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

NCT01213472 | Completed Phase 1 Results

• 2 other identifiers: 1124062010-020663-20
• Study Type: interventional
• Target: 33
• Locations: 7 countries
• Sites: 22

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.

Conditions

Melanoma

Keywords

ASCI; melanoma; tumor antigen; unresectable; progressive; NY-ESO-1; adult; cancer-testis antigen; Immunotherapy

Outcome Measures

Primary Outcomes (3)

• Number of Patients With Severe Toxicities During the Study Treatment Period

  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.

  During the study treatment period (maximum duration = 49 months).

• Number of Patients With Severe Toxicities During the Follow-up Period

  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.

  During the one year follow-up period (i.e. from Month 49 until Month 61)

• Number of Patients With the Best Overall Response in the Overall Population

  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.

  During the study treatment period (maximum duration = 49 months).

Secondary Outcomes (15)

• Number of Patients With Best Overall Response Including Mixed Response (MxR) and Slow Progressive Disease (SPD) Criteria

  During the study treatment period (maximum duration = 49 months).

• 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

  After 12, 22, 31 and 54 weeks of treatment.

• Number of Patients With Adverse Events (AEs) by Maximum Grade

  During the study treatment period (maximum duration = 49 months).

• Number of Patients With Adverse Events (AEs) That Are Causally Related to Treatment Administration by Maximum Grade

  During the study treatment period (maximum duration = 49 months).

• Number of Patients With Serious Adverse Events (SAEs) by Maximum Grade

  During the study treatment period (maximum duration = 49 months).

Study Arms (1)

NY-ESO 1 Group

EXPERIMENTAL

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)

Interventions

GSK Biologicals' 2241658A Antigen-Specific Cancer Immunotherapeutic (ASCI) BIOLOGICAL

Up to 24 intramuscular administrations

NY-ESO 1 Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (24)

GSK Investigational Site

North Sydney, New South Wales, 2060, Australia

Location

GSK Investigational Site

Woolloongabba, Queensland, 4102, Australia

Location

GSK Investigational Site

Graz, A-8036, Austria

Location

GSK Investigational Site

Marseille, 13385, France

Location

GSK Investigational Site

Montpellier, 34295, France

Location

GSK Investigational Site

Nantes, 44093, France

Location

GSK Investigational Site

Paris, 75006, France

Location

GSK Investigational Site

Freiburg im Breisgau, Baden-Wurttemberg, 79104, Germany

Location

GSK Investigational Site

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

GSK Investigational Site

Hanover, Lower Saxony, 30625, Germany

Location

GSK Investigational Site

Lübeck, Schleswig-Holstein, 23538, Germany

Location

GSK Investigational Site

Genoa, Liguria, 16132, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20132, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20133, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20141, Italy

Location

GSK Investigational Site

Siena, Tuscany, 53100, Italy

Location

GSK Investigational Site

Amsterdam, 1081 HV, Netherlands

Location

GSK Investigational Site

Maastricht, 6229 HX, Netherlands

Location

GSK Investigational Site

Rotterdam, 3075 EA, Netherlands

Location

GSK Investigational Site

Geneva, 1211, Switzerland

Location

GSK Investigational Site

Zurich, 8091, Switzerland

Location

GSK Investigational Site

Chelmsford, CM1 7ET, United Kingdom

Location

GSK Investigational Site

Leicester, LE1 5WW, United Kingdom

Location

GSK Investigational Site

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (1)

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

  BACKGROUND

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: GSK Clinical Trials
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

877-379-3718

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2010
• First Posted: October 4, 2010
• Study Start: January 31, 2011
• Primary Completion: April 17, 2018
• Study Completion: April 17, 2018
• Last Updated: October 9, 2019
• Results First Posted: October 9, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

FR (4); AU (1); NL (3); GB (3); DE (4); CH (2); IT (5)