Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed With Surgery

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. PURPOSE: This randomized phase II trial is studying two different regimens of vaccine therapy and comparing them to see how well they work in treating patients with stage III or stage IV melanoma that cannot be removed with surgery.

Detailed Description
-----------------
OBJECTIVES: Primary Compare the objective response rate (complete and partial response) in patients with unresectable stage III or stage IV M1a cutaneous melanoma immunized with vaccine comprising D1/3-MAGE-3-His fusion protein and SB-AS02B adjuvant vs SB-AS15 adjuvant. Compare the activity of SB-AS02B adjuvant vs SB-AS15 adjuvant, in terms of maximizing the antigenicity of MAGE-3, in patients treated with these regimens. Compare the rate of grade 3/4 vaccine-related toxicity in patients treated with these regimens. Secondary Compare progression-free survival in patients treated with these regimens. OUTLINE: This is a randomized, open label, parallell-group, multicenter study. Patients are stratified according to disease stage (III in transit vs other stage III vs IV), presence of lesion ≥ 20 mm (yes vs no), and participating center. Patients are randomized to 1 of 2 treatment arms. Induction therapy Arm I: Patients receive immunization comprising D1/3-MAGE-3-His fusion protein and SB-AS02B adjuvant intramuscularly (IM) once weekly on weeks 1, 3, 5, 7, 9, and 11. Arm II: Patients receive immunization comprising D1/3-MAGE-3-His fusion protein SB-AS15 adjuvant IM once weekly on weeks 1, 3, 5, 7, 9, and 11. Patients achieving a clinical complete response (CR), partial response (PR), stable disease (SD), or slow progressive disease (SPD) proceed to maintenance therapy. Maintenance therapy: Patients in both arms receive immunization (according to their randomized arm) once weekly on weeks 15, 18, 21, 24, 27, 30, 34, 40, 46, and 52. Patients maintaining a CR, PR, or SD proceed to long-term treatment. Long-term treatment: Beginning 3 months after completion of maintenance therapy, patients in both arms receive immunization (according to their randomized arm) once every 3 months for 4 courses and then once every 6 months for 4 courses. Treatment continues in both arms in the absence of disease progression that does not correspond to SPD status, unacceptable toxicity, or the diagnosis of an autoimmune disease. Patients are followed every 12 weeks. PROJECTED ACCRUAL: A total of 68 patients (34 patients per treatment arm) will be accrued for this study.

Official Title
-----------------
Randomized, Open Phase II Study of Immunization With the Recombinant MAGE-3 Protein Combined With Adjuvant AS02B or AS15 in Patients With Unresectable and Progressive Metastatic Cutaneous Melanoma

Conditions
-----------------
Melanoma (Skin)

Intervention / Treatment
-----------------
* Biological: D1/3-MAGE-3-His fusion protein
* Biological: SB-AS02B adjuvant
* Biological: SB-AS15 adjuvant


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed cutaneous melanoma Unresectable stage III OR stage IV M1a disease Documented progressive disease within the past 12 weeks Measurable disease Skin, soft tissue, or lymph node metastasis allowed provided the disease is not amenable to curative treatment with surgery Tumor must express the MAGE-3 gene by reverse transcription polymerase chain reaction analysis (more than 1% of the positive MAGE-3 control included in the assay) No visceral metastases within the past 56 days by imaging PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-1 Life expectancy Not specified Hematopoietic Hemoglobin ≥ lower limit of normal (LLN) WBC ≥ LLN Lymphocyte count ≥ LLN Platelet count ≥ LLN No bleeding disorders Hepatic Bilirubin ≤ upper limit of normal (ULN) Lactic dehydrogenase ≤ ULN AST and ALT ≤ 2 times ULN PT and aPTT normal Hepatitis B surface antigen negative (antibody test may be positive) Hepatitis C antibody negative Renal Creatinine ≤ ULN Cardiovascular No clinically significant heart disease (CTC grade III or IV) Immunologic No autoimmune disease (vitiligo allowed) No anti-nuclear antibody titer ≥ 1/320 OR equal to 1/160 AND auto-antibodies directed against specific auto-antigens No immunodeficiency No active infection requiring antibiotic therapy HIV negative Other Not pregnant Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after study participation No other malignancy within the past 5 years except surgically cured basal cell or squamous cell skin cancer or carcinoma in situ of the cervix No other serious acute or chronic illness requiring concurrent medications No psychological, familial, sociological, or geographical condition that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy More than 8 weeks since prior adjuvant vaccine therapy No prior vaccine therapy containing a MAGE-3 antigen No prior vaccine therapy for metastatic melanoma No concurrent immunomodulating agents (e.g., BCG) Chemotherapy No prior systemic chemotherapy No concurrent chemotherapy Endocrine therapy No concurrent corticosteroids Concurrent prednisone or equivalent allowed provided the dose is ≤ 40 mg/day and treatment duration is for no more than 3 weeks Concurrent inhaled and topical steroids are allowed Radiotherapy No prior radiotherapy to the spleen No concurrent radiotherapy to > 20% of all existing lesions (i.e., target lesions, non-target lesions, and nonmeasurable lesions) Concurrent local low-dose (≤ 20 Grays) radiotherapy allowed Surgery Recovered from prior surgery or biopsy No prior organ allograft No prior splenectomy Concurrent surgery to a limited number of lesions allowed for patients with a complete response, partial response, or stable disease after at least 3 courses of study therapy Other No prior systemic anticancer therapy More than 4 weeks since prior isolated limb perfusion therapy No other concurrent anticancer therapy No other concurrent immunosuppressive agents

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: D1/3-MAGE-3-His fusion protein|nan|
|Biological: SB-AS02B adjuvant|nan|
|Biological: SB-AS15 adjuvant|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate (complete response and partial response) as assessed by RECIST criteria |  |  | 
| Vaccine-related toxicity as assessed by CTCAE v3 |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of stabilization as assessed by RECIST criteria |  |  | 
| Rate of mixed response as assessed by RECIST criteria |  |  | 
| Rate of immune response |  |  | 
| Progression-free survival |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage III melanoma, stage IV melanoma, recurrent melanoma