Clinical trial NCT00896480: Study of GSK2132231A Antigen-Specific Cancer Immunotherapeutic in Patients With Inoperable Metastatic Cutaneous Melanoma
Official title: Clinical Activity, Safety and Immunogenic Properties of Cancer Immunotherapeutic GSK2132231A in Patients With Unresectable and Progressive Metastatic Cutaneous Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Melanoma
Keywords: ASCI (Antigen-Specific Cancer Immunotherapeutic)
MAGE-A3
Malignant melanoma
Cancer immunotherapeutic
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2009-05-11
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The clinical objective of this clinical trial is to examine the clinical activity in terms of tumor response and time to treatment failure of the immunotherapeutic product GSK2132231A when given to patients with unresectable and progressive metastatic cutaneous melanoma. The safety of the treatment will also be assessed just as its immunogenicity in terms of the humoral and cellular immune response induced by the GSK2132231A immunotherapeutic. Translational research objectives are to assess the effects of the study treatment in terms of various biological variables.


Eligibility criteria: Inclusion Criteria:

1. The patient (male or female) has histologically proven, measurable metastatic cutaneous melanoma in one of the following stages according to the American Joint Committee on Cancer classification of 2002:

   * Stage III in transit, or
   * Stage III unresectable, or
   * Stage IV M1a.
2. There has been documented progression of the patient's disease within the 12 weeks before the first administration of study treatment.
3. The patient presents at screening with at least 3 tumor lesions of diameter \>= 0.5 mm.
4. Written informed consent has been obtained from the patient before the performance of any protocol-specific procedure.
5. The patient is \>= 18 years of age at the time of signature of informed consent.
6. The patient's tumor shows expression of MAGE-A3 gene in at least one of the two tumor biopsies performed at baseline.
7. The patient's ECOG performance status is 0 or 1.
8. The patient has normal organ functions, as assessed by standard laboratory criteria.
9. If the patient is female, she must be of non-childbearing potential, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to administration of study treatment, have a negative pregnancy test and continue such precautions during the entire study treatment period and for 2 months after completion of the treatment injection series.
10. In the view of the investigator, the patient can and will comply with the requirements of the protocol.

Exclusion Criteria:

1. The patient has at any time received systemic (bio)-chemotherapy
2. The patient is scheduled to receive any anti-cancer specific treatment, including radiotherapy, immunotherapy, chemotherapy and immunomodulating agents.
3. The patient requires concomitant treatment with systemic corticosteroids, or any other immunosuppressive agents.
4. The patient has received any cancer immunotherapeutic containing a MAGE A3 antigen or any cancer immunotherapeutic for his/her metastatic disease.
5. Use of any investigational or non-registered product (drug or vaccine) other than the study treatment within the 30 days preceding the first dose of study treatment, or planned use during the study period.
6. The patient has (or has had) previous or concomitant malignancies at other sites, except effectively treated malignancy that is considered by the investigator highly likely to have been cured.
7. History of allergic disease or reactions likely to be exacerbated by any component of the study investigational product.
8. The patient has an autoimmune disease such as, but not limited to, neuroinflammatory autoimmune diseases, systemic lupus erythematosus, and inflammatory bowel disease
9. The patient has a family history of congenital or hereditary immunodeficiency.
10. The patient is known to be positive for the human immunodeficiency virus (HIV).
11. The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent, or to comply with the study procedures.
12. 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.
13. For female patients: the patient is pregnant or lactating.

Primary outcomes:
measure: Number of Patients With Objective Tumor Response (OR) to GSK2132231A Study Treatment
timeFrame: From Pre-treatment (up to 4 weeks before first treatment) to study end (Year 4), each patient being censored out of the analysis at 1st report of disease progression in assessed lesions
measure: Number of Patients With Mixed Response (MR) to GSK2132231A
timeFrame: From Pre-treatment (up to 4 weeks before first treatment) to study end (Year 4), each patient being censored out of the analysis at 1st report of disease progression in assessed lesions
measure: Time to Treatment Failure (TTF), by Gene Signature
timeFrame: From Pre-treatment (up to 4 weeks before first treatment) to study end (Year 4), each patient being censored out of the analysis at 1st report of disease progression or death
measure: Anti-MAGE-A3 Antibody Concentrations
timeFrame: From Pre-treatment (up to 4 weeks before first treatment) to Concluding visit (CCL: at Week 196 + 30 to 37 days for patients completing the treatment, 1 month after the last Dose administered for patients withdrawn from study treatment before completion)
measure: Number of Seroconverted Patients for Anti-MAGE-A3
timeFrame: From Pre-treatment (up to 4 weeks before first treatment) to Concluding visit (CCL: at Week 196 + 30 to 37 days for patients completing the treatment, 1 month after the last Dose administered for patients withdrawn from study treatment before completion)
measure: Number of Patients With Treatment Response for Anti-MAGE-A3 Antibodies
timeFrame: From Day 2 to Concluding visit (CCL:at Week 196 + 30 to 37 days for patients completing the treatment, 1 month after the last Dose administered for patients withdrawn from study treatment before completion)
measure: Geometric Mean Titers of Anti-MAGE-A3 Specific CD4+ and CD8+ T-cells Concentrations After Immunization
timeFrame: From Pre-treatment (up to 4 weeks before first treatment) to Concluding visit (CCL: at Week 196 + 30 to 37 days for patients completing the treatment, 1 month after the last Dose administered for patients withdrawn from study treatment before completion)
measure: Number of Patients With CD4+ and CD8+ T Cell Frequency ≥ 1.24 Cut-off
timeFrame: From Pre-treatment (up to 4 weeks before first treatment) to Concluding visit (CCL: at Week 196 + 30 to 37 days for patients completing the treatment, 1 month after the last Dose administered for patients withdrawn from study treatment before completion)
measure: Number of Patients With a Cellular Response (Anti-MAGE-A3 Specific CD4+ and CD8+ T-cells Concentrations After Immunization)
timeFrame: From Week 5 to Concluding visit (CCL: at Week 196 + 30 to 37 days for patients completing the treatment, 1 month after the last Dose administered for patients withdrawn from study treatment before completion)
measure: Number of Patients Reported With Antigen Specific Cancer Immunotherapeutics (ASCI)-Related grade3/4 Adverse Events (AEs) According to the Common Terminology Criteria (CTCAE) Version 3.0.
timeFrame: Within the 31-day (Days 0-30) post-administration periods
measure: Number of Patients Reported With Serious Adverse Events (SAEs)
timeFrame: During the entire study period (from Day 0 to CCL: at Week 196 + 30 to 37 days for patients completing the treatment, 1 month after the last Dose administered for patients withdrawn from study treatment before completion
measure: Number of Patients With Abnormal Alanine Aminotransferase (ALT) Values by Maximum Grade
timeFrame: From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
measure: Number of Patients With Abnormal Aspartate Aminotransferase (AST) Values by Maximum Grade
timeFrame: From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
measure: Number of Patients With Abnormal Alkaline Phosphatase (ALK) Values by Maximum Grade
timeFrame: From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
measure: Number of Patients With Abnormal Bilirubine (BIL) Values by Maximum Grade
timeFrame: From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
measure: Number of Patients With Abnormal Creatinine (CREA) Values by Maximum Grade
timeFrame: From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
measure: Number of Patients With Abnormal Gamma-glutamyl Transpeptidase (GGT) Values by Maximum Grade
timeFrame: From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
measure: Number of Patients With Abnormal Hemoglobin (HGB) Values by Maximum Grade
timeFrame: From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
measure: Number of Patients With Abnormal Hypercalcemia (HCA) Values by Maximum Grade
timeFrame: From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
measure: Number of Patients With Abnormal Hyperkalemia (HKA) Values by Maximum Grade
timeFrame: From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
measure: Number of Patients With Abnormal Hypernatremia (HNA) Values by Maximum Grade
timeFrame: From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
measure: Number of Patients With Abnormal Hypoalbuminemia (hAL) Values by Maximum Grade
timeFrame: From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
measure: Number of Patients With Abnormal Hypocalcemia (hCA) Values by Maximum Grade
timeFrame: From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
measure: Number of Patients With Abnormal Hypokalemia (hKA) Values by Maximum Grade
timeFrame: From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
measure: Number of Patients With Abnormal Hyponatremia (hNA) Values by Maximum Grade
timeFrame: From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
measure: Number of Patients With Abnormal Leukocytes (LEU) Values by Maximum Grade
timeFrame: From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
measure: Number of Patients With Abnormal Lymphopenia (LYM) Values by Maximum Grade
timeFrame: From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
measure: Number of Patients With Abnormal Neutrophils (NEU) Values by Maximum Grade
timeFrame: From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
measure: Number of Patients With Abnormal Platelets (PLT) Values by Maximum Grade
timeFrame: From Screening and up to Week 11 (Cycle 1), Week 30 (Cycle 2), Week 52 (Cycle 3), and Study End at Year 4 (Cycle 4)
measure: Number of Patients With Any Adverse Events (AEs) and With AEs by Maximum Grade
timeFrame: Within the 31-day (Day 0-30) follow-up period post treatment administration.
measure: Number of Patients With Any AE(s) and With AEs by Maximum Grade, Related to Treatment Administration
timeFrame: Within the 31-day (Day 0-30) follow-up period post treatment administration.
measure: Number of Patients With Any Serious Adverse Events (SAEs) and With SAEs by Maximum Grade
timeFrame: Within the 31-day (Day 0-30) follow-up period post treatment administration.
measure: Number of Patients With Any Serious Adverse Events (SAEs) and With SAEs by Maximum Grade, Related to Treatment Administration
timeFrame: Within the 31-day (Day 0-30) follow-up period post treatment administration.
Secondary outcomes:
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: GSK Investigational Site
city: Brussel
country: Belgium
facility: GSK Investigational Site
city: Wilrijk
country: Belgium
facility: GSK Investigational Site
city: Caen
country: France
facility: GSK Investigational Site
city: Lille
country: France
facility: GSK Investigational Site
city: Paris Cedex 10
country: France
facility: GSK Investigational Site
city: Reims
country: France
facility: GSK Investigational Site
city: Villejuif
country: France
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Baurain JF, Robert C, Mortier L, Neyns B, Grange F, Lebbe C, Ulloa-Montoya F, De Sousa Alves PM, Gillet M, Louahed J, Jarnjak S, Lehmann FF. Association of homogeneous inflamed gene signature with a better outcome in patients with metastatic melanoma treated with MAGE-A3 immunotherapeutic. ESMO Open. 2018 Jul 25;3(5):e000384. doi: 10.1136/esmoopen-2018-000384. eCollection 2018.