Dyspepsia, Grade 4

Nausea, Grade 3

Nausea, Grade 4

Paraesthesia oral, Grade 3

Paraesthesia oral, Grade 4

Vomiting, Grade 3

Vomiting, Grade 4

Any Gen. disord. and adm. site conditions, Grade 3

Any Gen. disord. and adm. site conditions, Grade 4

Asthenia, Grade 3

Asthenia, Grade 4

Chills, Grade 3

Chills, Grade 4

Fatigue, Grade 3

Fatigue, Grade 4

Influenza like illness, Grade 3

Influenza like illness, Grade 4

Injection site erythema, Grade 3

Injection site erythema, Grade 4

Injection site inflammation, Grade 3

Injection site inflammation, Grade 4

Injection site oedema, Grade 3

Injection site oedema, Grade 4

Injection site pain, Grade 3

Injection site pain, Grade 4

Injection site reaction, Grade 3

Injection site reaction, Grade 4

Mucosal dryness, Grade 3

Mucosal dryness, Grade 4

Oedema peripheral, Grade 3

Oedema peripheral, Grade 4

Pyrexia, Grade 3

Pyrexia, Grade 4

Any Investigations, Grade 3

Any Investigations, Grade 4

Haemoglobin decreased, Grade 3

Haemoglobin decreased, Grade 4

Any Metabolism and nutrition disorders, Grade 3

Any Metabolism and nutrition disorders, Grade 4

Decreased appetite, Grade 3

Decreased appetite, Grade 4

Any Musculoskeletal and conn. Tiss. Diso., Grade 3

Any Musculoskeletal and conn. Tiss. Diso., Grade 4

Arthralgia, Grade 3

Arthralgia, Grade 4

Myalgia, Grade 3

Myalgia, Grade 4

Pain in extremity, Grade 3

Pain in extremity, Grade 4

Any Nervous system disorders, Grade 3

Any Nervous system disorders, Grade 4

Burning sensation, Grade 3

Burning sensation, Grade 4

Headache, Grade 3

Headache, Grade 4

Paraesthesia, Grade 3

Paraesthesia, Grade 4

Presyncope, Grade 3

Presyncope, Grade 4

Any Psychiatric disorders, Grade 3

Any Psychiatric disorders, Grade 4

Insomnia, Grade 3

Insomnia, Grade 4

Any Resp., thoracic and mediastinal. dis., Grade 3

Any Resp., thoracic and mediastinal. dis., Grade 4

Rhinitis allergic, Grade 3

Rhinitis allergic, Grade 4

Any Skin and subcutaneous tissue disorder, Grade 3

Any Skin and subcutaneous tissue disorder, Grade 4

Alopecia, Grade 3

Alopecia, Grade 4

Eczema, Grade 3

Eczema, Grade 4

Photosensitivity reaction, Grade 3

Photosensitivity reaction, Grade 4

Pruritus, Grade 3

Pruritus, Grade 4

The Total Treated population included all patients who have received at least one dose of the GSK2132231A product.

Number of Patients Reported With Unsolicited Adverse Events (AEs) That Were Causally Related to Treatment Administration by Maximum Grade.

Number of Patients Reported With Serious Adverse Events (SAEs)

Number of Seroconverted Patients for Melanoma Antigen (Anti-MAGE-A3)

Subset of patients with unknown status as regards GS signature, receiving the GSK2132231A product. Gene-signature sub-grouping was based on patients having a potentially predictive gene signature, as assessed at screening

The ATP population for Immunogenecity included all eligible patients, who have received at least the first 4 GSK2132231A doses concomitantly to the standard chemotherapy regimen and provided a valid result for immunogenecity measurement within the 4 weeks following the 4th dose.

Spots Global Cancer Trial Database for A Study of Safety and Clinical Activity of Immunotherapy Plus Chemotherapy in Metastatic Melanoma Patients

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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