Neoepitope-based Personalized Vaccine Approach in Pediatric Patients With Recurrent Brain Tumors
Status:
Withdrawn
Trial end date:
2026-02-28
Target enrollment:
Participant gender:
Summary
The early clinical development paradigm for chemotherapeutic agents has significantly
influenced the development of therapeutic cancer vaccines. However, there are major
differences between these two classes of therapeutics that have important implications for
early clinical development. Specifically, the phase 1 concept of dose escalation to find a
maximum-tolerated dose does not apply to most therapeutic cancer vaccines. Most therapeutic
cancer vaccines are associated with minimal toxicity at a range that is feasible to
manufacture or administer, and there is little reason to believe that the maximum-tolerated
dose is the most effective dose.
In a recent article from the biostatistics literature, Simon et al. write that "the initial
clinical trial of many new vaccines will not be a toxicity or dose-ranging trial but rather
will involve administration of a fixed dose of vaccine … in most cases the dose selected will
be based on preclinical findings or practical considerations. Using several dose levels in
the initial study to find the minimal active dose or to characterize the dose-activity
relationship is generally not realistic".
Consistent with these recommendations, the general philosophy of the phase 1 clinical trial
is to facilitate a prompt preliminary evaluation of the safety and immunogenicity of the
personalized synthetic long peptide vaccine strategy. The proposed clinical trial will test a
fixed dose of vaccine. There is considerable experience with the synthetic long peptide
vaccine platform. The synthetic long peptide vaccine platform has an excellent safety
profile, and the optimal dose appears to be based on practical considerations (solubility of
the peptide). The dose to be tested in the proposed clinical trial is consistent with other
similar cancer vaccine trials that have been recently completed or are currently ongoing. The
sample size (n=10-20) will provide a reasonably reliable estimate of the safety and
immunogenicity of the vaccine.