Dendritic cell vaccination in patients with Lynch Syndrome or colorectal cancer with MSI - DC vaccination in lynch syndrome patients

Phase 1

Conditions: 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.

Registration Number: EUCTR2008-005584-33-NL

Lead Sponsor: Radboud University Nijmegen Medical Centre

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 25

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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of the study is to investigate the safety and feasibility of vaccination with frameshift-derived neoantigen-loaded DC.;Secondary Objective: 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.<br><br>;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.

Secondary Outcome Measures