E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
In this study our primary objective is to induce or enhance an immune response to tumor antigens in Lynch syndrome mutation carriers (with and without colorectal adenomas or carcinomas) and patients with sporadic colorectal cancer (CRC) showing microsatellite instability (MSI-high), the hallmark of MMR dysfunction, and test the hypothesis that DC vaccination might be effective as prophylactic treatment in Hereditary Non-Polyposis Colorectal Cancer (HNPCC) or Lynch syndrome mutation carriers. |
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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 safety and feasibility of vaccination with frameshift-derived neoantigen-loaded DC. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to evaluate whether peptide-loaded DC can induce or enhance an immune response to tumor-associated antigen CEA and specific frameshift-derived neoantigens in the study population and the pathological and or clinical responses, e.g. disease-free survival, determined according to the standard protocol.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• histologically documented evidence of CRC (group I) and Lynch syndrome carrier without signs of disease (group II) • HLA-A2.1 phenotype is required • MSI high tumor • 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 • WHO performance status 0-1 (Karnofsky 100-70%) • age 18-75 years • expected adequacy of follow-up • written informed consent |
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E.4 | Principal exclusion criteria |
• history of malignancy in the past 5 years with the exception of adequately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix • serious active infections, HbsAg or HIV positive (test only in case of high risk or clinical suspicion) • autoimmune diseases or organ allografts • concomitant use of immunosuppressive drugs • known allergy to shell fish • pregnant or lactating women
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E.5 End points |
E.5.1 | Primary end point(s) |
The first objective of this study is to evaluate safety and feasibility of vaccination with frameshift-derived neoantigen-loaded DC of CRC patients, who group I: are known to carry a germline MMR-gene mutation (Lynch syndrome patients) and patients with an MSI-positive CRC and yet unknown of negative MMR-gene mutation status and group II: persons who are known to be carrier of a germline MMR-gene mutation with no signs of disease yet. |
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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 | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
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 | No |
E.8.1.1 | Randomised | No |
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 | No |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |