Phase II Study to Assess the Safety and Immunogenicity of recMAGE-A3+AS15 ASCI With or Without Poly IC:LC
Condition: Melanoma
MeSH terms: Melanoma
Intervention: MAGE-A3 ASCI injections without Poly IC:LC; MAGE-A3 ASCI injections with Poly IC:LC
Intervention description: MAGE-A3 ASCI injections without Poly IC:LC as outlined in Detailed Description; MAGE-A3 ASCI injections with Poly IC:LC as outlined in Detailed Description
Intervention MeSH terms: Poly I-C
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Resected; Skin; Stage IV

Summary:

      The overall purpose of this research study is to find a better way to treat melanoma.

      The goals of this study are:

        1. 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

        2. To see how well the patient's immune system responds to the MAGE-A3 ASCI treatment with
           or without the Poly IC:LC

        3. To measure the rate of return of the patient's tumor after the MAGE-A3 ASCI treatment
           with or without the Poly IC:LC

        4. 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.
    

Eligibility criteria:

        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.