E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Our study population consists of HLA-A2.1 positive melanoma patients, with proven expression of melanoma associated tumor antigens gp100 and tyrosinase. Melanoma patients with regional lymph node metastasis in whom a radical lymph node dissection is planned or performed within 2 months of inclusion in this study (further referred to as stage III) and melanoma patients with measurable distant metastases (further referred to as stage IV) will be included. |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to investigate the toxicity of TLR-DC by dose escalation of DC numbers. |
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E.2.2 | Secondary objectives of the trial |
Secondary study endpoints are: (a) The migratory capacity of the TLR-ligand matured DC. (b) The activation of immune cells in vivo. (c) The immunological response induced with TLR-ligand matured DC loaded with mRNA encoding melanoma-associated tumor antigens (gp100 and tyrosinase). (d) The clinical efficacy of vaccination with TLR-ligand matured DC.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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, or radical lymph node dissection is planned 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 |
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objectives of the study are to investigate the toxicity of TLR-DC by dose escalation of DC numbers in part I, and to investigate immunological responses upon TLR-DC vaccination in part II and III of the study. Immunological responses are: (a) The migratory capacity of the TLR-ligand matured DC in vivo. (b) The activation of immune cells in vivo. (c) The immunological response induced with TLR-ligand matured DC loaded with mRNA encoding melanoma-associated tumor antigens (gp100 and tyrosinase). Safety and clinical efficacy are secondary objectives. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
treatment with mRNA-electroporated cytokine matured DC |
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E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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After the last visit of the last subject undergoing the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |