The primary objective is to assess the effect of vaccination with neopeptide-loaded dendritic cells on disease-free survival (DFS) compared to placebo in LS subjects who are known to be carrier of a germline MMR-gene mutation with no signs of disease.
A phase III, multicentre, randomised, double-blind, placebo-controlled trial evaluating disease-free survival after vaccination with with neopeptide-loaded dendritic cells or placebo in LS subjects aged 35-75 who are confirmed to carry a germline MMR-gene mutation in MLH1, MSH2 or MSH6 without clinical signs of disease. Participants will be treated for 6 months + 4 weeks, with an additional maximum follow-up of 51.5 months (total study duration 58.5 months).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
372
Subjects in the DC vaccination arm will receive a maximum of 2 cycles each consisting of 3 DC injections intranodally (3-7x10\^6 DC)
Subjects in the placeb vaccination arm will receive a maximum of 2 cycles each consisting of 3 placebo injections intranodally (3-7x10\^6 DC)
Radboudumc
Nijmegen, Gelderland, Netherlands
Disease-free survival after DC vaccination or placebo
Defined as time between 1st vaccination until development of mismatch-repair deficient colorectal adenoma, any Lynch-related carcinoma in situ or Lynch-related carcinoma, Lynch-related death, or until follow-up ends, whichever occurs first.
Time frame: 58.5 months
Number of participants with Treatment-Related adverse events as assessed by CTCAE v5.0 (Safety)
Time frame: 36 months
Quality of Life Questionnaires
To evaluate whether LS subjects quality of life differs between DC vaccinated and placebo vaccinated groups. Defined as patient's self-perceived physical, psychological and social well-being in relation to their health status, assessed using questionnaires.
Time frame: baseline, week 3, week 28, month 12, month 24, month 36, month 48
To assess whether neoantigen-specific T cells are induced by the DC vaccine (immunogenicity).
Immunogenicity will be assessed by the percentage of participants showing a neo-antigen-specific T cell response, defined by the expansion of T cells that recognize tumor antigens and demonstrate effector functions. Non-responders are those with no T cell expansion or insufficient immune activity.
Time frame: 36 months
Health economic aspects including QALY
The primary objective of the analysis is to determine the cost-effectiveness of DC vaccination compared with standard surveillance in patients with LS, expressed as cost per quality-adjusted life year (QALY) gained and incremental net monetary benefit (iNMB) from a societal perspective, over both the trial timeframe (empirical) and the long term timeframe (modelling).
Time frame: 58.5 months
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