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
- 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
- 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
- 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
- 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
- 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.
- 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
- 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
- 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
- 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 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
- 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.