Active Specific Intranodal Immunotherapy of Recombinant Vaccinia Virus in Locally Advanced to Metastatic Melanoma
The purpose of this study is to assess intranodal immunotherapy in locally advanced to metastatic melanoma patients (American Joint Committee on Cancer [AJCC] stages IIb to IV).
For this, the investigators capitalize on their previous melanoma clinical trial (published by Zajac P et al in Human Gene Ther 2003) and take advantage of a proprietary recombinant vaccinia virus (replication inactivated) expressing 5 minigenes: 3 melanoma associated antigens and 2 costimulatory molecules. Immunization with the recombinant vaccinia virus is followed by 3 boosts with soluble, synthetic melanoma associated antigens.
The patients are immunized intranodally (groin lymph node) under ultrasonographic guidance in an outpatient clinic. The protocol foresees 2 cycles of immunotherapy for alternate weeks and lasts 15 weeks.
Genetic: Intranodal immunization with a recombinant vaccinia virus expressing 5 transgenes
Biological: Intranodal booster immunizations with synthetic melanoma associated epitopes
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Active Specific Intranodal Immunotherapy With a Recombinant Vaccinia Virus Expressing Three Melanoma Associated Epitopes and Two Costimulatory Molecules, Followed by Immunization With Synthetic Melanoma Associated Epitopes. A Phase I/II Trial in Patients With Stages IIb to IV Melanoma|
- Safety evaluation
- Clinical response
- Immune response assessment
- Survival (disease-free survival [DFS], overall survival [OS])
- Dose adaptation
|Study Start Date:||November 2002|
|Study Completion Date:||December 2008|
|Primary Completion Date:||July 2007 (Final data collection date for primary outcome measure)|
The investigators have conducted a phase I/II clinical trial based on the intradermal administration to stage III/IV melanoma patients of a recombinant vaccinia virus encoding tumor associated antigens and costimulatory epitopes for the priming of immune responses, followed by boosts with corresponding synthetic peptides (Zajac P et al in Human Gene Ther 2003). Specific cytotoxic T cells could be induced in a majority of patients following priming, but sustained responsiveness could not be maintained by peptide boosting on a long term basis. Emerging evidence supports the notion that expansion of specific T cells requires trafficking of antigen presenting cells loaded with specific determinants to lymphatic nodes, as induced, among others, by pro-inflammatory stimuli. Therefore, we now adopt the intranodal injection of the immunogenic formulations. As for the former melanoma active specific immunotherapy trial, GM-CSF is used as a supporting cytokine. The epitopes considered are expressed, either all or some of them, in over 90% of the melanomas in Western countries; namely, we immunize with Mart-1/Melan-A epitope 27-35, Gp-100 epitope 280-288 and tyrosinase epitope 1-9. As a consequence, HLA-A2 positivity is mandatory for inclusion in the trial. The 2 costimulatory molecules expressed by cells infected with our replication-incompetent recombinant vaccinia virus are B7.1 (CD80) and B7.2 (CD86).
Please refer to this study by its ClinicalTrials.gov identifier: NCT00116597
|University Hospital Basel|
|Basel, Switzerland, 4031|
|Principal Investigator:||Michel Adamina, M.D.||University Hospital, Basel, Switzerland|
|Study Chair:||Daniel Oertli, M.D.||University Hospital, Basel, Switzerland|
|Study Director:||Michael Heberer, M.D.||University Hospital, Basel, Switzerland|
|Principal Investigator:||Giulio C Spagnoli, M.D.||University Hospital, Basel, Switzerland|
|Principal Investigator:||Walter R Marti, M.D.||University Hospital, Basel, Switzerland|