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Evaluation of a New Anti-cancer Immunotherapy in Patients With Non-operable and Progressing Metastatic Cutaneous Melanoma

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: NCT01213472
Recruitment Status : Completed
First Posted : October 4, 2010
Results First Posted : October 9, 2019
Last Update Posted : October 9, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
The purpose of this study is to investigate the safety, immunogenicity and clinical activity of GSK2241658A antigen-specific cancer immunotherapeutic (ASCI) for the treatment of patients with non-operable and progressing metastatic cutaneous melanoma.

Condition or disease Intervention/treatment Phase
Melanoma Biological: GSK Biologicals' 2241658A Antigen-Specific Cancer Immunotherapeutic (ASCI) Phase 1

Detailed Description:

In this study, patients were to receive a maximum of 24 doses of recNY-ESO-1 + AS15 ASCI according 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.

As of Amendment 3, there will no longer be an active follow-up of patients after discontinuation or completion of the treatment. The study will end 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.

Blood sampling for safety monitoring as per protocol will continue.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 33 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Study of GSK2241658A Antigen-Specific Cancer Immunotherapeutic in Patients With Unresectable and Progressive Metastatic Cutaneous Melanoma
Actual Study Start Date : January 31, 2011
Actual Primary Completion Date : April 17, 2018
Actual Study Completion Date : April 17, 2018

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: NY-ESO 1 Group
Patients with non-operable and progressing metastatic cutaneous melanoma, received up to 24 doses of GSK2241658A Cancer Immunotherapeutic, provided that at each tumor evaluation time point, the clinical criteria to continue the treatment were met, including patients having a clinical response.
Biological: GSK Biologicals' 2241658A Antigen-Specific Cancer Immunotherapeutic (ASCI)
Up to 24 intramuscular administrations




Primary Outcome Measures :
  1. Number of Patients With Severe Toxicities During the Study Treatment Period [ Time Frame: During the study treatment period (maximum duration = 49 months). ]
    Severe toxicity was defined, according to the Common Terminology Criteria for Adverse Events (CTCAE) (version 4.0), as 1)an Antigen-Specific Cancer Immunotherapeutic (ASCI) related or possibly related Grade 3 or higher toxicity. Grade 3 myalgia, arthralgia, headache, fever, rigors/chills and fatigue (including lethargy, malaise and asthenia) should persist for 48 hours despite therapy to be taken into account and as 2)an ASCI related or possibly related Grade 2 or higher allergic reaction occurring within 24 hours of the dose administration.

  2. Number of Patients With Severe Toxicities During the Follow-up Period [ Time Frame: During the one year follow-up period (i.e. from Month 49 until Month 61) ]
    Severe toxicity was defined, according to the Common Terminology Criteria for Adverse Events (CTCAE) (version 4.0), as 1)an Antigen-Specific Cancer Immunotherapeutic (ASCI) related or possibly related Grade 3 or higher toxicity. Grade 3 myalgia, arthralgia, headache, fever, rigors/chills and fatigue (including lethargy, malaise and asthenia) should persist for 48 hours despite therapy in order to be taken into account and as 2)an ASCI related or possibly related Grade 2 or higher allergic reaction occurring within 24 hours of the dose administration. All active follow-up visits and procedures were stopped, hence this follow-up analysis was not performed as initially planned.

  3. Number of Patients With the Best Overall Response in the Overall Population [ Time Frame: During the study treatment period (maximum duration = 49 months). ]
    Best response was recorded from the start of treatment until disease progression. Response assessment was essentially based on a set of measurable lesions (target lesions [TL]), and any other lesions (non-target lesions [NTL]), both identified at baseline. Complete Response (CR)=disappearance of all TL or NTL; Partial Response (PR) = at least 30 percent (%) decrease in the sum of the longest diameter(LD) of TL compared to baseline, stable disease (SD) = neither sufficient shrinkage to qualify PR nor sufficient increase to qualify for Progressive disease (PD) compared with baseline; PD = at least 20% increase in the sum of LD of TL compared with baseline, or the appearance of one or more new lesions, or both of these, and/or unequivocal progression of existing NTL; NE =non-evaluable; Clinical response: any CR or PR best overall response; Disease control: any CR, PR, SD or SD/PR best overall response.


Secondary Outcome Measures :
  1. Number of Patients With Best Overall Response Including Mixed Response (MxR) and Slow Progressive Disease (SPD) Criteria [ Time Frame: During the study treatment period (maximum duration = 49 months). ]
    Patients with Slow Progressive Disease (SPD) status met the following criteria: patient's Eastern Cooperative Oncology Group (ECOG) performance status was 0 or 1, patient's lactate dehydrogenase (LDH) value was not greater than twice the normal upper limit, there was no appearance of visceral metastases other than in the lung, patients did not meet any of the criteria for permanent stopping of study treatment. Mixed response (MxR) criteria was defined as follows: at least 30% decrease in the longest diameter (LD) occurring in at least one target lesion recorded and measured at baseline. Such response occurring in otherwise stable disease (SD) or progressive disease (PD) status of LD of target lesions and without the appearance of one or more new lesions were classified as "SD with target lesion regression" or "PD with target lesion regression". The appearance of new lesions in otherwise partial response (PR) status of the LD of target lesions were classified as "PR with new lesion".

  2. Number of Patients With Objective Clinical Response (CR or PR) in the Population of Patients Who Present the Predictive Melanoma Antigen A3 (MAGE-A3) Gene Signature [ Time Frame: After 12, 22, 31 and 54 weeks of treatment. ]
    Following MAGE3-AS15-NSC-003 (ADJ) (NCT00480025) study (A double-blind, randomized, placebo-controlled Phase III study to assess the efficacy of recMAGE-A3 + AS15 Antigen-Specific Cancer immunotherapeutic as adjuvant therapy in patients with resected MAGE-A3-positive Non-Small Cell Lung Cancer) showed the absence of treatment effect in any of the primary, secondary, or exploratory analyses, clinical activity was not reported within the population of patients who present the predictive MAGE-A3 gene signature, in that study.

  3. Number of Patients With Adverse Events (AEs) by Maximum Grade [ Time Frame: During the study treatment period (maximum duration = 49 months). ]
    An AE is any untoward medical occurrence in a clinical investigation patient, temporally associated with the use of a medical product, whether or not considered related to the medicinal product. An AE can be any unfavorable 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 efficacy), abuse or misuse.

  4. Number of Patients With Adverse Events (AEs) That Are Causally Related to Treatment Administration by Maximum Grade [ Time Frame: During the study treatment period (maximum duration = 49 months). ]
    An AE is any untoward medical occurrence in a clinical investigation patient, temporally associated with the use of a medical product, whether or not considered related to the medicinal product. An AE can be any unfavorable 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 efficacy), abuse or misuse.

  5. Number of Patients With Serious Adverse Events (SAEs) by Maximum Grade [ Time Frame: During the study treatment period (maximum duration = 49 months). ]
    A serious adverse event (SAE) is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study patient, is a grade 4 AE according to the Common Terminology Criteria for Adverse Events (CTCAE, v 4.0), in addition, in this study, Grade 3 or higher pIMDs were considered as medically significant and were therefore notified as SAE.

  6. Number of Patients With Serious Adverse Events (SAEs) That Are Causally Related to Treatment Administration by Maximum Grade [ Time Frame: During the study treatment period (maximum duration = 49 months). ]
    A serious adverse event (SAE) is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study patient, is a grade 4 AE according to the Common Terminology Criteria for Adverse Events (CTCAE, v 4.0), in addition, in this study, Grade 3 or higher pIMDs will be considered as medically significant and will therefore be notified as SAE. No serious adverse events were reported during the study period that are causally related to treatment administration by maximum grade.

  7. Time to Treatment Failure (TTF) [ Time Frame: From first treatment administration (i.e. at Week 0) until the last treatment administration (i.e. at Month 48) ]
    Time to Treatment Failure (TTF) was defined as the time from first treatment until the date of the last treatment administration, for patients who discontinued the treatment prematurely, regardless of the reason for study treatment discontinuation. Patients who completed their full treatment phase or who were still on treatment at the time of analysis were censored on their last study treatment administration date..

  8. Progression-free Survival (PFS) Rate [ Time Frame: From first treatment administration (i.e. at Week 0) until the last tumor evaluation (i.e. at Month 49) ]
    Progression-free survival (PFS) was defined as the time from first treatment to either the date of first disease progression (PD) or the date of death (for whatever reason), whichever came first. Patients alive and without disease progression were censored at the date of the last visit/contact.

  9. Overall Survival (OS) [ Time Frame: From first treatment administration (i.e. at Week 0) until the last tumor evaluation (i.e. at Month 49) ]
    Overall survival (OS) was defined as the time from first treatment until death. Patients alive at the time of analysis were censored at the time of last visit/contact.

  10. The Duration of Response for Patients With CR, PR or Stable Disease (SD) Status [ Time Frame: From first treatment administration (i.e. at Week 0) until the last tumor evaluation (i.e. at Month 49) ]
    The duration of response was measured from the time when the measurement criteria for CR/PR (whichever was recorded first) or SD evaluation were met until the first date that first PD or death was objectively documented (taking as reference for PD the smallest measurements recorded since the treatment started). Stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the sum of LD of target lesions recorded previously but not necessarily at baseline (The minimal time interval required between two measurements for determination of SD was at least 16 weeks.). The analysis was not performed as initially planned.

  11. Number of Patients With Progression-free Survival Events [ Time Frame: From first treatment administration (i.e. at Week 0) until the last tumor evaluation (i.e. at Month 49) ]
    Progression-free survival was defined as the time from the date of registration of the patient to either the date of disease progression or the date of death (for whatever reason), whichever came first. Patients alive and without disease progression were censored at the date of their last tumor evaluation. PFS events included progressive disease (PD), death in absence of PD and events (Any event which was part of the natural course of the disease under study, was captured as an efficacy measure. Therefore it did not need to be reported as an SAE).

  12. Summary of Deaths Related to Progressive Disease of Cancer Under Study Reported After the Study Treatment, in the Period of Long-term Follow-up for Survival [ Time Frame: During the long-term Follow-Up period for progressive disease and survival [1 year after the study treatment end (at Month 49) or up to 5 years after the first study treatment administration, regardless of disease progression and study discontinuation.] ]
    Summary of deaths included death, autopsy performed and cause of death. Progression of the tumor was recorded in the clinical assessments. Death due to progressive disease was to be recorded on a specific form in the case report form but not as a serious adverse event (SAE). However, if the investigator considered that there was a causal relationship between the administration of the treatment or protocol design/procedures and the disease progression, then this must be reported as an SAE.

  13. Anti NY-ESO-1 Antibody Concentrations [ Time Frame: Before treatment (PRE), at 4 (W4), 8 (W8), 10 (W10), 12 (W12), 29 (W29), 51 (W51), 75 (W75), 99 (W99), 123 (W123) weeks of treatment and at the concluding visit, i.e. at Month 49 (POST) ]
    Anti-NY-ESO-1 antibody concentrations were presented as geometric mean concentrations (GMTs) and expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).

  14. Humoral Response for Anti NY-ESO-1 Antibodies [ Time Frame: At 4 (W4), 8 (W8), 10 (W10), 12 (W12), 29 (W29), 51 (W51), 75 (W75), 99 (W99), 123 (W123) weeks of treatment and at the concluding visit, i.e. at Month 49 (POST) ]
    Anti NY-ESO-1 antibody response was defined as: For initially seronegative patients: post-vaccination antibody concentration greater than or equal to (≥) 179 EU/mL and for intially seropositive patients: post-vaccination antibody concentration ≥ 2 fold the pre-vaccination antibody concentration.

  15. Cell Mediated Immune Response for Anti-NY-ESO-1 Antibodies (T-cell) [ Time Frame: Before treatment (PRE), at 4 (W4), 8 (W8), 10 (W10), 12 (W12), 29 (W29), 51 (W51), 75 (W75), 99 (W99), 123 (W123) weeks of treatment and at the concluding visit, i.e. at Month 49 (POST) ]
    Cellular (T-cell) response was not analysed as data only available for few patients.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patient with histologically proven, measurable metastatic cutaneous melanoma, and with documented progressive disease within the 12 weeks before the first administration of study treatment.
  • Written informed consent for NY-ESO-1 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.
  • Patient is >= 18 years of age at the time of signature of the informed consent.
  • The patient's tumor shows expression of NY-ESO-1, as determined by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis or any updated technique on fresh tissue sample(s).
  • Eastern Cooperative Oncology Group performance status of 0 or 1.
  • The patient has normal organ functions as shown by all of the following:

    • Hemoglobin ≥ 12 g/dL
    • Absolute leukocytes count ≥ 3.0 x 1000000000/L
    • Absolute lymphocytes count ≥ 1.0 x 1000000000/L
    • Platelets ≥ 100 x 1000000000/L
    • Serum creatinine ≤ Upper Limit of Normal (ULN)
    • Serum total bilirubin ≤ 1.5 x ULN (except for patients with Gilbert's syndrome for whom the limit is 2 x ULN)
    • Lactate dehydrogenase ≤ ULN
    • Aspartate aminotransferase ≤ 2 × ULN
    • Alanine aminotransferase ≤ 2 × ULN

These tests must be done no more than 3 weeks before the first ASCI administration.

  • Female patients of non-childbearing potential may be enrolled in the study.
  • Female patient of childbearing potential may be enrolled in the study, if the patient:

    • has practiced adequate contraception for 30 days prior to first ASCI administration, and
    • has a negative pregnancy test at the specified study visits, and
    • has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the ASCI administration series.
  • In the view of the investigator, the patient can and will comply with the requirements of this protocol.

Exclusion Criteria:

  • The patient has at any time received systemic chemotherapy, biochemotherapy, small molecules or nti-CTLA-4 monoclonal antibody for metastatic disease.
  • The patient is scheduled to receive any other anticancer treatments than those specified in the protocol, including but not limited to (bio-) chemotherapeutic, immunomodulating agents and radiotherapy.
  • The patient received any cancer immunotherapy containing a NY-ESO-1 antigen or any cancer immunotherapy for his/her metastatic disease.
  • The patient requires concomitant treatment with systemic corticosteroids, or any other immunosuppressive agents.
  • Use of any investigational or non-registered product other than the ASCI within 30 days preceding the first ASCI administration, or planned use during the study period.
  • The patient has (had) previous or concomitant malignancies at other sites, 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.
  • The patient has an allergy to any component of the study investigational product or has a history of previous allergic reactions to vaccinations.
  • The patient has an autoimmune disease such as, but not limited to, multiple sclerosis, lupus, and inflammatory bowel disease. Patients with vitiligo are not excluded.
  • The patient has a family history of congenital or hereditary immunodeficiency.
  • The patient is known to be positive for the Human Immunodeficiency Virus.
  • The patient has an uncontrolled bleeding disorder.
  • The patient has a family history of congenital or hereditary immunodeficiency.
  • The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent, or to comply with the trial 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01213472


Locations
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Australia, New South Wales
GSK Investigational Site
North Sydney, New South Wales, Australia, 2060
Australia, Queensland
GSK Investigational Site
Woolloongabba, Queensland, Australia, 4102
Austria
GSK Investigational Site
Graz, Austria, A-8036
France
GSK Investigational Site
Marseille Cedex 5, France, 13385
GSK Investigational Site
Montpellier cedex 5, France, 34295
GSK Investigational Site
Nantes Cedex 1, France, 44093
GSK Investigational Site
Paris, France, 75006
Germany
GSK Investigational Site
Freiburg, Baden-Wuerttemberg, Germany, 79104
GSK Investigational Site
Heidelberg, Baden-Wuerttemberg, Germany, 69120
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30625
GSK Investigational Site
Luebeck, Schleswig-Holstein, Germany, 23538
Italy
GSK Investigational Site
Genova, Liguria, Italy, 16132
GSK Investigational Site
Milano, Lombardia, Italy, 20132
GSK Investigational Site
Milano, Lombardia, Italy, 20133
GSK Investigational Site
Milano, Lombardia, Italy, 20141
GSK Investigational Site
Siena, Toscana, Italy, 53100
Netherlands
GSK Investigational Site
Amsterdam, Netherlands, 1081 HV
GSK Investigational Site
Maastricht, Netherlands, 6229 HX
GSK Investigational Site
Rotterdam, Netherlands, 3075 EA
Switzerland
GSK Investigational Site
Genève, Switzerland, 1211
GSK Investigational Site
Zürich, Switzerland, 8091
United Kingdom
GSK Investigational Site
Chelmsford, United Kingdom, CM1 7ET
GSK Investigational Site
Leicester, United Kingdom, LE1 5WW
GSK Investigational Site
Southampton, United Kingdom, SO16 6YD
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
  Study Documents (Full-Text)

Documents provided by GlaxoSmithKline:
Study Protocol  [PDF] September 3, 2014
Statistical Analysis Plan  [PDF] April 5, 2018

Publications:
American Joint Committee on Cancer. 2002. Cancer staging manual. Sixth edition. Springer editions.

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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01213472    
Other Study ID Numbers: 112406
2010-020663-20 ( EudraCT Number )
First Posted: October 4, 2010    Key Record Dates
Results First Posted: October 9, 2019
Last Update Posted: October 9, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
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
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
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: http://clinicalstudydatarequest.com
Keywords provided by GlaxoSmithKline:
ASCI
melanoma
tumor antigen
unresectable
progressive
NY-ESO-1
adult
cancer-testis antigen
Immunotherapy
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas