malignant melanoma
Conditions
Interventions
Stage III and IV melanoma patients will be vaccinated three times biweekly with
mature DC injected intradermally and intravenously loaded with mRNA encoding
tumor-associated antigens gp100 and tyros
Sponsors
Universitair Medisch Centrum Sint Radboud
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: For both stage III and IV melanoma - histologically documented evidence of melanoma - stage III or IV melanoma according to the 2001 AJCC criteria - HLA-A2.1 phenotype is required - melanoma expressing gp100 (compulsory) and tyrosinase (non-compulsory) - WHO performance status 0-1 (Karnofsky 100-70%) - life expectancy >3 months - age 18-70 years - no clinical signs or symptoms of CNS metastases - WBC >3.0×109/l, lymphocytes >0.8×109/l, platelets >100×109/l, serum crea-tinine <150 µmol/l, serum bilirubin <25 µmol/l - normal serum LDH (*450 U/l) - expected adequacy of follow-up - no pregnant or lactating women - written informed consent For stage III melanoma - interval since regional lymph node dissection is <2 months For stage IV melanoma - at least one unidimensional measurable target lesions according to RECIST, not previously irradiated, and limited tumor burden, according to the responsible physician
Exclusion criteria
Exclusion criteria: - prior chemotherapy, immunotherapy or radiotherapy <4 weeks prior to planned vaccination or presence of treatment-related toxicity - history of any second malignancy in the previous 5 years, with the exception of adequately treated basal cell carcinoma or carcinoma in situ of the cervix serious active infections, HbsAg or HIV positive or autoimmune diseases or organ allografts - concomitant use of immunosuppressive drugs - known allergy to shell fish (since it contains KLH) - rapidly progressive disease - any serious clinical condition that may interfere with the safe administration of DC
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective of the study is to investigate the immunogenicity and feasibility of combined chemotherapy-DC vaccination. Immunologically responding patients are defined as: T cells isolated from vaccine challenged sites (DTH) that can be expanded and: 1) express T cell receptors specific for the vaccine, 2) show effector functions measured by IFNg secretion or cytolytic activity against tumor antigen expressing target cells. Immunologically non-responding patients are defined as: No T cells, or T cells isolated from vaccine challenged sites (DTH) that cannot be expanded, or T cells that can be expanded but do not recognize tumor antigens, or can recognize tumor antigens but do not display T effector functions i.e. lysis of tumor cell targets or release of IFNg. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary objective is to investigate the toxicity and clinical responses upon DC immunochemotherapy. Toxicity will be assessed using the Clinical Toxicity Criteria NCI CTC version 3.0. Tumor evaluation will be performed at baseline and every 3 months until progression according to modified RECIST criteria [30]. Clinically responding stage IV patients are defined as: patients with an objective complete or partial response, or disease stabilization for at least 4 months duration. Clinically non-responding stage IV patients are defined as: patients with progressive disease or stabilization for less than 4 months. Progression-free an overall survival will be documented as best response. In stage III patients the disease free survival will be documented. Furthermore, the effect of cisplatin on immune inhibitory molecules on peripheral blood and on tumor material will be investigated. | — |
Countries
Netherlands
Outcome results
None listed