Patients with histologically proven stage IIIB or IIIC cutaneous melanoma with macroscopic lymph node involvement suitable for surgical resection. Macroscopic lymph node involvement is defined as clinically detectable lymph node metastases confirmed by pathological examination following therapeutic lymphadenectomy MedDRA version: 14.1 Level: PT Classification code 10025670 Term: Malignant melanoma stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts a
Conditions
Sponsors
GlaxoSmithKline Biologicals
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Written informed consent for MAGE-A3 expression screening and gene expression profiling on resected tumor tissue has been obtained from the patient prior to shipment of the sample for expression testing and gene expression profiling, and written informed consent for the complete study has been obtained prior to the performance of any other protocol-specific procedure. 2.Male or female patient with histologically proven stage IIIB or IIIC cutaneous melanoma presenting with macroscopic lymph node involvement suitable for surgery. In terms of the AJCC classification, this means that patients with T1-4a N1-2b M0 (stage IIIB with macroscopic nodal involvement) and patients with T1-4b N1-2bM0 or any TN3 macroscopic M0 (>= 4 macroscopic nodes or macroscopic matted nodes) may be enrolled. Macroscopic lymph-node involvement is defined as clinically detectable lymph node metastases confirmed by pathological examination following therapeutic lymphadenectomy (including nodal metastasis exhibiting gross extracapsular extension). Clinical detection includes the diagnosis by any imaging technique or physical examination and gross lymph node examination by a pathologist. Patients with unknown primaries are eligible for the study. 3.The patient must have been surgically rendered free of disease no more than 9 weeks before the randomization. For patients undergoing an elective dissection followed by a lymphadenectomy, the date of the radical lymphadenectomy is considered the day when the patient is free of disease and will be taken as the reference point to count the 9-week interval. In the case where a first surgery does not render the patient free of disease a second surgery may be performed. The patient will still be eligible if a complete lymphadenectomy of the same lymphatic basin is performed. 4.Patient is >= 18 years old at the time of signing the informed consent form. 5.The patient’s lymph node tumor shows expression of the MAGE-A3 gene, as determined by RT-PCR analysis on formalin-fixed paraffin-embedded (FFPE) tissue. 6.The patient has fully recovered from surgery. 7.ECOG performance status of 0 or 1 at the time of randomization. 8.The patient must have adequate bone-marrow reserve, adequate renal function and adequate hepatic function as assessed by standard laboratory criteria. 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 randomization, have a negative pregnancy test and continue such precautions during the entire study treatment period and for 2 months after completion of the injection series. 10.In the opinion of the investigator, the patient can and will comply with all 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 910 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 390
Exclusion criteria
Exclusion criteria: 1.The patient suffers from a mucosal or ocular melanoma. 2.The patient has or has had any history of in-transit metastases(N2c or N3). 3.The patient has been treated or is scheduled to be treated with an adjuvant anti-cancer therapy except for the following: •Prior systemic treatment with an immunomodulator (i.e., interferon and/or anti-CTL-A4) following a previous surgery, provided that a wash-out period of 30 days before randomization in the present trial is respected. •Previous radiotherapy, provided that the treatment has been completed before the lymphadenectomy that qualifies the patient for participation in the present trial 4.The patient requires concomitant chronic treatment (more than 7 consecutive days) with systemic corticosteroids or any other immunosuppressive agents. The use of prednisone, or equivalent, at a dose of < 0.125 mg/kg/day (absolute maximum 10 mg/day) or topical steroids and inhaled corticosteroids is permitted. 5.Use of any investigational or non-registered product (drug or vaccine) other than the study treatment within 30 days preceding the randomization or planned use during the study period. 6.The patient has a history of autoimmune disease such as, but not limited to, multiple sclerosis, lupus, and inflammatory bowel disease. Patients with vitiligo are not excluded. 7.The patient has a family history of congenital or hereditary immunodeficiency. 8.The patient is known to be positive for Human Immunodeficiency Virus (HIV) or has another confirmed or suspected immunosuppressive or immunodeficient condition. 9.History of allergic disease or reactions likely to be exacerbated by any component of the treatments. 10.The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent or to comply with the trial procedures. 11.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. 12.The patient has previous or concomitant malignancies at other sites (including carcinoma in situ but not melanoma in situ), 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. 13.The patient has an uncontrolled bleeding disorder. 14.For female patients: the patient is pregnant or lactating.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Disease Free Survival: Once the pre-defined number of events is reached;Main Objective: -To demonstrate the clinical efficacy in terms of disease-free survival (DFS) of the recMAGE-A3 + AS15 ASCI compared to placebo in the overall population of patients with completely resected stage III melanoma with macroscopic lymph node involvement -To demonstrate the clinical efficacy in terms of DFS of the recMAGE-A3 + AS15 ASCI compared to placebo in the population presenting the potentially favourable gene expression signature. ;Secondary Objective: To evaluate DFS in the population of patients who do not present he potentially favorable gene signature (GS); To evaluate overall survival in the overall and GS (sub-)populations; To evaluate the disease-free specific survival in the overall and GS (sub-)populations; To evaluate the distant metastasis-free survival in in the overall and GS (sub-)populations; To evaluate the 1-year, 2-year, 3-year and 4-year DFS rates in the overall and GS (sub-)populations; To validate the predictive value of the GS by evaluating the association between treatment outcome (DFS) and GS status; To evaluate the ASCI wrt safety and other clinical and biological indicators of efficacy in in the overall and GS (sub-)populations; To evaluate the immune response to the ASCI in in the overall and GS (sub-)populations; To evaluate and compare the changes in health-related quality of life in patients treated with recMAGE-A3 + AS15 ASCI to those treated with placebo using the EuroQoL-5D questionnaire.;Primary end point(s): The primary endpoint is Disease Free Survival (DFS), defined as the time from randomization to either the date of first recurrence of the disease or the date of death (whatever the cause), whichever occurs first. •Types of recurrence to be considered as an event include loco-regional and distant metastases. •In addition, any death occurring without prior documentation of tumor recurrence will b | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Overall Survival •Disease-free specific survival •Distant metastasis-free survival •Anti-MAGE-A3 and anti-protein D seropositivity status •Occurrence of adverse events including abnormal haematological and biochemical parameters. •Occurrence of serious adverse events and autoimmunity events •Health-related quality of life (utility) assessment using the EuroQoL 5D (EQ-5D) questionnaire.;Timepoint(s) of evaluation of this end point: •Overall Survival : At the time of analysis •Disease-free specific survival : At the time of analysis •Distant metastasis-free survival : At the time of analysis •Anti-MAGE-A3 and anti-protein D seropositivity status: Post-treatment and 1 year after concluding visit •Occurrence of adverse events including abnormal haematological and biochemical parameters.: Up to 30 days after each study dose. •Occurrence of serious adverse events and autoimmunity events: During the whole study duration up to 30 days after the last administration of study treatment •Health-related quality of life (utility) assessment using the EuroQoL 5D (EQ-5D) questionnaire : At regular intervals from Visit 1 (baseline) till 6 months after the concluding visit or 1 year post-recurrence | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Czech Republic, Estonia, France, Germany, Greece, Ireland, Israel, Italy, Japan, Korea, Democratic People's Republic of, Mexico, Netherlands, Norway, Poland, Romania, Russian Federation, Serbia, Spain, Sweden, Switzerland, Taiwan, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Disclosure Advisor
GlaxoSmithkline Biologicals Belgium
Outcome results
None listed