Clinical trial NCT00112229: Immunotherapy of HLA-A2 Positive Stage III/IV Melanoma Patients
Official title: Immunotherapy of HLA-A2 Positive Stage III/IV Melanoma Patients With CpG7909, Tumor Antigenic Peptides and Montanide
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Melanoma
Keywords: Immunotherapy
Vaccination
Melanoma
Melan-A/Mart-1 peptide
Tyrosinase peptide
CpG
Montanide
Lead sponsor: Centre Hospitalier Universitaire Vaudois
Sponsor class: OTHER
Collaborators: name: Ludwig Institute for Cancer Research
First posted: 2005-06-01
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Melan-A and Tyrosinase specific CD8+ T-cell reactivity will be measured by Tetramers and Elispot assays
timeFrame: Change from baseline in CD8 T-cells reactivity at day 375
measure: Safety of vaccination will be assessed according to National Cancer Institute Common Toxicity Criteria (NCI CTC) scale
timeFrame: Change from baseline to day 375
Secondary outcomes:
measure: In patients with measurable disease, tumor response will be assessed radiologically
timeFrame: Change from baseline in tumor response at day 375
Other outcomes:
Locations:
city: Lausanne
country: Switzerland
facility: Ludwig Institute for Cancer Research + Multidisciplinary Oncology Center at the Centre Hospitalier Universitaire Vaudois
state: Vaud
Study officials:
affiliation: Ludwig Institute for Cancer Research
name: Olivier Michielin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Speiser DE, Lienard D, Rufer N, Rubio-Godoy V, Rimoldi D, Lejeune F, Krieg AM, Cerottini JC, Romero P. Rapid and strong human CD8+ T cell responses to vaccination with peptide, IFA, and CpG oligodeoxynucleotide 7909. J Clin Invest. 2005 Mar;115(3):739-46. doi: 10.1172/JCI23373.
citation: Baumgaertner P, Jandus C, Rivals JP, Derre L, Lovgren T, Baitsch L, Guillaume P, Luescher IF, Berthod G, Matter M, Rufer N, Michielin O, Speiser DE. Vaccination-induced functional competence of circulating human tumor-specific CD8 T-cells. Int J Cancer. 2012 Jun 1;130(11):2607-17. doi: 10.1002/ijc.26297. Epub 2011 Aug 24.