Patients with unresectable and progressive metastatic cutaneous melanoma, whose tumor expresses MAGE-A3. MedDRA version: 20.0 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 100000004864
Conditions
Sponsors
GlaxoSmithKline Biologicals
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patient with histologically proven, measurable metastatic cutaneous melanoma. According to the American Joint Committee on Cancer 2002 classification, all melanoma patients with stage IV M1b and stage IV M1c with serum lactate dehydrogenase (LDH) = 18 years of age at the time of signature of the Informed Consent. 4. The patient’s tumor shows expression of MAGE-A3 antigen, detected by Reverse-Transcription Polymerase Chain Reaction (RT-PCR). A tumor biopsy performed in the context of institution standard practice or another research study may be used for the MAGE-A3 testing (or the use of the result of the MAGE-A3 testing) provided this biopsy was preserved in RNAlater, was taken no more than 12 weeks before the first administration of study treatment and after obtention of the Sponsor’s agreement. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 6. The patient has normal organ functions 7. 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. 8. In the view of the investigator, the patient can and will comply with all the study procedures Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
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 the first study treatment administration). 2. 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. 3. The patient requires concomitant treatment with systemic corticosteroids, or any other immunosuppressive agents. The use of prednisone, or equivalent, < 0.125 mg/kg/day (absolute maximum 10 mg/day), or inhaled corticosteroids for chronic obstructive pulmonary disease (COPD), or topical steroids is permitted. 4. The patient 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 8 weeks before the first study treatment administration. 5. The patient has received any investigational or non-registered drug or vaccine other than the study medication within the 30 days preceding the first dose of study treatment, or plans to receive such a drug 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, multiple sclerosis, lupus, and inflammatory bowel disease. Patients with vitiligo are not excluded. 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 trial 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. 14. The patient has an uncontrolled bleeding disorder
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Co-primary objectives of this study are to characterize in the overall population and in the gene signature subsets: • To assess the safety of recMAGE-A3 + AS15 in association with dacarbazine in patients with MAGE-A3-positive metastatic cutaneous melanoma, with emphasis on any possible toxic effects. • To assess the specific humoral and cellular immune response induced by the recMAGE-A3 + AS15 in association with dacarbazine in patients with MAGE-A3-positive metastatic cutaneous melanoma. ;Secondary Objective: The secondary objectives of this study are to characterize in the overall population and in the gene signature subsets • To assess the clinical activity of recMAGE-A3 + AS15 in association with dacarbazine in patients with MAGE-A3-positive metastatic cutaneous melanoma. • To assess other indicators of safety. ;Primary end point(s): The two co-primary endpoints are: • Safety of the ASCI injections assessed in terms of the: – Occurrence of ASCI-related grade 3/4 adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. – Occurrence of serious adverse events during the study. • Immunogenicity will be judged primarily after the fourth dose of ASCI: – The anti-MAGE-A3 seroconversion and concentration. – The anti-protein D seroconversion and concentration. – The MAGE-A3 cellular (T-cell) response. ;Timepoint(s) of evaluation of this end point: Occurrence of ASCI-related grade 3/4 adverse events: After the concluding visit of the last patient Occurrence of serious adverse events during the study: After the concluding visit/contact of the last patient Immunogenicity:At regular intervals during the treatment period (9 assessments per patient) and after the concluding visit of the last patient | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoints are to measure: -The rate of objective response (complete and partial) -The rate of stable disease -The rate of mixed response -Time to study treatment failure -Progression free survival time -Progression free survival time after initial Slow Progressive Disease -Occurrence of any adverse events (including abnormal laboratory values for haematology and biochemistry) -Overall survival;Timepoint(s) of evaluation of this end point: -The rate of objective response: After the concluding visit of the last patient -The rate of stable disease: After the concluding visit/contact of the last patient -The rate of mixed response: After the concluding visit/contact of the last patient -Time to study treatment failure: After the concluding visit/contact of the last patient -Progression free survival time: After the concluding visit/contact of the last patient -Progression free survival time after initial Slow Progressive Disease: -After the concluding visit/contact of the last patient -Occurrence of any adverse events: After the concluding visit of the last patient -Overall survival: After the concluding visit / contact of the last patient | — |
Countries
Belgium, France
Contacts
Public ContactClinical Disclosure Advisor
GlaxoSmithKline Biologicals
Outcome results
None listed