Adult patients with histologically proven, measurable metastatic cutaneous melanoma (stage III in transit or unresectable, or stage IV M1a), with documented progressive disease within the 12 weeks before the first administration of study treatment
Conditions
Sponsors
GlaxoSmithKline Biologicals
Eligibility
Sex/Gender
All
Inclusion 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 three 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 9. If the patient is female, she must be of non-childbearing potential, i.e. have a current tubal ligation, hysterectomy, ovariectomy or be post-menopausal, 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 all study treatment period and for 2 months after completion of the treatment administration series. 10. In the view of the investigator, the patient can and will comply with the requirements of the protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. The patient has at any time received systemic (bio-)chemotherapy (except for isolated limb perfusion, as long as this was performed at least 4 weeks before first study treatment administration). 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. [Note: The use of prednisone, or equivalent, <0.5 mg/kg/day (absolute maximum 40 mg/day), or inhaled corticosteroids for chronic obstructive pulmonary disease or topical steroids is permitted and does not count as fulfilment of this exclusion criterion.] 4. The patient has received any cancer immunotherapeutic containing a MAGE-A3 antigen or any cancer immunotherapeutic for his/her metastatic disease. [Note: Previous adjuvant treatment with a cancer immunotherapeutic containing a tumor antigen other than MAGE-A3 is allowed if the last administration took place at least eight weeks before the first ASCI administration in the present study.] 5. Use of any investigational or non-registered product (drug or vaccine) other than the study treatment(s) 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. [Patients with vitiligo are not excluded by this criterion.] 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The clinical objectives of this study are to characterize in patients with MAGE-A3-positive metastatic cutaneous melanoma: 1. The clinical activity of the study treatment in terms of objective response, stable disease and mixed response. 2. The clinical activity of the study treatment recMAGE A3 + AS15 in terms of time to treatment failure. 3. The safety of the study treatment The immunological objectivesof the trial are to document the humoral and cellular immune response induced by the study treatment recMAGE A3 + AS15.;Secondary Objective: The objectives of the translational research are globally to assess the effects of the study treatment in terms of various biological variables. In detail: • To explore epitope spreading in the peripheral blood induced by the study treatment, • To explore the evolution of regulatory T cells in the peripheral blood during immunisation by the study treatment, • To profile by genetic (microarray) and proteomics evaluations the immunological response to the study treatment, • To explore the cross-talk between the patient’s immune system and tumor before and under the study treatment • To evaluate the concomitant expression of tumor antigen expression (MAGE A3, MAGE C2, NY ESO 1, LAGE-1, WT1 and PRAME) and of any potential gene profile expression and their evolution during immunization ;Primary end point(s): Endpoints for assessment of clinical activity are: 1. Tumor response (objective response, stable disease, mixed response) 2. Time to treatment failure (patient withdrawn from study treatment) The safety of the study treatment will be assessed in terms of: 1. Occurrence of ASCI related grade 3/4 adverse events 2. Occurrence of serious adverse events during the study 3. Documentation of any toxicity observed Endpoints for assessment of immunogenicity are: 1. Anti-MAGE-A3 seroconversion 2. Anti-MAGE-A3 antibody concentration 3. The MAGE-A3 cellular (T-cell) CD4 and CD8 response | — |
Countries
Belgium, France
Outcome results
None listed