Immunotherapy of HLA-A2 Positive Stage III/IV Melanoma Patients

Study Overview
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Brief Summary
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The purpose of this study is to determine whether vaccination with tumor antigenic peptides and both CpG and Montanide adjuvants can induce an immune response in melanoma patients and to assess the safety of this vaccination.

Detailed Description
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Immune therapy with tumor antigenic peptides is generally quite well tolerated. However, immune activation is often only weak or even undetectable, and clinical responses (supposedly corresponding to protective immunity) are unfortunately infrequent. Further progress is required to improve the vaccines, with the goal to increase the strength of immune activation. The tumor antigenic peptides Melan-A/Mart-1 (EAA and ELA) and Tyrosinase (YMD) are combined with two drugs in this study, both of which are known to enhance immune responses: first, CpG 7909 oligodeoxynucleotides, and second, Montanide ISA-51. Group 1: vaccination with Melan-A analog peptide + CpG and Montanide adjuvants; Group 2: vaccination with Melan-A natural peptide + CpG and Montanide adjuvants; Group 3 : vaccination with Melan-A natural and Tyrosinase peptides + CpG and Montanide adjuvants; Group 4 : vaccination with Melan-A analog and Tyrosinase peptides + CpG and Montanide adjuvants.

Official Title
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Immunotherapy of HLA-A2 Positive Stage III/IV Melanoma Patients With CpG7909, Tumor Antigenic Peptides and Montanide

Conditions
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Melanoma

Intervention / Treatment
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* Biological: group 1
* Biological: group 2
* Biological: group 3
* Biological: group 4


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed stage III or stage IV melanoma Tumor expression of Melan-A +/- Tyrosinase Human leukocyte antigen-A2 (HLA-A2) positive Exclusion Criteria: Clinically significant heart disease Serious illnesses, eg, serious infections requiring antibiotics, bleeding disorders or uncontrolled peptic ulcer, or seizure or central nervous system disorders History of immunodeficiency disease or autoimmune disease Coagulation or bleeding disorders

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: group 1<br>Melan-A analog peptide + CpG + Montanide | Biological: group 1<br>* Melan-A analog peptide + CpG + Montanide<br>|
| Experimental: group 2<br>Melan-A natural peptide + CpG + Montanide | Biological: group 2<br>* Melan-A natural peptide + CpG + Montanide<br>|
| Experimental: group 3<br>Melan-A natural peptide + Tyrosinase YMD peptide + CpG + Montanide | Biological: group 3<br>* Melan-A natural peptide + Tyrosinase YMD peptide + CpG + Montanide<br>|
| Experimental: group 4<br>Melan-A analog peptide + Tyrosinase YMD peptide + CpG + Montanide | Biological: group 4<br>* Melan-A analog peptide + Tyrosinase YMD peptide + CpG + Montanide<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Melan-A and Tyrosinase specific CD8+ T-cell reactivity will be measured by Tetramers and Elispot assays |  | Change from baseline in CD8 T-cells reactivity at day 375 | 
| Safety of vaccination will be assessed according to National Cancer Institute Common Toxicity Criteria (NCI CTC) scale |  | Change from baseline to day 375 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In patients with measurable disease, tumor response will be assessed radiologically |  | Change from baseline in tumor response at day 375 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunotherapy, Vaccination, Melanoma, Melan-A/Mart-1 peptide, Tyrosinase peptide, CpG, Montanide