Phase II Study to Assess the Safety and Immunogenicity of recMAGE-A3+AS15 ASCI With or Without Poly IC:LC

Study Overview
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Brief Summary
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The overall purpose of this research study is to find a better way to treat melanoma. The goals of this study are: To measure the side effects of and find out how well patients tolerate the recMAGE-A3 + AS15 ASCI (MAGE-A3 ASCI) treatment with or without the Poly IC:LC To see how well the patient's immune system responds to the MAGE-A3 ASCI treatment with or without the Poly IC:LC To measure the rate of return of the patient's tumor after the MAGE-A3 ASCI treatment with or without the Poly IC:LC To measure the rate of return of the patient's tumor in two groups of patients: one group positive for the gene signature, and the other group not positive for the gene signature in their tumor after the MAGE-A3 ASCI treatment with or without the Poly IC:LC.

Detailed Description
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In the first year, participants may receive up to 8 injections given in the following order: 5 ASCI injections with or without Poly IC:LC with a 3-week interval between each. 3 ASCI injections with or without Poly IC:LC with a 3-month interval between each. During years 2 through 3, participants may receive up to 5 ASCI injections with or without Poly IC:LC given in the following order: During year 2, ASCI injections with or without Poly IC:LC will be given every 3 months for a total of up to 3 injections. During year 3, ASCI injections with or without Poly IC:LC will continue to be given every 3 months for a total of up to 2 more injections.

Official Title
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A Randomized Phase II Study to Assess the Safety and Immunogenicity of recMAGE-A3+AS15 ASCI With or Without Poly IC:LC in Patients With Resected MAGE-A3 Positive, Stage IV Melanoma

Conditions
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Melanoma

Intervention / Treatment
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* Drug: MAGE-A3 ASCI injections without Poly IC:LC
* Drug: MAGE-A3 ASCI injections with Poly IC:LC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent for the study will be obtained prior to the performance of MAGE-A3 expression screening on resected tumor tissue or any other protocol-specific procedure. Male or female patient with histologically proven and completely resected stage IV cutaneous or mucosal melanoma. In terms of the American Joint Committee on Cancer (AJCC) classification [AJCC, 2009], this means that patients with resected M1a-b-c (stage IV) disease may be enrolled. The patient must have been surgically rendered free of disease no more than 12 weeks before the randomization. Patient is equal to or greater than 18 years old at the time of signing the informed consent form. The patient's tumor shows expression of the MAGE-A3 gene, as determined by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) analysis on paraffin imbedded tumor tissue (FFPE). In all patients in whom it can be obtained, a frozen portion of the resected tumor will be analyzed for gene profiling. The patient has fully recovered from surgery. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at the time of randomization. The patient must have adequate bone-marrow reserve, adequate renal function and adequate hepatic function as assessed by standard laboratory criteria: Absolute neutrophil count (ANC) equal to or greater than 1.5 x 10^9/L, Platelet count equal to or greater than 75 x 10^9/L, Serum creatinine equal to or less than 1.5 times the Upper Limit of Normal (ULN), Total bilirubin equal to or less than 1.5 times the ULN, Transaminase (ALT - AST) equal to or less than 2.5 times the ULN 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. Men must also agree to use an adequate method of contraception. In the opinion of the investigator, the patient can and will comply with all the requirements of the protocol. Exclusion Criteria: The patient has an ocular melanoma. The patient has in-transit metastases. The patient has been treated or is scheduled to be treated with an adjuvant anticancer therapy after the metastasectomy that qualifies the patient for inclusion in the present trial. One prior systemic treatment with an immunomodulator (i.e., interferon, vaccine and/or anti-CTLA-4) after a previous surgery is permitted, provided that the last dose has been administered at least 45 days before randomization in the present trial. Previous radiotherapy is permitted, provided that the treatment has been completed before the surgery that qualifies the patient for participation in the present trial. 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 is permitted. 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. 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. The patient has a family history of congenital or hereditary immunodeficiency. The patient is known to be positive for Human Immunodeficiency Virus (HIV) or has another confirmed or suspected immunosuppressive or immunodeficient condition. History of allergic disease or reactions likely to be exacerbated by any component of the treatments. 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. The patient has 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 uncontrolled bleeding disorder. For female patients: the patient is pregnant or lactating.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A: recMAGE-A3 + AS15<br>ASCI injections without Poly IC:LC | Drug: MAGE-A3 ASCI injections without Poly IC:LC<br>* MAGE-A3 ASCI injections without Poly IC:LC as outlined in Detailed Description<br>* Other names: AS15 adjuvant;|
| Active Comparator: B: recMAGE-A3 + AS15 + Poly IC:LC<br>ASCI injections with Poly IC:LC | Drug: MAGE-A3 ASCI injections with Poly IC:LC<br>* MAGE-A3 ASCI injections with Poly IC:LC as outlined in Detailed Description<br>* Other names: NSC 301463;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events Related to Study Treatment | Number of participants with adverse events after receiving one dose of recMAGE-A3 + AS15 ASCI or recMAGEA3 + AS15 ASCI in combination with Poly IC:LC | Beginning of Treatment to End of Follow Up - up to 5 years per participant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity Per Treatment Arm | Laboratory Endpoint: Assessment of the immunogenicity of the two regimens. Serum antibodies (such as Anti-MAGE-A3) seropositivity status (a seropositive patient is a patient whose titre is greater than or equal to the cut-off value) will be the primary immune endpoints assessed. Seropositivity will be assessed at baseline, after 2, 4, 6, 7 and 9 administrations, post-treatment (i.e., at concluding visit) and one year after concluding visit (i.e., at follow-up visit 2). | Beginning of Treatment to End of Follow Up - up to 5 years per participant | 
| Percentage of Participants With Relapse-Free Survival (RFS) | RFS, defined as the time from randomization to the date of first relapse of melanoma or of death, whichever comes first. Percentage of participants with RFS, assessed up to 2 years is reported | Beginning of Treatment to End of Follow Up - up to 2 years per participant | 
| Median Overall Survival (OS) | OS defined as the interval from randomization to the date of death, irrespective of the cause of death; patients still alive will be censored at the date of the last assessment. The primary analysis will be based on the adjusted Cox regression model. | At 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Resected, Skin, Stage IV