Immunochemotherapy: Do platin-based chemotherapeutics enhance dendritic cell vaccine efficay in melanoma patients?

Completed

Conditions: malignant melanoma
10040900

Registration Number: NL-OMON36238

Lead Sponsor: niversitair Medisch Centrum Sint Radboud

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 54

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

- 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

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary objective of the study is to investigate the immunogenicity and<br /><br>feasibility of combined chemotherapy-DC vaccination.<br /><br>Immunologically responding patients are defined as: T cells isolated from<br /><br>vaccine challenged sites (DTH) that can be expanded and: 1) express T cell<br /><br>receptors specific for the vaccine, 2) show effector functions measured by IFNg<br /><br>secretion or cytolytic activity against tumor antigen expressing target cells.<br /><br>Immunologically non-responding patients are defined as: No T cells, or T cells<br /><br>isolated from vaccine challenged sites (DTH) that cannot be expanded, or T<br /><br>cells that can be expanded but do not recognize tumor antigens, or can<br /><br>recognize tumor antigens but do not display T effector functions i.e. lysis of<br /><br>tumor cell targets or release of IFNg.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>The secondary objective is to investigate the toxicity and clinical responses<br /><br>upon DC immunochemotherapy. Toxicity will be assessed using the Clinical<br /><br>Toxicity Criteria NCI CTC version 3.0. Tumor evaluation will be performed at<br /><br>baseline and every 3 months until progression according to modified RECIST<br /><br>criteria [30].<br /><br>Clinically responding stage IV patients are defined as: patients with an<br /><br>objective complete or partial response, or disease stabilization for at least 4<br /><br>months duration.<br /><br>Clinically non-responding stage IV patients are defined as: patients with<br /><br>progressive disease or stabilization for less than 4 months. Progression-free<br /><br>an overall survival will be documented as best response. In stage III patients<br /><br>the disease free survival will be documented.<br /><br>Furthermore, the effect of cisplatin on immune inhibitory molecules on<br /><br>peripheral blood and on tumor material will be investigated.</p><br>

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